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The factors like, hydrophobic chain size in the amphiphilic molecule, amphiphiles concentration, solvent system and temperature, affects the micelle formation [ ]. The micelle assembly creation starts when minimum concentration known as the critical micelle concentration CMC is reached by the amphiphilic molecules [ ].
At lower concentrations, the amphiphilic molecules are indeed small and occur independently [ ]. Drugs are loaded within polymeric micelles by three common methodologies such as direct dissolution process, solvent evaporation process, and the dialysis process. As of the direct dissolution process, the copolymer and the drugs combine with each other by themselves in the water medium and forms a drug loaded with the micelles. While in the solvent evaporation process, the copolymer and the intended drug is dissolved using a volatile organic solvent and finally, in case of the dialysis process, both the drug in solution and the copolymer in the organic solvent are combined in the dialysis bag and then dialyzed with the formation of the micelle [ ].
The targeting of the drugs using different polymeric micelles as established by various mechanism of action including the boosted penetrability and the holding effect stimuli; complexing of a definite aiming ligand molecule to the surface of the micelle; or by combination of the monoclonal antibodies to the micelle corona [ ]. Polymeric micelles are reported to be applicable for both drug delivery against cancer [ ] and also for ocular drug delivery [ ] as shown in Fig.
In the work by Li et al. This micellar formulation ominously repressed the cell proliferation, attachment and relocation in comparison to the free drugs [ ]. The polymeric micelles is habitually get into the rear eye tissues through the transcleral pathway after relevant applications Fig. Polymeric micelles used for reaching the posterior ocular tissues via the transcleral pathway after topical application. Dendrimers are highly bifurcated, monodisperse, well-defined and three-dimensional structures.
They are globular-shaped and their surface is functionalized easily in a controlled way, which makes these structures excellent candidates as drug delivery agents [ , , ].
Dendrimers can be synthesized by means of two approaches: The first one is the different route in which the dendrimer starts formation from its core and then it is extended outwards and the second is the convergent one, starts from the outside of the dendrimer [ ]. Dendrimers are grouped into several kinds according to their functionalization moieties: PAMAM, PPI, liquid crystalline, core—shell, chiral, peptide, glycodendrimers and PAMAMOS, being PAMAM, the most studied for oral drug delivery because it is water soluble and it can pass through the epithelial tissue boosting their transfer via the paracellular pathway [ ].
Dendrimers are limited in their clinical applications because of the presence of amine groups. These groups are positively charged or cationic which makes them toxic, hence dendrimers are usually modified in order to reduce this toxicity issue or to eliminate it.
Drug loading in dendrimers is performed via the following mechanisms: Simple encapsulation, electrostatic interaction and covalent conjugation [ ]. Dendrimers have been developed for transdermal, oral, ocular, pulmonary and in targeted drug delivery [ ]. Jain et al. Similarly, Kaur et al. The in vitro studies on them showed sustained release, increased cell uptake and low cytotoxicity on MCF-7 cell lines [ ].
Further, it has to be pointed out that the developed formulations, methotrexate MTX -loaded and folic acid-conjugated 5. Inorganic nanoparticles include silver, gold, iron oxide and silica nanoparticles are included. Studies focused on them are not as many as there are on other nanoparticle types discussed in this section although they show some potential applications. However, only few of the nanoparticles have been accepted for its clinical use, whereas the majority of them are still in the clinical trial stage.
Metal nanoparticles, silver and gold, have particular properties like SPR surface plasmon resonance , that liposomes, dendrimers, micelles do not possess. They showed several advantages such as good biocompatibility and versatility when it comes to surface functionalization. Studies on their drug delivery-related activity have not been able to clear out whether the particulate or ionized form is actually related to their toxicity, and even though two mechanisms have been proposed, namely paracellular transport and transcytosis, there is not enough information about their in vivo transport and uptake mechanism [ ].
Drugs can be conjugated to gold nanoparticles AuNPs surfaces via ionic or covalent bonding and physical absorption and they can deliver them and control their release through biological stimuli or light activation [ ]. Similarly in another study, the iron oxide nanoparticles were synthesized using laser pyrolysis method and were covered with Violamycine B1, and antracyclinic antibiotics and tested against the MCF-7 cells for its cytotoxicity and the anti-proliferation properties along with its comparison with the commercially available iron oxide nanoparticles [ ].
Nanocrystals are pure solid drug particles within nm range. A nanocrystals suspension in a marginal liquid medium is normally alleviated by addition of a surfactant agent known as nano-suspension. In this case, the dispersing medium are mostly water or any aqueous or non-aqueous media including liquid polyethylene glycol and oils [ , ].
The process by which nanocrystals are synthesized are divided into top-down and bottom-up approaches. The top-down approach includes, sono-crystallization, precipitation, high gravity controlled precipitation technology, multi-inlet vortex mixing techniques and limited impinging liquid jet precipitation technique [ ].
However, use of an organic solvent and its removal at the end makes this process quite expensive. The bottom-up approach involves, grinding procedures along with homogenization at higher pressure [ ]. Among all of the methods, milling, high pressure homogenization, and precipitation are the most used methods for the production of nanocrystals.
The mechanisms by which nanocrystals support the absorption of a drug to the system includes, enhancement of solubility, suspension rate and capacity to hold intestinal wall firmly [ ]. Ni et al. The nanoparticles were contrived for continuous release of the drug taking advantage of the swelling and muco-adhesive potential of the polymer. They found that inhalation efficacy might be conceded under the disease conditions, so more studies are needed to prove that this system has more potential [ ].
In addition, the modification and functionalization of these nanoparticles with specific functional groups allow them to bind to antibodies, drugs and other ligands, become these making these systems more promising in biomedical applications [ ]. Although the most extensively studied, metallic nanoparticles are gold, silver, iron and copper, a crescent interest has been exploited regarding other kinds of metallic nanoparticles, such as, zinc oxide, titanium oxide, platinum, selenium, gadolinium, palladium, cerium dioxide among others [ 35 , , ].
Quantum dots QDs are known as semiconductor nanocrystals with diameter range from 2 to 10 nm and their optical properties, such as absorbance and photoluminescence are size-dependent [ ]. In this sense, QDs are very appealing for multiplex imaging. In the medicine field QDs has been extensively studied as targeted drug delivery, sensors and bioimaging. A large number of studies regarding the applications of QDs as contrast agents for in vivo imaging is currently available in literature [ , , , ].
Han et al. This fluorophore was used to label bone marrow cells in vivo. The authors found that the fluorophore was able to diffuse in the entire bone marrow and label rare populations of cells, such as hematopoietic stem and progenitor cells [ ]. Shi et al. According to the authors the attachment of an anti-GPC3-antibody to the nanoplataform results in selective separation of Hep G2 hepatocellular carcinoma cells from infected blood samples [ ]. Regarding the controlled release, this behavior can be achieved via external stimulation by light, heat, radio frequency or magnetic fields [ , , ].
Olerile et al. The nanoparticles were spherical with higher encapsulation efficiency of paclitaxel The authors also found that the system was able to specifically target and detect H22 tumor cells [ ].
Cai et al. This nanocarrier was also evaluated for doxorubicin DOX sustained release. Polysaccharides and proteins are collectively called as natural biopolymers and are extracted from biological sources such as plants, animals, microorganisms and marine sources [ , ].
Protein-based nanoparticles are generally decomposable, metabolizable, and are easy to functionalize for its attachment to specific drugs and other targeting ligands. They are normally produced by using two different systems, a from water-soluble proteins like bovine and human serum albumin and b from insoluble ones like zein and gliadin [ ]. The protein based nanoparticles are chemically altered in order to combine targeting ligands that identify exact cells and tissues to promote and augment their targeting mechanism [ ].
Similarly, the polysaccharides are composed of sugar units monosaccharides linked through O-glycosidic bonds. The composition of these monomers as well as their biological source are able to confer to these polysaccharides, a series of specific physical—chemical properties [ , , ]. One of the main drawback of the use of polysaccharides in the nanomedicine field is its degradation oxidation characteristics at high temperatures above their melting point which are often required in industrial processes.
Besides, most of the polysaccharides are soluble in water, which limits their application in some fields of nanomedicine, such as tissue engineering [ , ]. However, techniques such as crosslinking of the polymer chains have been employed in order to guarantee stability of the polysaccharide chains, guaranteeing them stability in aqueous environments [ , ].
In Fig. The success of these biopolymers in nanomedicine and drug delivery is due to their versatility and specified properties such as since they can originate from soft gels, flexible fibers and hard shapes, so they can be porous or non-porous; they have great similarity with components of the extracellular matrix, which may be able to avoid immunological reactions [ , ].
Different sources of natural biopolymers to be used in nanomedicine applications. Natural biopolymers could be obtained from higher plants, animals, microorganisms and algae. There is not much literature related to these kind of nanoparticles, however, since they are generated from biocompatible compounds they are excellent candidates for their further development as drug delivery systems.
Yu et al. The nanoparticles considered as the drug transporters were tested for their loading capacity and release behaviors that could provide better bio-suitability, drug loading capacity, and well-ordered discharge mechanism [ ].
Currently, the scientific community is focusing on the studies related to the bioactive compounds, its chemical composition and pharmacological potential of various plant species, to produce innovative active ingredients that present relatively minor side effects than existing molecules [ 5 , ].
Plants are documented as a huge sources of natural compounds of medicinal importance since long time and still it holds ample of resources for the discovery of new and highly effective drugs. However, the discovery of active compounds through natural sources is associated with several issues because they originate from living beings whose metabolite composition changes in the presence of stress.
In this sense, the pharmaceutical industries have chosen to combine their efforts in the development of synthetic compounds [ , , ]. Nevertheless, the number of synthetic molecules that are actually marketed are going on decreasing day by day and thus research on the natural product based active compounds are again coming to the limelight in spite of its hurdles [ , ].
Most of the natural compounds of economic importance with medicinal potential that are already being marketed have been discovered in higher plants [ , ]. The composition and activity of many natural compounds have already been studied and established. The alkaloids, flavonoids, tannins, terpenes, saponins, steroids, phenolic compounds, among others, are the bioactive molecules found in plants. However in most of the cases, these compounds have low absorption capacity due to the absence of the ability to cross the lipid membranes because of its high molecular sizes, and thus resulting in reduced bioavailability and efficacy [ ].
The scientific development of nanotechnology can revolutionize the development of formulations based on natural products, bringing tools capable of solving the problems mentioned above that limits the application of these compounds in large scale in the nanomedicine [ 7 , ].
Utilization of nanotechnology techniques in the medical field has been extensively studied in the last few years [ , ]. Hence these can overcome these barriers and allow different compounds and mixtures to be used in the preparation of the same formulation. In addition, they can change the properties and behavior of a compound within the biological system [ 7 , ].
Also, there is evidence that the association of release systems with natural compounds may help to delay the development of drug resistance and therefore plays an important role in order to find new possibilities for the treatment of several diseases that have low response to treatment conventional approaches to modern medicine [ 7 , ].
The natural product based materials are of two categories, 1 which are targeted to specific location and released in the specific sites to treat a number of diseases [ 43 , ] and 2 which are mostly utilized in the synthesis process [ ].
Most of the research is intended for treatment against the cancer disease, since it is the foremost reason of death worldwide nowadays [ , ]. In case of the cancer disease, different organs of the body are affected, and therefore the need for the development of an alternative medicine to target the cancerous cells is the utmost priority among the modern researchers, however, a number of applications of nanomedicine to other ailments is also being worked on [ , ].
These delivery systems are categorized in terms of their surface charge, particle size, size dispersion, shape, stability, encapsulation potential and biological action which are further utilized as per their requirements [ 33 ]. Some examples of biological compounds obtained from higher plants and their uses in the nanomedicine field are described in Fig. Pharmaceutical industries have continuously sought the development and application of new technologies for the advancement and design of modern drugs, as well as the enhancement of existing ones [ 71 , ].
In this sense, the accelerated development of nanotechnology has driven the design of new formulations through different approaches, such as, driving the drug to the site of action nanopharmaceutics ; image and diagnosis nanodiagnostic , medical implants nanobiomaterials and the combination diagnosis and treatment of diseases nanotheranostics [ 71 , , ].
Examples of natural compounds extracted from higher plants used in nanomedicine aiming different approaches.
Some of these extracts are already being marketed, others are in clinical trials and others are being extensively studied by the scientific community.
Currently, many of the nanomedicines under development, are modified release systems for active ingredients AI that are already employed in the treatment of patients [ , ]. For this type of approach, it is evaluated whether the sustained release of these AIs modifies the pharmacokinetic profile and biodistribution.
This section is focused on berberine, curcumin, ellagic acid, resveratrol, curcumin and quercetin [ 8 ]. Some other compounds mentioned are doxorubicin, paclitaxel and vancomycin that also come from natural products.
Nanoparticles have been synthesized using natural products. For example, metallic, metal oxide and sulfides nanoparticles have been reported to be synthesized using various microorganisms including bacteria, fungi, algae, yeast and so on [ ] or plant extracts [ ].
For the first approach, the microorganism that aids the synthesis procedure is prepared in the adequate growth medium and then mixed with a metal precursor in solution and left for incubation to form the nanoparticles either intracellularly or extracellularly [ , , ].
As for the second approach, the plant extract is prepared and mixed afterwards with the metal precursor in solution and incubated further at room temperature or boiling temperature for a definite time or exposed to light as an external stimulus to initiate the synthesis of nanoparticles [ ].
Presently, these natural product based materials are considered as the key ingredients in the preparation and processing of new nano-formulations because they have interesting characteristics, such as being biodegradable, biocompatible, availability, being renewable and presenting low toxicity [ , , ].
In addition to the aforementioned properties, biomaterials are, for the most part, capable of undergoing chemical modifications, guaranteeing them unique and desirable properties for is potential uses in the field of nanomedicine [ 45 , ]. Gold, silver, cadmium sulfide and titanium dioxide of different morphological characteristics have been synthesized using a number of bacteria namely Escherichia coli , Pseudomonas aeruginosa , Bacillus subtilis and Klebsiella pneumoniae [ ].
These nanoparticles, especially the silver nanoparticles have been abundantly studied in vitro for their antibacterial, antifungal, and cytotoxicity potential due to their higher potential among all metal nanoparticles [ , ]. In the event of microorganism mediated nanoparticle synthesis, maximum research is focused on the way that microorganisms reduce metal precursors and generate the nanoparticles.
For instance, Rahimi et al. Similarly, Ali et al. Further, Malapermal et al. Likewise, Sankar et al. Besides the use of microorganism, our group has synthesized silver, gold and iron oxide nanoparticles using various food waste materials such as extracts of Zea mays leaves [ , ], onion peel extract [ ], silky hairs of Zea mays [ ], outer peel of fruit of Cucumis melo and Prunus persica [ ], outer peel of Prunus persica [ ] and the rind extract of watermelon [ ], etc.
For drug delivery purposes, the most commonly studied nanocarriers are crystal nanoparticles, liposomes, micelles, polymeric nanoparticles, solid lipid nanoparticles, superparamagnetic iron oxide nanoparticles and dendrimers [ , , ]. All of these nanocarriers are formulated for natural product based drug delivery.
For applications in cancer treatment, Gupta et al. The authors concluded that the nanoparticle loaded drug exhibited better activity with sustained release, high cell uptake and reduced hemolytic toxicity compared with pure Paclitaxel [ ].
Berberine is an alkaloid from the barberry plant. Chang et al. Aldawsari and Hosny [ ] synthesized ellagic acid-SLNs to encapsulate Vancomycin a glycopeptide antibiotic produced in the cultures of Amycolatopsis orientalis.
Further, its in vivo tests were performed on rabbits and the results indicated that the ellagic acid prevented the formation of free oxygen radicals and their clearance radicals, thus preventing damages and promoting repair [ ]. Quercetin is a polyphenol that belongs to the flavonoid group, it can be found in citrus fruits and vegetables and it has antioxidant properties.
In a study by Dian et al. Daunorubicin is a natural product derived from a number of different wild type strains of Streptomyces , doxorubicin DOX is a hydrolated version of it used in chemotherapy [ ].
Spillmann et al. Perylene was used as a chromophore to track the particles and to encapsulate agents aimed for intracellular delivery [ ]. Purama et al. They concluded that the dendritic structure selectively enters the highly permeable portion of the affected cells without disturbing the healthy tissues thereby making more convenient for its application in the biomedical field [ ].
Folate- functionalized superparamagnetic iron oxide nanoparticles developed previously for liver cancer cure are also been used for the delivery of Doxil a form of doxorubicin which was the first FDA-approved nano-drug in [ ]. The in vivo studies in rabbits and rats showed a two- and fourfold decrease compared with Doxil alone while folate aided and enhanced specific targeting [ ].
Liposomes are the nanostructures that have been studied the most, and they have been used in several formulations for the delivery of natural products like resveratrol [ ]. Curcumin, a polyphenolic compound obtained from turmeric, have been reported to be utilized in the cure of cancers including the breast, bone, cervices, liver, lung, and prostate [ ]. Liposomal curcumin formulations have been developed for the treatment of cancer [ , ].
Cheng et al. Over all, it can be said that the sustained release systems of naturally occurring therapeutic compounds present themselves as a key tools for improving the biological activity of these compounds as well as minimizing their limitations by providing new alternatives for the cure of chronic and terminal diseases [ 8 , ]. Some of nanostructure-based materials covered in this section have already been approved by the FDA.
Bobo et al. In the current medical nanotechnology scenario, there are 51 products based on this technology [ , , , ] which are currently being applied in clinical practice Table 2. Notably, such nanomedicines are primarily developed for drugs, which have low aqueous solubility and high toxicity, and these nanoformulations are often capable of reducing the toxicity while increasing the pharmacokinetic properties of the drug in question.
According to a recent review by Caster et al. Among these nanomaterials that are in phase of study, 18 are directed to chemotherapeutics; 15 are intended for antimicrobial agents; 28 are for different medical applications and psychological diseases, autoimmune conditions and many others and 30 are aimed at nucleic acid based therapies [ ].
Nanotechnology has dynamically developed in recent years, and all countries, whether developed or not, are increasing their investments in research and development in this field.
However, researchers who work with practical applications of the nano-drugs deal with high levels of uncertainties, such as a framing a clear definition of these products; characterization of these nanomaterials in relation to safety and toxicity; and the lack of effective regulation. Although the list of approved nanomedicine is quite extensive, the insufficiency of specific regulatory guidelines for the development and characterization of these nanomaterials end up hampering its clinical potential [ ].
As a strategy for the lack of regulation of nanomedicines and nano drug delivery system; the safety assessment and the toxicity and compatibility of these are performed based on the regulations used by the FDA for conventional drugs. After gaining the status of a new research drug Investigational New Drug, IND by the FDA, nanomedicines, nano-drug delivery systems begin the clinical trials phase to investigate their safety and efficacy in humans.
These clinical trials are divided into three phases: phase 1 mainly assesses safety ; phase 2 mainly evaluates efficacy and phase 3 safety, efficacy and dosage are evaluated. After approval in these three phases the IND can be filed by the FDA to request endorsement of the new nanomedicine or nano drug delivery systems.
However, this approach to nanomedicine regulation has been extensively questioned [ , , ]. Due to the rapid development of nanotechnology as well as its potential use of nanomedicine, a reformed and more integrated regulatory approach is urgently required.
In this regard, country governments must come together to develop new protocols that must be specific and sufficiently rigorous to address any safety concerns, thus ensuring the release of safe and beneficial nanomedicine for patients [ , , ]. The science of nanomedicine is currently among the most fascinating areas of research.
A lot of research in this field in the last two decades has already led to the filling of patents and completion of several dozens of clinical trials [ ]. As outlined in the various sections above, cancer appears to be the best example of diseases where both its diagnosis and therapy have benefited from nonmedical technologies. The examples of nanoparticles showed in this communications are not uniform in their size, with some truly measuring in nanometers while others are measured in sub-micrometers over nm.
More research on materials with more consistent uniformity and drug loading and release capacity would be the further area of research.
Considerable amount of progress in the use of metals-based nanoparticles for diagnostic purposes has also been addressed in this review. The application of these metals including gold and silver both in diagnosis and therapy is an area of research that could potentially lead to wider application of nanomedicines in the future. One major enthusiasm in this direction includes the gold-nanoparticles that appear to be well absorbed in soft tumour tissues and making the tumour susceptible to radiation e.
This attributes to the field being a new area of science with only two decades of real research on the subject and many key fundamental attributes still being unknown. The fundamental markers of diseased tissues including key biological markers that allow absolute targeting without altering the normal cellular process is one main future area of research.
Hence, understanding the molecular signatures of disease in the future will lead to advances in nanomedicine applications. Beyond what we have outlined in this review using the known nanoprobes and nanotheragnostics products, further research would be key for the wider application of nanomedicine. Numerous studies in nanomedicine areas are centered in biomaterials and formulation studies that appear to be the initial stages of the biomedicine applications. Valuable data in potential application as drug therapeutic and diagnosis studies will come from animal studies and multidisciplinary researches that requires significant amount of time and research resources.
With the growing global trend to look for more precise medicines and diagnosis, the future for a more intelligent and multi-centered approach of nanomedicine and nano-drug delivery technology looks bright.
There has been lots of enthusiasm with the simplistic view of development of nanorobots and nanodevices that function in tissue diagnosis and repair mechanism with full external control mechanism. This has not yet been a reality and remains a futuristic research that perhaps could be attained by mankind in the very near future. As with their benefits, however, the potential risk of nanomedicines both to humans and the environment at large require long term study too.
Hence, proper impact analysis of the possible acute or chronic toxicity effects of new nanomaterials on humans and environment must be analyzed. As nanomedicines gain popularity, their affordability would be another area of research that needs more research input. Finally, the regulation of nanomedicines, as elaborated in the previous section will continue to evolve alongside the advances in nanomedicine applications. The present review discusses the recent advances in nanomedicines, including technological progresses in the delivery of old and new drugs as well as novel diagnostic methodologies.
A range of nano-dimensional materials, including nanorobots and nanosensors that are applicable to diagnose, precisely deliver to targets, sense or activate materials in live system have been outlined. Initially, the use of nanotechnology was largely based on enhancing the solubility, absorption, bioavailability, and controlled-release of drugs. Even though the discovery of nanodrugs deal with high levels of uncertainties, and the discovery of pharmacologically active compounds from natural sources is not a favored option today, as compared to some 50 years ago; hence enhancing the efficacy of known natural bioactive compounds through nanotechnology has become a common feature.
Good examples are the therapeutic application of nanotechnology for berberine, curcumin, ellagic acid, resveratrol, curcumin and quercetin. The efficacy of these natural products has greatly improved through the use of nanocarriers formulated with gold, silver, cadmium sulphide, and titanium dioxide polymeric nanoparticles together with solid lipid nanoparticles, crystal nanoparticles, liposomes, micelles, superparamagnetic iron oxide nanoparticles and dendrimers.
There has been a continued demand for novel natural biomaterials for their quality of being biodegradable, biocompatible, readily availability, renewable and low toxicity. Beyond identifying such polysaccharides and proteins natural biopolymers, research on making them more stable under industrial processing environment and biological matrix through techniques such as crosslinking is among the most advanced research area nowadays.
Polymeric nanoparticles nanocapsules and nanospheres synthesized through solvent evaporation, emulsion polymerization and surfactant-free emulsion polymerization have also been widely introduced. One of the great interest in the development of nanomedicine in recent years relates to the integration of therapy and diagnosis theranostic as exemplified by cancer as a disease model.
Good examples have been encapsulated such as, oleic acid-coated iron oxide nanoparticles for diagnostic applications through near-infrared; photodynamic detection of colorectal cancer using alginate and folic acid based chitosan nanoparticles; utilization of cathepsin B as metastatic processes fluorogenic peptide probes conjugated to glycol chitosan nanoparticles; iron oxide coated hyaluronic acid as a biopolymeric material in cancer therapy; and dextran among others.
Since the s, the list of FDA-approved nanotechnology-based products and clinical trials has staggeringly increased and include synthetic polymer particles; liposome formulations; micellar nanoparticles; protein nanoparticles; nanocrystals and many others often in combination with drugs or biologics. Thanks to advances in nanomedicine, our ability to diagnose diseases and even combining diagnosis with therapy has also became a reality.
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Biochem Biophys Res Commun. Molecular mapping of tumor heterogeneity on clinical tissue specimens with multiplexed quantum dots. Active targeting is achieved by incorporating antibody, ligands etc.
By active targeting liposomes directly go to the targeted organs or tissues, and release drug for a prolonged period of time, so that the normal cells are not affected and only the diseased cells are affected [ 21 ]. Targeted nanoliposomal drug delivery is more efficacious than the non-targeted drug delivery systems. C6-ceremide ligand induced nanoliposome used to treat the blood cancer directly targets the over expressed lukemic cells and decreases the high epxpression of survivin protein in leukemic cells [ 22 ].
The concept of long-circulating or sterically stabilized nanoliposomes is derived for novelibility of delivery systems which can circulate in the blood for a long period of time. Nanoliposomal formulations containing polyethylene glycol PEG alter the pharmacokinetic properties of various drug molecules leading to long elimination half-life [ 23 ].
Nanoliposomes are expected to bring lots of change in drug delivery in near future. Dendrimers are branched polymers, resembling the structure of a tree Figure 1. Dendrimers represent three dimensional highly branched polymeric macromolecules with the diameter varying from 2. It can be synthesized from both synthetic and natural monomers e. Two classes of dendrimers commonly used for biomedical applications are polyamidoamines and polypropyleneimines [ 24 ].
A dendrimer is typically symmetric around the core, and when sufficiently extended it often adopts a spheroidal three-dimensional morphology in water. A central core can be recognized in their structure with at least two identical chemical functionalities. Starting from those groups, repeated units of other molecules can originate with at least one junction of branching. The repetitions of chains and branching result in a series of radially concentric layers with increased crowding [ 25 ].
Branching of dendrimers depends on the synthesis processes. Low molecular weight drugs can be placed into the cavities within the dendrimer molecules and are temporarily immobilized there with hydrophobic forces, hydrogen and covalent bonds [ 26 ].
The two processes for the synthesis of dendrimers are divergent and convergent methods. In the divergent method dendrimer grows outwords from a multifunctional core molecule.
The core molecule reacts with monomer molecules containing one reactive and two dormant groups giving the first generation dendrimer. The convergent method is developed as a response to the weakness of the divergent synthesis. In the convergent approach, the dendrimer is constructed stepwise, starting from the end groups and progressing inwards. When the growing branched polymeric arms, called dendrons, are large enough, they are attached to a multifunctional core molecule.
The convergent method is relatively easy to purify the desired product and the occurrence of defects in the final structure is minimised [ 27 ].
Due to classical polymerization dendrimers have a negligible degree of polydispersity. They are random in nature and produce molecules of various sizes. The size of dendrimers can be carefully controlled during the process of synthesis of dendrimers. Scientists are focusing on newer approaches for speeding up the synthesis process by preassembly of oligomeric branches which can be linked together to reduce the number of synthesis steps involved and also increase the dendrimer yield [ 28 ].
Dendrimers are popularly used for transfer of genetic materials in cancer therapy or other viral diseases in different organs because of their monodisperisity, high density of functional groups, well-defined shape and multivalency.
Some other types of dendrimers are peptide dendrimers, glycodendrimers, polypropilimine dendrimers, Polyethyleneimine PEI dendrimers etc.
Nanoshells nm may be used for drug carrier of both imaging and therapy. Nanoshells consist of nanoparticles with a core of silica and a coating of thin metallic shell [ 29 ]. They can be targeted to a tissue by using immunological methods.
Nanoshells can also be embedded in a hydrogel polymer [ 30 ]. Nanoshells are currently being investigated for prevention of micrometastasis of tumors and also for the treatment of diabetes.
Nanoshells are useful for diagnostic purposes in whole blood immunoassays [ 31 ]. Fullerenes composed of carbon in the form of a hollow sphere or ellipsoid tube. Fullerenes are being investigated for drug transport of antiviral drugs, antibiotics and anticancer agents [ 32 ]. Fullerenes have the potential to stimulate host immune response and productions of fullerene specific antibodies. Soluble derivatives of fullerenes such as C60 have shown great utility as pharmaceutical agents.
Nanotubes are nanometer scale tube like structure and they are of different types like carbon nanotube, inorganic nanotube, DNA nanotube, membrane nanotube etc.
Carbon nanotubes can be made more soluble by incorporation of carboxylic or ammonium groups to their structures and can be used for the transport of peptides, nucleic acids and other drug molecules.
The ability of nanotubes to transport DNA across cell membrane is used in studies involving gene therapy. DNA can be attached to the tips of nanotubes or can be incorporated within the tubes [ 34 ]. Nanopores 20 nm in diameter consist of wafers with high density of pores which allow entry of oxygen, glucose and other chemicals such as insulin to pass through. Nanopores can be used as devices to protect transplanted tissues from the host immune system, at the same time, utilizing the benefit of transplantation [ 35 ].
Nanopores can also be employed in DNA sequencing. Nanopores are also being developed with an ability to differentiate purines from pyrimidines [ 36 ]. Quantum dots QD are tiny semiconductor nanocrystals type of particles generally no larger than 10 nanometers that can be made to fluoresce in different colours when stimulated by light. The biomolecule conjugation of the QD can be modulated to target various biomarkers [ 37 ].
They can be tagged with biomolecules and used as highly sensitive probes. QD can also be used for imaging of sentinel node in cancer patients for tumour staging and planning of therapy. This technology also outlines some early success in the detection and treatment of breast cancer [ 38 ]. QD may provide new insights into understanding the pathophysiology of cancer and real time imaging and screening of tumors. Bioconjugated QD are collections of variable sizes of nanoparticles embedded in tiny beads made of polymer material.
The new class of quantum dot conjugate contains an amphiphilic triblock copolymer layer for in vivo protection and multiple PEG molecules for improved biocompatibility and circulation, making it highly stable and able to produce bright signals. Another advantage is that quantum dot probes emitting at different wavelengths can be used together for imaging and tracking multiple tumor markers simultaneously, potentially increasing the specificity and sensitivity of cancer detection [ 40 ].
Recent progress in the surface chemistry of QD has expanded their use in biological applications, reduced their cytotoxicity and rendered quantum dots a powerful tool for the investigation of dinstinct cellular processes, like uptake, receptor trafficking and intracellular delivery. Another application of QD is for viral diagnosis. Rapid and sensitive diagnosis of Respiratory Syncytial Virus RSV is important for infection control and development of antiviral drugs.
Antibody-conjugated nanoparticles rapidly and sensitively detect RSV and estimate relative levels of surface protein expression. A major development is the use of dual-colour QD or fluorescence energy transfer nanobeads that can be simultaneously excited with a single light source [ 41 ].
QD linked to biological molecules, such as antibodies, have shown promise as a new tool for detecting and quantifying a wide variety of cancer-associated molecules. In the field of nanomedicine, QD can make a worthy contribution to the development of new diagnostic and delivery systems as they offer unique optical properties for highly sensitive detection and they are well defined in size and shape and can be modified with various targeting principles.
The blood brain barrier BBB is a structure formed by a complex system of endothelial cells, astroglia, pericytes, and perivascular mast cells, preventing the passage of most circulating cells and molecules [ 42 ]. The tightness of the BBB is attributed mainly to the vascular layer of brain capillary endothelial cells which are interconnected side-by-side by tight and adherens junctions.
Among the different nanodevices, nanosize drug delivery systems between 1 and nm work as a whole unit in terms of transport to cross BBB [ 43 ]. Nanosize brain drug delivery systems may promote the targeting ability of drug in brain and at the same time enhance the permeability of molecules through BBB. However crossing of BBB by the nano drug carriers will depend completely on the physicochemical and biomimetic features and does not depend on the chemical structure of drug, inside the nanoparticles [ 44 ].
Drug loaded nanoparticles with favourable biological properties include prolonging the residence time, decreasing toxicity and high ability of drug penetration into the deeper layers of the ocular structure and minimizing precorneal drug loss by the rapid tear fluid turnover [ 46 ].
Nanoparticles could target at cornea, retina and choroid by surficial applications and intravitreal injection. Nanocarrier based drug delivery is suitable in the case of the retina, as it has no lymph system, hence retinal neovascularisation and choroidal neovascularization have similar environments to that of solid tumors, and the EPR effect as available for solid nanoparticles in case of solid tumor may be also available for drug delivery targeted to eyes by nanoparticles [ 47 ].
Nanoparticles can deliver ocular drugs to the target sites for the treatment of various diseases such as glaucoma, corneal diseases, diabetic retinopathy etc. The uses of nanotechnology based drug delivery systems like nanosuspensions, SLNs and nanoliposomes have greater effect for ocular therapeutic efficacy [ 48 ].
Nanotechnology-based drug delivery is also very efficient in crossing membrane barriers, such as the blood retinal barrier in the eye. Contact lenses loaded with nanoparticles can be effective for topical administration of ophthalmic drugs. Drug loaded contact lenses can also provide continuous drug release because of slow diffusion of the drug molecules through the lens matrix. The soaked contact lenses also delivered drugs only for a period of few hours for some typical drugs [ 49 ].
The duration of drug delivery from contact lenses can be significantly increased if the drug is first entrapped in nanoformulations, such as nanoliposomes, nanoparticles, or microemulsions.
Such drug nanocarriers can then be dispersed throughout the contact lens material. The entrapment of drug in nanocarriers also prevents the interaction of drug with the polymerization mixture. This provides additional resistance to drug release, as the drug must first diffuse through the nanocarriers and penetrate the drug carrier surface to reach the contact lens matrix [ 50 ].
The ocular biodistribution of nanoparticles can provide insights into the bioavailability, cellular uptake, duration of drug action and toxicity. Factors such as particle size, composition, surface charge and mode of administration influence the biodistribution in the retinal structures and also their drainage from the ocular tissues [ 51 ].
The surface chemistry can also affect nanoparticle distribution. Positively charged nanoparticles can adhere to the anionic vitreous network components and aggregate within the vitreous network.
Posively charged nanoparticles can adhere to the anionic vitreous network components and aggregate within the vitreous humor [ 53 ].
Anionic nanoparticles were found to diffuse through the vitreous humor and could even penetrate the retinal layers to be taken up by Muller Cells [ 54 ]. Vitreous humor is regarded as the barrier for non-viral ocular gene therapy because of the strong interaction of conventional cationic nature of non-viral gene vectors with the anionic vitreous humor [ 53 ]. The cationic PEI nanoparticles aggregated within vitreous humor and were prevented from distributing to the retina by the vitreal barrier.
Cancer cells are more vulnerable than normal cells to the effect of chemotherapeutic agents and the most of the anticancer drugs can cause injury to the normal cells. Optimum dose and frequency are both important factors in the persistence of cancer cells during cancer chemotherapy [ 56 ]. Now attempts are focused on efforts to kill cancer cells by more specific targeting while sparing the normal cells.
Nanoparticulate delivery systems in cancer therapies provide better penetration of therapeutic and diagnostic substances within the cancerous tissue in comparison to conventional cancer therapies [ 57 ]. Nanoparticles are constructed to take advantages of fundamental cancer morphology and modes of development such as rapid proliferation of cells, antigen expression, and leaky tumor vasculature.
Nanoparticulate drug delivery systems are being developed to deliver smaller doses of chemotherapeutic agents in an effective form and control drug distribution within the body [ 58 ]. Nanocarriers can offer many advantages over free drugs in cancer chemotherapy such as they protect the drug from premature degradation, prevent drugs from prematurely interacting with the biological environment, enhance absorption of the drugs into a selected tissue solid tumour , control the pharmacokinetic and drug tissue distribution profile and improve intracellular penetration [ 59 ].
Nanoparticulate delivery systems utilize specific targeting agents for cancer cells minimizing the uptake of the anticancer agent by normal cells and enhance the entry and retention of the agent in tumor cells Figure 3 [ 60 ]. Nanocarriers may actively bind to the specific cancer cells by attaching targeting agents with the help of ligand molecules to the surface of the nanocarriers that bind to specific receptor antigens on the cell surface.
Nanocarriers will recognize and bind to target cells through ligand receptor interactions. It is even possible to increase the drug targeting efficacy with the help of antibodies by conjugating a therapeutic agent directly to it for targeted delivery [ 61 ]. Like receptor targeting, targeting of angiogenic factors also takes advantage of properties unique to cancer cells.
Anti-angiogenic treatment is the use of drugs or other substances to stop tumors from developing new blood vessels. In a study nanoparticles were formulated comprising a water-based core of Vickers microhardness sodium alginate, cellulose sulphate, and anti-angiogenic factors such as thrombospondin TSP -1 or TSP, crosslinked with dextran polyaldehyde with calcium chloride or conjugated to heparin sulphate with sodium chloride.
In addition bioluminescent agent, luciferase, or contrast agent, polymeric gadolinium was located within the polyanionic core [ 62 ] for drug targeting and detection. Similarly, many efforts are on for cancer cell targeting specifically with drug nanocarriers..
Thus the drug nanocarriers are of great hope for future cancer therapy. Schematic diagram of nanoparticle permeation and retention effect in normal and tumour tissues. Normal tissue vasculatures are lined by tight endothelial cells, hereby preventing nanoparticulate drug delivery system from escaping, whereas tumor tissue vasculatures are leaky and hyperpermeable allowing preferential accumulation of nanoparticles or nanoliposomes in the tumor interstial space by passive targeting.
Transfer of genetic material in nanocarriers may be an approach for the treatment of various genetic disorders such as diabetes mellitus, cystic fibrosis, alpha 1 antitrypsin deficiency and may more. A number of systemic diseases are caused by lack of enzymes factors that are due to missing or defective genes [ 63 ]. Previously gene therapy which was used to treat genetic disorders nowadays being contemplated as carrier systems which could be implanted for combating diseases other than genetic disorder like malignant form of cancer, heart diseases and nervous diseases [ 64 ].
Nanoliposomes can be used to deliver genetic materials into cells. Nanoliposomes incorporated with PEG and galactose target liver cells effectively due to their rapid uptake by liver Kupffer cells. Cationic nanoliposomes have been considered as potential non-viral human gene delivery system [ 65 ].
Also mixing cationic lipids with plasmid DNA leads to the formation of lipoplexes where the process is driven by electrostatic interactions [ 66 ]. The negatively charged genetic material e.
Plasmid liposome complexes can enter the disease cells by infusion with the plasma or endosome membrane. Allovectin-7 gene transfer product is composed of a plasmid containing the gene for the major histocompatibility complex antigene HLA-B7 with B2 microglobulin formulated with the cytofectin [ 67 ].
The nature of a composed lipid decides the unloading of the gene from nanoliposomes which enables control over the mode of release, doping of nanoliposomes with neutral lipids such as 1,2-Dioleoyl-sn-glycerophosphoethanolamine DOPE which helps in endosomal membrane fusion by recognizing and destabilizing the phospholipids in a flip flop manner which paves way for the liposomes to integrate in the membrane with the dissociation of nucleic acid into the cytoplasm [ 64 ].
Viral system based gene carrier had the ability to overcome the biological barriers in the body and then access to the host nucleus replicative machinery which resulted in the exploitations of the system for drug delivery using nanotechnology [ 64 ].
The development of a non-viral method for in vivo gene transfer was designed where the vector was packed into compact nanoparticles by successive additions of oppositely charged polyelectrolytes including an incorporation of ligands into the DNA-polyelectrolyte shells which were mixed with Pluronic F gel serving as a biodegradable adhesive to keep shells in contact with the targeted vessel [ 68 ].
A novel method of gene delivery is with viruses such as adeno associated virus AAV which have their virulent genes removed with lentiviruses, clearly showing their efficiency [ 64 ].
The viral nanoparticles VNPs consist of protein core which ranges in complexity from small capsid-protein homomers to larger protein-based heteromers capable of internalizing oligonucleotides and being enveloped by lipids.
Chemical modification process and genetic mutation provide the viral coat proteins with receptor binding domain that helps in cell specific targeting of VNPs [ 69 ]. VNPs can be genetically engineered by inserting amino acids for bioconjugation, peptide based affinity tags and peptides as targeting ligands for stimulation of immune response.
High sequence variability due to the influence of the immune system in viral life-cycles is often seen on the surface loops of viral capsid proteins. This variability makes the loops highly susceptible to insertion of foreign sequences. VP1, the major coat protein of viruses of Polyomaviridae family, when expressed in insect cells, yeast and Escherichia coli self-assembles as protein cages and shows natural affinity for a cell surface glycoprotein with a terminal a 2,3-linked N-acetylneuraminic acid and attaches to a4h1-integrin receptors [ 71 ].
Virus like particle VLPs constructed from the virus are used to deliver therapeutic genes to human fetal glial cells. Another technique Cell-docking involves attachment of antibodies to the surface of brain natriuretic peptide BNPs. Coupling reaction between murine polyoma-virus and antitumor antibody B3 yielded polyoma VLPs with 30 to 40 antibody fragments bound to the surface, allowing the modified VLPs to bind to the breast carcinoma cells with high efficiencies [ 72 ].
Advancement of nanosize drug delivery systems establishes a new paradigm in pharmaceutical field. Convergence of science and engineering leads a new era of hope where medicines will act with increase efficacy, high bioavailability and less toxicity. Several nanoscale drug delivery systems are currently in clinical trials and few of them are already commercially available.
Examples of such products are Abeicet for fungal infection , Doxil antineoplastic , Abraxane metastatic breast cancer , Emend antiemetic etc. Although nanocarriers have lots of advantages because of the unique properties they have, there are many clinical, toxicological and regulatory aspects which are the matters of concern too.
The biocompatibility of nanomaterials is of atmost importance because of the effect of the nanomaterials in the body ranging from cytotoxicity to hypersensitivity [ 8 ]. With the advancement of nanotechnology, the biological phenomenon such as host response to a specific nanomaterial should also be clinically transparent [ 9 ].
Therefore it is quite essential to introduce cost effective, better and safer nanobiomaterials which will provide efficient drug loading and controlled drug release of some challenging drug moieties for which there is no other suitable delivery available yet.
Nanoliposomes are well developed and presently possess the highest amount of clinical trials among other nanomaterials with some formulations currently in the market. This may be due to the fact that other materials have not been investigated for the same duration and are relatively newer in comparison. However polymer based nanomaterial, carbon nanotubes, gold nanoparticles etc. Genexol-PM is an example which was undergone recent clinical trial. Fungal infections associated with acute leukemia and for central line fungal infections, amphotericin B containing nanoliposomes are in phase IV clinical trial.
ThermoDox Doxorubicin loaded nanoliposome is currently in phase III trials for hepatocellular carcinoma. Similarly Caelyx, a doxorubicin HCl loaded nanoliposome that is pegylated, is currently in phase IV trials for ovarian neoplasms [ 7 ]. Some recent clinical trials are shown in Table 1. Ligand or antibody conjugated nanoformulation, bifunctional and multifunctional nanoparticles are the newer research approaches through which detection and treatment of cancerous cells can be achieved.
Nanomachines are also largely in the research-and-development phase, but some primitive molecular machines have been tested. An example is nanorobot which is capable of penetrating the various biological barriers of human body to identify the cancer cells.
Thus, nanodrug delivery systems have a leading role to play in nanomedicine in near future. Nanocarriers may lead to a solution to major unsolved medical problems which will aggressively enhance quality of life. Regulatory aspect: One of the main areas related to the safety aspects of drug-nanocarrier systems is to encourage academic organizations, industry and regulatory governmental agencies to establish convincing testing procedures on the safety aspects of the nanomaterials.
The global importance of trade for nanomaterials has established new international organizations, such as the International Council on Nanotechnology ICON , the International Organization for Standardization Geneva, Switzerland etc. Last few years several new technologies have been developed for the treatment of various diseases. The use of nanotechnology in developing nanocarriers for drug delivery is bringing lots of hope and enthusiasm in the field of drug delivery research.
Nanoscale drug delivery devices present some advantages which show higher intracellular uptake than the other conventional form of drug delivery systems. Nanocarriers can be conjugated with a ligand such as antibody to favor a targeted therapeutic approach. The empty virus capsids are also being tried to use for delivering drugs as a new therapeutic strategy.
Thus, nanoscale size drug delivery systems may revolutionize the entire drug therapy strategy and bring it to a new height in near future. However, toxicity concerns of the nanosize formulations should not be ignored. Full proof methods should be established to evaluate both the short-term and long-term toxicity analysis of the nanosize drug delivery systems.
Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution 3. Edited by Ali Demir Sezer. Impact of this chapter. Introduction Nanotechnology is a revolutionary field of micro manufacturing involving physical and chemical changes to produce nano-sized materials.
Nanoparticles Nanoparticles are submicron-sized polymeric colloidal particles with therapeutic agents of interest encapsulated or dispersed within their polymeric matrix or adsorbed or conjugated onto the surface.
Nanoliposomes Nanoliposomes are the nanosize vesicles made of bilayered phospholipid membranes generally unilamellar with an aqueous interior Figure 1 [ 17 ]. Dendrimers Dendrimers are branched polymers, resembling the structure of a tree Figure 1.
Nanoshells Nanoshells nm may be used for drug carrier of both imaging and therapy. Fullerenes and nanotubes Fullerenes composed of carbon in the form of a hollow sphere or ellipsoid tube. Nanopores Nanopores 20 nm in diameter consist of wafers with high density of pores which allow entry of oxygen, glucose and other chemicals such as insulin to pass through.
Quantum dots Quantum dots QD are tiny semiconductor nanocrystals type of particles generally no larger than 10 nanometers that can be made to fluoresce in different colours when stimulated by light. Nanotechnology for brain drug delivery The blood brain barrier BBB is a structure formed by a complex system of endothelial cells, astroglia, pericytes, and perivascular mast cells, preventing the passage of most circulating cells and molecules [ 42 ].
Nanosize drug carriers in ocular drug delivery Drug loaded nanoparticles with favourable biological properties include prolonging the residence time, decreasing toxicity and high ability of drug penetration into the deeper layers of the ocular structure and minimizing precorneal drug loss by the rapid tear fluid turnover [ 46 ].
Nanoparticle loaded contact lenses Contact lenses loaded with nanoparticles can be effective for topical administration of ophthalmic drugs. Biodistribution of nanoparticles in the retina The ocular biodistribution of nanoparticles can provide insights into the bioavailability, cellular uptake, duration of drug action and toxicity.
Nanoparticles in cancer Cancer cells are more vulnerable than normal cells to the effect of chemotherapeutic agents and the most of the anticancer drugs can cause injury to the normal cells. Gene delivery Transfer of genetic material in nanocarriers may be an approach for the treatment of various genetic disorders such as diabetes mellitus, cystic fibrosis, alpha 1 antitrypsin deficiency and may more.
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Nanoparticles in drug delivery: past, present and future. Adv Drug Delivery Rev. Panyam J, Labhasetwar V. Biodegradable nanoparticles for drug and gene delivery to cells and tissue.
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Colloids Surf B Biointerfaces. Preparation and in vitro evaluation of a pegylated nano-liposomal formulation containing docetaxel. Sci Pharm.
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Technological development such as the internet of things IoT and high-speed Internet connectivity is leading to the growth of wearable electronic devices. Clothes, glasses, and watches are some of the most common wearables , and they can be directly attached to human skin to collect physical, chemical, and biological signals generated by the body change or their surroundings. Day by day, technologies are widening remote health care monitoring and human-machine interfaces. Nanotech-based wearables come with sensors that are at par with diagnostics devices, can help detect various medical changes in the body, and can ultimately provide life-saving support.
Nanotech-based wearables are segmented as bio-integrated devices, wearable health care systems, soft robotics, and electronic skins. Nanotech-based wearables use the nanomaterials and nanocomposites such as carbon nanotubes CNT , silver nanowires, and graphene, which are integrated into clothing and accessories.
Nanotechnology is expected to reduce wearables size while retaining functional capabilities and distinctions. Currently, several of the key companies are actively working on Nanotech-based wearables. It aims to catch the biological inputs and sends alerts to doctors about congestive heart failure.
Nanowear received its third FDA k clearance in September and first software-only clearance as an end-to-end digital platform, allowing the company to market a software-as-a-medical service that uses standalone artificial intelligence AI and deep learning algorithms to perform remote diagnosis. Similarly, NanoEDGE is an interdisciplinary research project aiming at converging production techniques for functionalized electrodes with expertise in nanomaterial fabrication and characterization to produce multi-level sensors that can monitor health stats like electroencephalography EEG and electromyography EMG.
Due to intense innovation, technological transformation, and active participation of the tech giants, the Nanotech-based wearables electronics field has evolved rapidly during the past few years and is expected to grow significantly in the coming years as well. Owing to the rising investment and growing demand, several new players are expected to enter Healthcare Nanotechnology Market in the coming years.
Nanomedicine is a promising application in the healthcare field. Being expensive and high cost of development and difficulty in manufacturing are the key factors expected to hamper the growth of the Healthcare Nanotechnology Market.
Nanomedicine is bringing new possibilities to support the development of early diagnostic tools and better treatment options in the healthcare market. It is observed that more than active or recruiting clinical trials are currently focusing on different therapeutics and diagnostics use of nanomedicines.
Since the beginning of , nearly new clinical trials active or recruiting have been started, as reported in the National Library of Medicine US. The increasing investment, rising interest by the tech giants, and research activities in the Nanotechnology sector are providing momentum to nanomedicine growth. The ongoing innovation is expected to bring more exciting medical breakthroughs and overcome the existing challenge in treating complex diseases such as cancer, cardiovascular, neurodegenerative diseases, genetic disorders, and other illnesses.
Several nanomedicines and nanodiagnostics are already FDA-approved, and many more are in clinical trials and expected to hit the market in the near future. In the coming years, nanotechnology will significantly improve medical diagnostics and treatment scenarios which will be more effective and less expensive than the existing methods.
It is set to broaden the healthcare outcome for a large section of society by fulfilling unmet medical needs. Clinical Decision Support Systems CDSS is one of the most anticipated health technologies that tend to transform treatment dynamics and the healthcare market outlook.
With the ongoing development, the CDSS is expected to hold immense potential to bridge the gap between the available patient data and healthcare ex Sleep disorders or sleep-wake disorders are one of the major health burdens in today's time.
Sleep is a fundamental process in human life and well-being, and these disorders largely remain untreated or, more often, misdiagnosed as psychiatric problems. Sleep disorders affect and change the way that a person sleep The growth and development in the Digital health technologies, such as mobile health mHealth apps, electronic health records EHRs , electronic medical records EMRs , wearable devices, telehealth, and telemedicine, as well as personalized medicine, have immensely transformed the healthcare industry and its marke The American Society of Clinical Oncology is a platform that provides a global connection to researchers, pharma companies, and healthcare professions standing against cancer, finding a cure for it.
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Emerging Role of Digital Health in the Field of Oncology The growth and development in the Digital health technologies, such as mobile health mHealth apps, electronic health records EHRs , electronic medical records EMRs , wearable devices, telehealth, and telemedicine, as well as personalized medicine, have immensely transformed the healthcare industry and its marke Join Up Now! Subscribe Now! Where Women Healthcare Stands. ASCO Conference The American Society of Clinical Oncology is a platform that provides a global connection to researchers, pharma companies, and healthcare professions standing against cancer, finding a cure for it.
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Phenelzine Sulfate Nardil p. Both of the medicinal products have been applied in clinical practice for years however the combination of both has not been given for cancer therapy. The aim of the study is to investigate the effect of those two drugs together. Safety and efficacy will be assessed weekly for the period of 3 administration cycles. Abraxane administration is given weekly for the first 3 weeks of a 4-week period for 3 consecutive cycles.
Phenelzine sulfate will be given daily for 3 cycles. Study is divided in five cohort groups each will be given a progressively increasing dose of phenelzine sulfate. Abraxane Cmax 2. Abraxane Tmax 3. Abraxane Half-life 4. Abraxane AUC 5. Nardil Cmax 6. Nardil Tmax 7. Nardil Half-life 8. Nardil AUC 9. To investigate efficacy. To assess progression-free survival and overall survival of these patients. Nanoparticle albumin-bound rapamycin Interventions 1. Laboratory Biomarker Analysis 2.
Quality-of-Life Assessment Brief Summary This pilot study investigates clinical response to rapamycin administered to patients with advanced cancer and having abnormal genetic test results in a protein called mechanistic target of rapamycin mTOR.
Patients are given nanoparticle albumin-bound rapamycin, which may inhibit the growth of cancer cells by influencing the mTOR enzyme, required for cell growth. Primary Outcome Measures 1. Proportion of confirmed responses clinical benefit Secondary Outcome Measures 1. Incidence of adverse events 2. Relationship of adverse events to study treatment 3. Survival time 4. Time to disease progression Other Outcome Measures 1.
Incidence of adverse events grade 3 or 4 as a measure of safety and tolerability. Incidence of abnormal clinical laboratory values as a measure of safety and tolerability.
Incidence abnormal of electrocardiogram findings as a measure of safety and tolerability. Incidence of adverse events at the Maximum Tolerated Dose grade 3 or 4 5.
Incidence of abnormal lab values at the Maximum Tolerated Dose 6. Early signs of anti-tumor efficacy overall response rate 2. Early signs of anti-tumor efficacy duration of response IV. Maximally tolerated dose of Abraxane dose limiting toxicities Secondary Outcome Measures 1.
Surgical morbidity will be measured Dindo-Clavien classification 2. Maximum plasma concentration of Abraxane 3. Pharmacodynamics of Abraxane will be analyzed using tumor markers CA Pharmacodynamics PD of Abraxane will be analyzed by tumor biopsies 6.
Neutropenia neutrophil count 9. Decreased platelet count V. Assess the safety profile II. Determine the pharmacokinetic characteristics III. Determine the preliminary efficacy of the study drug combinations. Investigate potential biomarkers of efficacy Study design : Interventional, Non-randomized, Open label, Parallel assignment Study dates : Study start date: January 8, ; Study end date: February 12, Study Status : completed Arms : 1.
Maximum tolerated dose and recommended Phase II dose of ceritinib in combination with gemcitabine hydrochloride alone 2. Maximum tolerated dose and recommended Phase II dose of ceritinib in combination with gemcitabine hydrochloride and cisplatin 3.
Maximum tolerated dose and recommended Phase II dose of ceritinib in combination with gemcitabine hydrochloride and paclitaxel albumin-stabilized nanoparticle formulation Secondary Outcome Measures 1. Incidence of adverse events of Ceritinib in combination treatment with gemcitabine hydrochloride chemotherapy Safety profile based on event type, frequency, severity, time relationship, seriousness and relationship to study treatment.
Pharmacokinetics of Ceritinib and Gemcitabine hydrochloride combined: A population based pharmacokinetic model to estimate individual AUC or clearance of Ceritinib 3.
Pharmacokinetics of Ceritinib, Gemcitabine hydrochloride, and paclitaxel albumin-stabilized nanoparticle formulation; A population based pharmacokinetic model will be developed to estimate individual AUCs or CL of Ceritinib in combination with Gemcitabine hydrochloride and nab-Paclitaxel.
Pharmacokinetic characteristics of paclitaxel albumin-stabilized nanoparticle formulation, and cisplatin; A population based pharmacokinetic model will be developed to estimate individual AUCs or CL of Ceritinib in combination with Gemcitabine hydrochloride and Cisplatin. Progression free survival 6. Tumor biomarkers and levels of serum VI. Primary Outcome Measures Safety assessment to determine maximum tolerated dose by monitoring the development of adverse events and dose-limiting toxicity Secondary Outcome Measures Safety assessment by monitoring administration site reactions, abnormal lab values and adverse events VII.
Determine the progression-free survival of gemcitabine hydrochloride gemcitabine , cisplatin, and nab-paclitaxel in advanced, untreated biliary cancers. Determine the response rate and disease control rate II. Determine overall survival of gemcitabine, cisplatin, and nab-paclitaxel in advanced biliary cancers. Evaluate the toxicity of gemcitabine, cisplatin, and nab-paclitaxel in advanced biliary cancers. Drug: Nab-paclitaxel i. Other: Laboratory Biomarker Analysis, Correlative studies Brief Summary This study investigates the efficacy of the intervention drugs administered in patients with biliary cancers.
This trial studies the side effects and optimal dose of AGuIX when injected together with whole brain radiation therapy. The preliminary effectiveness of the combination of AGuIX and radiation therapy will be also assessed. MRI to assess intracranial progression-free survival 6.
Overall survival IX. Nab-paclitaxel i. Brief Summary The purpose of this study is to assess the safety and preliminary efficacy of the combination of drugs: CORT and nab-paclitaxel administered in patients with solid tumors. Objective response rate, progression free survival, overall survival 2.
Objective response rate, progression free survival, and overall survival in patients with GR-positive or GR negative solid tumors. Pharmacokinetics: exposure-response 4.
SOR 0. SOR 1. SOR 2. Incidence of treatment emergent adverse events Secondary Outcome Measures 1. Difference in total area of eligible lesion s in the treatment area 2.
Objective clinical response 3. Reduction in pain at the treatment area 4. Pharmacokinetic parameter — AUC 5. Pharmacokinetic parameter — Cmax 6. Pharmacokinetic parameter — Tmax XI. UV filtering agent and bioadhesive nanoparticles BNPs 2. Sham Comparator: A placebo strips with no UV filtering 4. Control, no agent applied. Brief Summary : Study assesses the safety, sun protection factor SPF characteristics, and the duration of protection. Primary Outcome Measures Skin Reaction assessed by examination evidence of irritation, inflammation, follicular occlusion.
To assess the safety of i. To verify intratumoral penetration of NU To verify the feasibility of administering NU as a standard treatment for recurrent glioblastoma multiforme or gliosarcoma.
Progression free survival and overall survival at 6 months; overall response rate. Experimental treatment NU Intervention : 1. Pharmacological Study Brief Summary : The aim of this study is to evaluate the safety of the administered drug, NU, via application of nucleic acids arranged on the surface of a small spherical gold nanoparticle in patients with recurrent glioblastoma multiforme or gliosarcoma. The researchers expect that targeting the Bcl2L12 gene with NU will stop cancer cells from growing.
Drug concentration in blood 2. Biodistribution of NU in tumor tissue concentration of particles in various parts of the tumors. Feasibility of administering NU as a standard treatment. Business Criteria for the Development of Drug Carriers During the manufacturing of drug forms, different methods should be considered. Transfer of Drug Carriers Synthesis Methods from Lab to Industry - Challenges Despite increased interest in nanodrugs in recent years, the transfer of methods to the market is still a challenge due to the difficult industrial transfer.
Pharmacokinetic and Toxicological Studies of Nanoparticles as a Delivery System Pharmacokinetics, often described as what an organism does to a drug, is a branch of pharmacology dealing with the study of the activity of compounds in the body over a period of time with a primary focus on processes by which medicinal products and drugs are absorbed, distributed, metabolized, and finally excreted ADME. Figure 6. Toxicity of Drug Delivery Systems Toxicity remains a challenge even when applying nanoparticles as drug carriers.
The Problems of Nanotechnology in Practical Use. The Limitations and Concerns of Different Types of Nanoparticles for Drug Delivery Applications In view of this paper, the use of nanotechnology in practice may face some challenges. Challenges in Pharmacoeconomic Aspects of Nanocarriers as Drug Delivery Systems Nanomedicine adopts the use of nanotechnology for highly specific medical interventions for the prevention, diagnosis and treatment of diseases, all of which are presented in this paper.
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To assist decision-makers in identifying the preferred choice among possible alternatives. To compare medications or interventions with different outcomes.