Nanotechnology is one of the flourishing branches of science which produces and utilities particles of nano–size which can be measured in nanometre. Technique of nanotechnology can characterize, manipulate and organise matter in arranged form, at the nanometre scale which has uprised the level of science, engineering. technology, drug delivery and therapeutics [1]. Particles having diameter in range between 10-100nm are known as Nanoparticles. They are used as targeted delivery system for delivery small and large molecule by changing their pharmacodynamics and pharmacokinetic properties [2]. Size reduction may help in improving the bioavailability, reducing toxicity, solubility and good formulation properties of a drug [3]. Recent developments are addressing the size range below these dimension and because a typical structure size is in the nanometre range, the method and techniques are defined as nanotechnology [4]. With these nanotechnology pharmaceutical the drug can attack directly to the pin point(specific) location. The focus on the specific area will reduce the possibilities of side effect and will result in more effective drug [5]. Target- specific drug therapy and method for early diagnosis of pathologies are the priority research area in which nanotechnology would play a vital part [6].             

Types of Nanoparticles

• Liposomes: The first type of nanoparticle that was applied in drug delivery was lipid vesicles known as liposomes, which was first described in 1976[7]. Liposomes are spherical vesicles composed of amphiphilic phospholipids and cholesterol, which self- associated into bilayers to encapsulate an aqueous in interior. The amphiphilic phospholipids molecules form a closed bilayers sphere to cover their hydrophobic group from the watery environment, while still continuous contact with the watery phase via the hydrophilic head group [8]

• Dendrimers: Dendrimers are spherical in shape, highly branched and dendritic consisting of an initiator core and complex layers with active terminal groups. These layers are comprised of repeating unit each layer is called a generation. The core of a Dendrimers is denoted as generation zero. 

The specific molecular structure of Dendrimers enables them to carry various drugs using their multivalent surface through covalent conjugation or electrostatic adsorption [9]

• Carbon nanotubes: Carbon nanotubes are cylinders of carbon formed of benzene rings that have been applied in biology as sensors to identify DNA and protein, as medical gadgets for the differentiation of different proteins from serum samples and as carriers to deliver drug, vaccine, or protein [10]

• Polymeric nanoparticle: Polymeric nanoparticle are being developed as effective delivery as effective delivery vehicles due to their passive tumour-targeting properties, which lead to the ability to enhance the efficacy and reduce the side effects of chemotherapeutic drug [11]

• Polymeric micelles: A polymer micelle is a nanoparticle structured by one hydrophilic shell and one hydrophobic core. Hydrophobically assembled micelles and polyion complex micelles are the two main classification of polymeric michelle. The former ones usually consist of amphiphilic copolymer with a hydrophobic block and a hydrophilic block [12]

Toxicity of Nanoparticle

Toxicity of Metallic Nanoparticle: Muldoon and colleagues investigated the toxicity of superparamagnetic iron oxide nanoparticle used as MRI contrast agents in rats. The nanoparticle was administered to the brain by either intra- intellectual vaccination or intraarterially. Although the MRI signal intenseness dropped over time (weeks to months), no pathological changes were notice in brain tissue in ordinary rats. These observing are compatible with a toxicity study of iron oxide nanoparticles in mice and dogs performed nearly two decades ago by Weissler and teammate. In this work, the nanoparticle was delivered inside the veins and no acute or subacute toxicity result were found in the analysis of selected tissues or in blood tests. The safety of various iron oxide–based nanoparticles used as contrast agents in clinical use is well-established [13].

Toxicity of Polymeric and Liposomal Nanoparticles

Nanoparticles in all likelihood is the least problematic category regarding toxicity because the particles are generally either made from or covered with natural or highly biocompatible polymer(such as PEG).In drug delivery application, these particles often carry drug that are cytotoxic by design(to kill cancer cells)but they are prevented from attacking other regions of the body by the prevented from attacking other region of the body by the selective targeting described earlier in this review.

Mergering of natural polymers such as chitosan or natural lipids in the group of polymer or liposome-based nanoparticles is useful because these polymers are not identified as invader by the body and are readily metabolized [14].

Nanotechnology in Drug Delivery

The final goal of application of nano-drug delivery systems is to develop clinically beneficial formulations for treating ailmelt in patients. Clinically beneficial drug delivery systems need to deliver a certain amount of a drug that can be therapeutically effective and often over an extended period of time. These type of requirements can be met by the micro scale drug delivery systems produced by nanotechnology. In moreover, inadequate attention has been paid to the fact that the systems have to be introduced into the human body, which consent from the Food and Drug Administration (FDA). The current methods of preparing nano/micro particles are mainly based on double emulsion methods or solvent exchange technique.

Nano-design of drugs by numerous methodlogy like milling, high pressure homogenization, controlled precipitation etc., are explored to construct, drug nanocrystals, nanoparticles, nanoprecipitates, nanosuspensions (for better understanding generally called as nanocrystals).

Controlled drug-delivery strategies have made a considerable effect on medication. In general, controlled-release polymer systems deliver drugs in the ideal dosage for long periods, thus increasing the efficacy of the drug, maximizing patient compliance and enhancing the ability to use highly toxic, poorly soluble or relatively unstable drugs. Nanoscale materials can be used as drug delivery vehicles to develop highly selective and effective therapeutic and diagnostic modalities [15].

Recent Advancement in Nano-Technology

Drug Nano-Crystals: Drug nano-crystals are pure solid drug particles with a mean diameter below 1000nm. A nano-suspension consists of drug nano-crystals, stabilizing agents such as surfactants and/or polymeric stabilizers and a liquid dispersion medium. The dispersion media can be water, aqueous solutions, or non-aqueous media. The term Drug nano-crystals, implies a crystalline state of the discrete particles, but depending on the production method they can also be partially or completely amorphous. Drug polymeric nano particles, which consist of a polymeric matrix and an incorporated drug. Drug nano-crystals do not consist of any matrix material [16].

Gold and Silver Nanoparticles

Silver nanoparticles synthesized through the reduction of AgNO3 using NaBH4. The borohydride anions adsorbed onto silver nanoparticles. The repelling forces of the borohydride anions prevented the aggregation of particle, but the addition of an electrolyte or agitation induced aggregation. The silver nanoparticle sol that, using a spectrophotometer, had Plasmon resonance at 386nm gave off a yellow hue. The silver nanoparticles estimated to be 10 to 20nm in diameter. Gold nanoparticles synthesized through the reduction of HAuCl4 using Na3C6H5O7. The gold nanoparticle sol gave off a red hue had Plasmon resonance at 515nm. The gold nanoparticles estimated to be 10 to 25nm in diameter [17].

Nano-Gel

Gelatin is obtained from the breakdown and hydrolysis of collagen, obtained from the connective tissues, bone and skins of animals. It is a known matrixing agent drug delivery to describes a process for the controlled release of sulphamethoxazole used 2 different gelatin nano-particle {Type A (porcine skin) and type B gelatin (bovine skin)} and cross linked with gluteraldehyde; Nano- particle of varying gelatin concentrations were prepared by solvent evaporation techniques and drug release kinetics evaluated using appropriate kinetic models. Findings from this system suggest that this system could be of use in targeted drug delivery such as colon drug delivery where pH is an important consideration. Drug release was found to increase following increased swelling of the nanoparticles [18].

Solid–Lipid Nanoparticle

Recently, a lipid-based solvent-free formulation process has been developed to prepare lipid nanocapsules in the nanometer range. This process takes advantage of the variation of the hydrophilic–lipophillic balance of an ethoxylated hydrophilic surfactant as a function of the temperature, leading to an inversion phase.

Polymeric Micelles as Drug Carriers Systems

Polymeric micelles have attained attention in drug delivery, partly due to their ability to solubilize hydrophobic molecules, their small particle size, good thermodynamic solution stability, extended release of various drugs and prevention of rapid clearance by the reticulo-endothelial system (RES). Critical micelle concentration (CMC), similar to low-molecular-weight surfactants, is the key characterization parameter for polymeric micelles.

Furthermore, various types of drugs can be loaded into the hydrophobic core of polymeric micelles by chemical conjugation or physical entrapolymeric micelles by utilizing various interactions such as hydrophobic interactions, or ionic interactions, or hydrogen bonding. The hydrophobic core serves as a reservoir from which the drug is released at slow pace over a long period of time.

Polymer-Based Nanoparticulate Drug–Delivery System

• Hydrogel-Based Nanoparticulate Drug-Delivery Systems

• Dendrimer-Based Drug-Delivery Systems

• Calcium Carbonate Nanoparticles

• Protamine-Based Nanoparticulate Drug Carriers (Proticles): Protamine is a non-antigenic and virtually nontoxic peptide from the sperm, the compound derived from salmon, the most widely used source and has a molecular mass around 5000 g/mol. Polymer–based nanoparticulate drug–delivery system can be used as a carrier system for transportation of DNA or oligonucleotides and it is being used as the cationic component

• Chitosan-Based Nanoparticulate Drug-Delivery System: Chitosan, a polycationic polymer, consisting of d-glucosamine and N-acetyl-dglucosamine linked by b-(1, 4)-glycosidic bonds, has been widely used for NPDDSs for delivering anticancer drugs, genes and vaccines Chitosan is a natural polymer and biocompatible. Chitosan nanoparticles also have been evaluated for ocular applications

• Silicone Nanopore-Membrane-Based Drug- delivery system

• Albumin and Gelatin Nanospheres

• Polymeric Nanocapsules as Drug Carriers

• Polystyrene Nanospheres [19]

Application of Nanotechnology

Nanotechnology for Water Purification: Nanotechnology holds great promise for improving the efficacy and efficiency of water treatment. Conclusion derived from most scientific reviews of nano materials stated that the resist linked with these substances managed, but because of the shortage of information regarding toxicity, more health and environmental effects, research is needed. As per some research works smaller particles are not compulsorily more toxic, but the potentiality of these tinier particles to disperse and become mobile in both the environment and the human body must be evaluated. 

If nanomaterials are used in the water market for filtration, disinfection and other treatment, product-specific implications should be considered, particularly for products that are designed to stay or otherwise degrade in situ [20]. Nanoparticles as antimicrobial agents, for water disinfection, used for killing of disease-causing bacteria, viruses and protozoa. Nanomaterials as catalysts, used for extraction of pesticides and other organic matter including toxins. Nanomaterials as sorbents, used for the extraction of heavy metals and inorganic contaminants. Nanomaterials as filtering agents, used for removal of contamination by filtration [21].

Cancer Nanotechnology

Cancer nanotechnology is emerging as a new field of interdisciplinary research, cutting across the disciplines of biology, chemistry, engineering and medicine and expected to lead to major advances in cancer detection, diagnosis and treatment. The basic rationale is that metal, semiconductor; polymeric particles have novel optical, electronic, magnetic and structural properties that are often not available from individual molecules or bulk solids.

Latest research has produced functional nanoparticles that are covalently attached to biological molecules like peptides, proteins, nucleic acids, or small-molecule ligands. Medical applications have also appeared, such as the use of super-paramagnetic iron oxide nanoparticles as a contrast agent for lymph node prostate cancer detection and the use of polymeric nanoparticles for targeted gene delivery to tumour vasculatures. New technologies using metal and semiconductor nanoparticles are also under intense development for molecular profiling studies and multiplexed biological assay [22].

Gene Therapy

Gene therapy is used for diagnosis of several genetic disorders such as haemophilia, cystic fibrosis and tumours. Delivery of gene at targeted point is still a arduous task. Genetic material is not stable and get easily dismentaled by biological environment as well as genetic material fail to cross various biological membranes. Viral vectors are being used for delivery of genes prevailingly. But major issue associated with viral vectors is that they may cause immunological response [23]. This problem can be overcome by using non-viral vectors such as liposomes, nanoparticles, nanocarriers, etc. genetic material can be encapsulated inside the carriers. PLA and PLGA nanoparticles can be effectively used for delivery of plasmid DNA. Chitosan, gelatine, poly-1-lysine and silica nanoparticles are used in gene therapy [24].

Pulmonary Drug Delivery

Efficiency of drug can be improved by reducing the size of drug. If drug is converted into nanopharmaceuticals then it can be directly targeted to lungs by mechanically intervention of capillary bed of the lungs. Different types of nano based formulations are utilised for pulmonary drug delivery such as beclomethasone lipid nanocarriers, solid lipid nanoparticles and liposomes, curcumin polymeric nanoparticles, indomethacin nanoparticles, fluticasone dried nanoparticles, amikacin liposomes, tacrolimus nanoparticles, etc [25].

Oral Drug Delivery

Oral drug delivery remains one of the improntant route of drug administration. Because of its numerous advantages, it is oldest as well as commonest route of drug administration. This route has some limitations too, it cannot deliver certain type of drugs like water insoluble drugs, protein and peptides, drugs which gets destroyed by gastric environment. In case of such limitations, nanotechnology can play an important role. Drugs carried in nanoparticles will be protected from gastric environment as well as solubility of such drugs can be increased which in turn increases the bioavailability. Also, protein and peptide delivery through oral route is possible by use of nanotechnology [26].

Parenteral Drug Delivery

Nanosuspsion is observed as one of the best approach in case of parenteral drug delivery. Nanosuspensions increase solubility of aqueous insoluble drugs [27] Nanosuspension can be targeted to particular site as well as sustain release effect can be obtained. Etoposide is an anticancer drug. Bovine serum albumin prepared nanosuspension of etoposide to decrease its toxicity and obtain drug targeting into lungs. [28].

Commercially Available Nanoparticles

Gold Nano-Sphere: The particles are in narrow size distribution and available from 2 to 250 nm. Gold particles are good quality nano-spheres, used in conjugation studies of protein and antibody as well as in the production of diagnostic test [29].

Silver Nano-Spheres

These nanoparticles are in 1 to 100 nm size ranges. Nanoparticles of sliver are referred as AgNPs, widely exploited for use in biological labeling, photography, sensing, optoelectronics, photonics and photovoltaic cells [30].

Silica Nano-Spheres

The silica particles are stable in organic solvents and water and produced by new dying method. These are easy to disperse and separate as they have density of 2.0 g/cm3Silica particles are available as fluorescent particles and easy to functionalize. They are useful for coupling of oligopeptides, proteins, antibodies, oligonucleotides, DNA [31].

Magnetic Plain Dextran Nano-spheres

The biodegradable magnetic nanospheres are used in the magnetic field assisted radionuclide therapy. The superparamagnetic iron oxide cores are coated with hydrophilic polymers, such as dextran, chitosan, starch, polyethylene imine, ficoll and polyvinyl pyrrolidone (PVP). Their different surface properties were demonstrated via significant difference of particles electrophoretic mobility depending on the pH-value [32].

Melamine Nano-Spheres

The melamine nanospheres modified to achieve a high density of carboxy functional groups. These nanospheres with carboxy group terminated surfaces are utilised for different conjugation reactions in biomedical research, microarray technology, biotechnology in development of different assays, etc [33].

Advantage of Nanoparticle

They are suitable for different routes of administration, Carrying capacity of nanoparticles is high, shelf-stability of drug increases, ability to sustain and control drug release patterns, suitable for combination therapy where two or more drug can be co-delivered, both hydrophobic and hydrophilic drug can be incorporated, system increases the bioavailability of drug, imaging studies can be done utilizing them, It’s used for targeted drug delivery of drugs, development of new medicines which are safer [34-36].

Disadvantage of Nanoparticle

The manufacturing costs of nanoparticle are high which result in overall product cost. Nano particles can start body’s defences and allergic reactions in body because the solvents used in the process of preparations are toxic in nature, Extensive use of poly (vinyl alcohol) as stabilizer may have toxicity issues, Nanoparticles are difficult to handle in physical form because particle-particle aggregation occurs due their small size and large surface area [37-39].

Current and Future Developments

Above discussed data shows that: drug-loaded nanoparticles from the nanotechnology-based drug designs are versatile candidates with multifunctional characteristics for potential applications in biomedical and tissue engineering part of the modern world. Therefore, during the past few years, nanoparticles-based therapeutic agents have been exploited for an enhanced and efficient delivery in the current biomedical sector of the modern world. Furthermore, various new types of novel strategies for a focused drug delivery/release and activation with auto control have also been developed at usage scale. till date, there has been a abundance of pre-clinical and biomedical data regarding different nanotechnology-based drugs and formulations for various diseases including cancer therapies, etc. Superlatively, the aim has been and still is to bypass the multidrug resistance issues with an extra advantage of high efficacy and control or switchable release in the interstitial space inside the tumor/cancerous cells. To achieve such high end goals, the following considerations should be taken into account i.e. 

• Targets which are identified earlier on the surface of tumor cells

• Surface functionalization (ligand attachment) of a drug-carried nano-carrier

• Efficient and long running potential in blood circulation without impairing/leaking the drug agents

• High-end internalization potential

• Control drug release from the nano-carrier inside the target boundary

• Safer elimination without posing adverse effects on the healthy cells

In this context, the nanotechnology-based DDS would be an ideal therapeutic design to control many of the limitations/drawbacks of the traditional therapies in practice. In summary, the development of novel, efficient and highly reliable nanotechnology-based therapeutic DDS for multipurpose applications has tremendous potential to tackle many human-related diseases. Moreover, with the aid of modern nanotechnology, the nano-based bio-medicine has made a positive impact on emerging sectors such as cosmetics, drug delivery technologies and healthcare advances, by providing a better quality of patient life in a more secure way leading to a healthy and foresee-able future [40].

With the help of this review, it would be concluded that “future of medicines is pharmaceutical nanotechnology”. In drug delivery system it has enormous potential to deliver therapeutic and pharmacological agents with the use of nanotechnology dissired properties of therapeutic agents can be enhanced. Thus nanotechnology have potential to solve health related problems. In future nanotechnology makes significant contributions in diagnosis, therapy and prevention of disease. This review provides short description of nanotechnology and will be helpful in future development of pharmaceutical nanotechnology.

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