INTRODUCTION:

Nanoparticles in the range of 10-1000 nm are known as particulate dispersions or solid particles. The product is dissolved, encapsulated, or bound to a layer of nanoparticles. Nanoparticles, nanospheres or nanocapsules may be obtained depending on the preparation process. Nanocapsules are structures where the drug is confined to a space enclosed by a special polymer membrane, while nanospheres are matrix systems where the drug is distributed uniformly and evenly. In recent years, biodegradable polymeric nanoparticles, particularly those covered with hydrophilic polymer such as poly (ethylene glycol) (PEG) known as long-circulating particles, have been used as potential drug delivery devices due to their ability to circulate over a prolonged period of time targeting a specific organ, as DNA gene therapy carriers, and their ability to deliver protein^1-4.

The explanation why nanoparticles (NP) are desirable for such purposes is based on their essential and special characteristics, such as their surface-to-mass ratio, which is much larger than that of other particles and materials, enabling catalytic reaction promotion as well as their ability to absorb and hold other compounds.

The main objectives in the design of nanoparticles as a delivery system are to monitor particle size, surface properties and release of active agents which are pharmacological therapeutic agents to achieve the drug's site-specific action at the therapeutically optimal rate and dosage scheme. While liposomes have been used as potential carriers with unique advantages including shielding drugs from degradation, targeting the site of action and minimizing toxicity or side effects, their applications are limited due to inherent problems such as low encapsulation capacity, in the presence of blood components and poor storage stability, rapid leakage of water-soluble medications. Polymeric nanoparticles, on the other hand, provide other specific benefits over liposomes^5-8.

The benefits of the use of nanoparticles as a drug delivery device include the following:

1. Particle size and nanoparticles surface characteristics can be easily manipulated to achieve any passive and lively drug focused on after parenteral administration.

2. During shipment and on the localization website, they control and sustain the launch of the drug, altering the organ delivery of the medication and eventual clearance of the drug in order to enhance the effectiveness of drug therapy and decrease facet results.

3. Controlled launch and particle degradation traits can be without problems modulated by choice of matrix constituents. Drug loading is enormously high, and tablets can be included in the structures except for any chemical reaction; this is an important aspect for retaining the drug activity.

4. Site-specific targeting can be executed by means of attaching concentrated on ligands to the floor of particles or the use of magnetic guidance.

5. The device can be used for more than a few routes of administration such as oral, Parenteral, Intra-ocular, nasal etc.

Nanoparticles have drawbacks despite these advantages. Its small size and large surface area can contribute to particle-particle aggregation, making nanoparticles in liquid and dry forms difficult to handle physically. Therefore, small particle size and large surface area contribute to minimal drug loading and burst release. Until nanoparticles can be used clinically or commercially available, these practical problems need to be overcome. A study details the latest development of drug delivery systems for nanoparticulate, surface modification problems, drug loading methods, and nanoparticles release control and potential applications.

TYPES OF NANOPARTICLES:

Liposomes:

Liposomes are dense bilayered vesicles in which the membranous lipid bilayer composed mainly of natural or synthetic phospholipids fully encloses an aqueous volume. Liposomes are defined by bulk, surface load and a number of bilayers. It has a number of advantages in terms of amphiphilic structure, biocompatibility, and ease of surface modification, making it ideal for biotech drug delivery. Since its formation, liposomes have been widely used in the fields of genetics, biochemistry and medicine. This alters to a large extent the pharmacokinetic profile of the loaded drug, especially in the case of peptides and proteins, and can be easily altered by the surface attachment of polyethene glycol units (PEG) making it stealth liposomes, thus raising its circulation half-life^9-11.

Table 1: Example of drugs used as a Liposomes

Drug	Purpose
Vancomycin	Antibiotic Drug
Doxorubicin	Ovarian Cancer, Breast Cancer
Amphotericin B	Fungal Infections
Cytarabine	Lymphomatous meningitis
Daunorubicin	Kaposi’s sarcoma
Camptothecin	Anticancer Drug

Solid Lipid Nanoparticles (SLN):

In the early 1990s, solid lipid nanoparticles (SLN) were formed as an alternative carrier system for emulsions, liposomes and polymeric nanoparticles as a colloidal carrier system for controlled drug delivery. The main reason for their creation is to combine the advantages of different carrier systems such as liposomes and polymeric nanoparticles. For parenteral, pulmonary and dermal application paths, SLN was developed and investigated. SLN consist of a solid lipid matrix that typically contains the drug with an average diameter of fewer than 1μm.To prevent aggregation and maintain dispersion, various surfactants with an approved GRAS (Generally Recognized as Safe) status are used. SLN was called the use of cationic lipids for the matrix lipid composition as new transfection agents. Use the same cationic lipids as liposomal transfection agents to formulate cationic solid lipid nanoparticles (SLN) for gene transfer^12-17.

Polymeric nanoparticles:

This consists of a biodegradable polymer similar to SLN or nanosuspensions polymeric nanoparticles (PNPs). There are many benefits of using PNPs in drug delivery, the most important being that they usually improve the stability of any volatile pharmaceutical agents and are easily and cheaply produced by a multitude of methods in large quantities. Polymer nanoparticles may also have engineered specificity, enabling them to deliver a higher pharmaceutical agent concentration to the desired location^12-17. Polymeric nanoparticles are a wide class of vesicular (nanocapsule) and matrix (nanospheres) structures.

Table 2: Example of drugs used as a Liposomes

Drug	Purpose
Clotrimazole	Antibiotic Drug
Doxorubicin	A wide spectrum of tumours.
Carboplatin	Ovarian, head, neck, lung cancer
Lamivudine	Anti-HIV drug

Nanocapsules:

Nanocapsules are systems in which the drug is confined to a cavity enclosed by a special polymeric membrane, whereas nanospheres are systems in which the drug is distributed throughout the polymer matrix. The various natural polymers such as gelatin, albumin, and alginate are used in the preparation of nanoparticles; however, they have inherent drawbacks such as low batch reproducibility, vulnerable to degradation, and possible antigenicity. Synthetic polymers used in the preparation of nanoparticles may be in the form of preformed polymers such as polycaprolactone (PCL), polylactic acid (PLA), or in situ polymerizable monomers such as polyalkyl cyanoacrylate. Dissolve, capture, add or encapsulate the candidate drug in or within the polymer shell/matrix. Based on the preparation process, it is possible to control the release characteristic of the integrated drug. For intracellular and site-specific distribution, polymeric nanoparticulate systems are attractive modules. Because of their size and surface modification with a common recognition ligand, nanoparticles can be made to enter a target site. Their surface is easy to modify and function^12-17.

Nanospheres:

Nanospheres are known from its meaning as a matrix framework in which the matrix is spread evenly. These are networks of spheric vesicles.

Dendrimers:

Dendrimers, a special polymer class, are strongly branched macromolecules that can be accurately controlled in size and shape. Dendrimers are made using either convergent or divergent step-growth polymerization from monomers. The well-defined structure, size monodispersity, surface functionality and stability are dendrimer properties that make them desirable candidates for drug carriers. By complexation or encapsulation, drug molecules can be integrated into dendrimers. Dendrimers are being studied as carriers of penicillin and for use in anticancer therapy for both drug and gene delivery^18-22.

Nanotube:

Carbon nanotubes (CNTs) are carbon allotropes with a cylindrical nanostructure, also known as buckytubes. Nanotubes were designed with up to 132,000,000:1 length-to-diameter ratio, which is significantly larger than any other material. These cylindrical carbon molecules have novel properties that make them potentially useful in many applications in nanotechnology, electronics, optics, and other science of materials, as well as potential uses in architectural areas. These may also have applications for body armour construction. We have extraordinary strength and unique electrical properties and are thermal conductors that are effective. Nanotubes are part of the structural fullerene family, including the spherical buckyballs as well. A nanotube's ends can be covered with a buckyball structure hemisphere. Their name derives from their size, as a nanotube's diameter is in the order of a few nanometers (about 1/50,000th of a human hair's width), while they can be up to 18 centimetres long (as of 2010). Nanotubes are known as single-walled nanotubes (SWNTs) and multi-walled nanotubes (MWNTs). Applied quantum chemistry, specifically orbital hybridization, explains chemical bonding in nanotubes. Nanotubes' chemical bonding consists entirely of sp 2 bonds, similar to graphite bonds. Such bonds, which are stronger than the diamond sp3 bonds, give their special strength to nanotubules. In addition, Van der Waals powers simply form nanotubes into "ropes."s

Nanowire:

A nanowire is a nanostructure with a nanometer (10−9 meters) in diameter. Additionally, nanowires can be described as structures whose thickness or diameter is limited to tens of nanometers or less and whose duration is not restricted. Quantum mechanical effects are significant at these scales— which coincided with the word "quantum wires." There are many different types of nanowires, including metallic (e.g., Ni, Pt, Au), semi-conductive (e.g., Si, InP, GaN, etc.) and isolating (e.g., SiO2, TiO2). Molecular nanowires consist of repeated molecular units, either organic (e.g. DNA) or inorganic (e.g. Mo6S9-xIx). In the near future, the nanowires could be used to attach small components to extremely small circuits. Such components could be produced from chemical compounds using nanotechnology.

Nanocrystals:

Nanocrystal is a single crystalline nanomaterial with at least one dimension at 100 nm. Most precisely, any substance with a scale smaller than 1 micrometre, i.e. 1000 nanometers, should be considered a nanoparticle, not a nanocrystal. For example, any particle that exhibits crystallinity regions should be called a dimension-based nanoparticle or nanocluster. These materials are of tremendous technical importance as many of their electrical and thermodynamic properties are highly dependent on size and can, therefore, be managed by careful production processes. Crystalline nanoparticles are also of interest as they often have crystalline single-domain structures that can be analyzed to provide information that can help understand the behaviour of macroscopic samples of similar materials without complicating grain boundaries and other defects. Semiconductor nanocrystals are often referred to as quantum dots in size range of sub-10 nm. At an ExxonMobil oil refinery in Louisiana, crystalline nanoparticles made from zeolite are used as a filter to convert crude oil into diesel fuel, a process cheaper than conventional methods. In a new type of solar panel called SolarPly developed by Nanosolar, a coating of crystalline nanoparticles is used. It is cheaper, more versatile than other solar panels, and reports an output of 12 percent. (Conventionally cheap organic solar panels turn 9% of the sun's energy into electricity.) Crystal tetrapods 40 nanometers long convert photons into electricity but are only 3% efficient. The word Nano Crystal is a registered Elan Pharma International Limited (Ireland) trademark used in relation to Elan's patented milling process and formulations of nanoparticulate drugs²³.

Table 3: Example of drugs used as a Liposomes

Drug	Purpose
Rapamycin	Immunosuppressive
Megestrol	Anti-anorexia
Carboplatin	Ovarian, head, neck, lung cancer
Lamivudine	Anti-HIV drug

Formulation of Nanoparticles:

1. Nano-precipitation:

It is an easy and fast method performed by adding under constant stirring an organic solution containing polymer and lipophilic material to the aqueous solution in a drop-wise way. Particles of the co-polymer are highly flexible, with both hydrophilic and hydrophobic surfaces. Within the water, hydrophobic parts go inside and hydrophilic parts come out and form a globular structure, whereas hydrophilic drugs are bound to the outer surface of the polymer, and hydrophobic drugs penetrate into the hydrophobic core area. Eventually, this surface of particles can be designed to target ligands such as antibodies. The NP size can be regulated by the additive rate of polymer and the stirring speed²⁴.

2. Emulsification based methods²⁴:

The organic phase contains drug and polymer are agitated/ sonicated in the aqueous phase to form emulsified droplets.

a. Emulsification-solvent evaporation:

Polymer dissolved and emulsified in the aqueous phase in a toxic solvent like chloroform. Formation NP occurs under reduced pressure by evaporating the solvent. Adjusting the conditions of solvent evaporation such as temperature and pressure will improve quality but slow down the process.

b. Emulsification solvent diffusion:

Polymer dissolved in partly dissolving solvents such as benzyl alcohol in pre-saturated water. This creates droplets of oil-water emulsion. The scattered droplets dissolved by a significant quantity of water with stabilizers. Diffusion of organic solvents from droplets leads to nanoparticles being condensed and formed.

c. Emulsification Salting out:

The use of organic solvent dissolves absolutely in water. (Ex; acetone) The organic solvent-containing polymer is emulsified at a high salt concentration in an aqueous phase. The concentrated aqueous solution avoids the interaction of acetone with water. Diffusion of emulsion droplets in a significant amount of water results in an unexpected decrease in the continuous process of salt concentration leading to organic solvent extraction and NP precipitation.

3. Layer by layer synthesis:

It creates electrostatic contact with sodium alginate, dextran sulfate, hyaluronic acid, heparin or conbriatin sulfate between oppositely charged polyelectrolytes such as polylysine, chitosan, gelatin-B complex. Often used as a centre to expand the vesicular structure is the solid form of bioactive agents. Using incubation in the polymer solution, a polymer layer is first absorbed into the colloidal base, washed and moved to the oppositely charged polymer solution. Repeat the multi-coating process that can regulate the kinetics of release. This approach is used to treat bioactive substances such as vitamins, peptides, insulin and nucleic acid²⁵.

4. Genetic engineering method (GEM):

It can regulate the structural, functional properties of drug carriers dependent on recombinant protein such as elastomers such as proteins and proteins similar to silk. GEM can regulate molecular weight, hydrophobicity, site and secondary structure of the drug conjugation and improve the efficiency of transfection²⁵.

5. Electrospray Technique:

The configuration of the NP produces consists of a syringe pump with a polymer solution connected to a power supply of high voltage. Collector of metal foil mounted opposite acts as an electrode on the table. The flow rate and the voltage applied depends on the type of solution used in the process. Solvent evaporation can create solid particles. Particles with electrospray can be used to deliver drugs directly to the target site without polymer²⁶.

Mechanism of drug-releasing by nanoparticles:

The drug bullets are attached to the NP and the power to cure the diseases is included. The nanotechnology-based DDS only delivers the drug appropriately to target sites without any changes occurring in the therapeutic particle of the parent. To become therapeutically successful, the drugs required special pH conditions, poorly water-soluble or high concentration of drugs. The key methods used to bind the drug to the polymer are the encapsulation, non-covalent complexation and conjugation to polymer-carriers via a liable linker. The size of the polymer-drug conjugate is of great importance and should be regulated by changing the polymer's molecular weight. The attachment of drug-polymer affects drug solubility, hydrophobicity and permeabilit²⁵. The NP has the capacity to charge the product, and it depends on the density of the matrix. The efficiency of drug loading can be improved by reducing solubility, increasing ionic interactions between drug and matrix, and optimizing drug load absorption. Covalently attached drug and polymer through linkers and responsive to pH or enzyme. The drug attached to NP can be recognized and killed by the immune cells. To overcome this problem, the surface of the particles is decorated with biodegradable, hydrophilic copolymers to allow long-term circulation of particles. The degradability could be the drug-release rate of regulation. Polyglycolic acid (PGA), polylactic acid (PLA) and its copolymers are commonly used for surface decoration. Because of their ability to condense nucleic acid into nano-sized polyplex with protective and biocompatible PEG coating, PEG copolymers are of greater interest. In addition, PEG can resist adsorption of serum protein, prolonging particle systemic circulation, reducing toxicity. Ligands often attached to the NP surface to deliver the drug to the target site with higher specificity. Antibodies, protein, peptides, carbohydrates, lipoproteins, molecules that are charged. Nucleic acid ligands such as DNA, si. RNA, m. RNA is known as aptamers and are a high affinity and target specific²⁷.

Methods used to enter NP into the body are nasal, intravenous, arterial, dermal, transdermal, and inhalation. The Drug-NP conjugate is injected into the circulation system, and the cells/tissues will take it up. By dissolving, dispersing, and finally reaching the target site, the drug is distributed through the blood. Traditional DDS circulates drug into all cells in the body, while DDS based on nanotechnology provides the drug to the target site through its ligand attraction mechanism. Without degradation in the gastrointestinal tract, the drug-NP conjugate should be able to deliver the drug to the target site without reducing drug activity and volume. Second, attacking cells without affecting other cells should be targeted, and side effects should be that²⁸.

1. Passive targeting-Drugs are distributed to the extracellular matrix and spread to the cell. It improves NP's permeability and the effect of cell retention. Vesicles of the tumour are extremely disorganized, and pores are present. To widen the gap between endothelial cells. Such tumour site pores allow NP to reach tumour cells easily than normal cells. Passive targeting does not extend to all tumours and normal cells due to the lack of pores in some tumour cells. Drug diffusion from NP decreases with decreasing reservoir concentration.

2. Effective Targeting-Ligands with interest, antibodies, aptamers bind in the cell surface to the same receptor. By the expression of receptors or epitopes on the cell surface, nanocarriers bind to the target cell via ligand-receptor interaction. Such receptors are expressed strongly on cells of the tumour relative to other cells.

Biorecognition may bind the NP surface decorated by ligands and these ligands to the surface of the targeted cell with the same receptors. Receptor-mediated endocytosis crosses the NPs into the target cells. In this endocytotic vesicle formed by invaginating a portion of the plasma membrane, enclosed with NPs. With this process, thousands of NP's can easily enter the cell. NPs are converted into endosomes within the cell. Instead, endosomes merge to form large endosomes or lysosomes with each other. Lastly, therapeutic drugs can release controllably in response to enzymes or acid pH by degrading the polymeric NP shell²⁹.

Controllable drug release can be managed in different ways in particular sites,

· Polymers are biodegradable and degraded in a controllable manner to release drug to the site,

· Pores within the polymer may be altered in the preparation process. So the diffusion of drugs happens faster or slower.

· The fusion distance and surface area of the NP can change as the size changes. NP scale also plays an important role; smaller size means a larger region of the earth.

· Drug release and drug breakdown are quicker, and by changing the size of NP, this can regulate engineering.

· Through absorption, swelling, oxidation, or decay, the drugs are released through a matrix. The regulation of the release of drugs by osmotic pressure, mechanical pumping, and electrokinetic transport. Constant drug release can be achieved by modifying nano-fluidic system properties³⁰.

Role of Nano-technology in drug delivery:

DDS is defined by the national institute of health in the USA as, “Formulation of a device that enables the introduction of therapeutic substances into the body and improves efficiency and safety by controlling the rate, time and place of release of drug in the body”. Conventional DDSs have many drawbacks, including poor bioavailability, side effects, low drug load capacity, drug level plasma fluctuation, low therapeutic efficacy, and lack of target delivery. Modern DDS circulates drugs non-selectively to the cells in the body, leading to severe effects such as side effects, multiple drug resistance (MDR) and decreased the concentration of drugs at the target location. Of example, the delivery of traditional drugs to tumour cells in cancer treatment can affect normal tissues that cause nephrotoxicity, neurotoxicity, cardiotoxicity. These drawbacks have inspired scientists to do more work on new DDS. Why nanotechnology can solve these limitations can be understood by exploring the drug delivery process using nanoparticles (NP). The drug delivery cycle may mainly be categorized as; medication or therapeutic substance administration; release of the active part of the drug and movement of active ingredients across the biological membrane to the target site for action. Use nanotechnology in DDS involves transmitting and directing medicinal, therapeutic, and diagnostic agents to the cells with the aid of NPs. Without degradation in the gastrointestinal tract and without decreasing drug activity, the drug-NP conjugate should be able to deliver drugs to the target site. Second, attacking cells without causing harm to other cells should be targeted and side effects can.

Nanotechnology uses in Treatments:

Cancer treatment:

The regular tumour cell drug delivery produces side effects in normal tissues such as nephrotoxicity, neurotoxicity, cardiotoxicity, and multiple drug resistance (MDR) decreases the concentration of drugs at the target location, low accumulation. MDR is largely due to the increase in cell membrane efflux pumps such as P-glycoprotein. Paclitaxel equipped NP can move through drugs without MDR disturbance³¹. NP-based drug delivery system is used to solve these issues. The tumour sites are forming new blood vessels to rapidly provide oxygen and nutrients. Such newly formed vesicles are defective and have a leaky vasculature that allows diffusion of NP. The need for energy is growing, and there is glycolysis. Ultimately produced acidic environment and the advantage of pH used for drug release³².

Nano X-ray nano-particle therapy:

1. In standard X-ray radiation therapy capable of producing free radicals by hydrolysing water molecules. In both tumour cells and healthy cells, it can potentially destroy DNA and other molecular structures. Nano X-ray NP has a self-protecting layer for reducing and suspending unnecessary interactions in water. It is injected into patients with cancer and is connected by limited identification only to tumour cells. Nanox-ray NP is more likely to attract X-ray than vapour. Eventually, to destroy only tumours without harming healthy cells, it can damage both double-stranded and single-stranded DNA in tumour cells.

2. The NPS is bound to highly toxic cancer drugs such as doxorubicin and NP surfaces coated with PEG and target ligands to the target site without damaging healthy cells³³.

3. Phototherapy-Au NP has optical properties that allow near-ultraviolet light to be absorbed. The viability of cells is lost due to the cell's increased temperature above 42° C. Upon body irradiation or under a magnetic field, the NP is heated up, which allows tumour cells to irradiate. Angiogenesis inhibition-metal particles can inhibit the phosphorylation of proteins involved in the angiogenesis process by binding the heparin-binding growth factor to the cysteine residues³⁴.

4. Cetuximab, fluorouracils are medications that are bound to liposomes, hydrogels, crystals to treat oral cancers and remove low solubility, permeability and poor bioavailability³⁵.

Heart Diseases:

This is still being investigated. NP is a translation-generated protein that is used to bind damaged artery regions and to split blood clots. NPS is attempted to deliver proteins to the right place in the arteries under the magnetic field³⁵.

In Diabetics:

Developed NP containing matrix insulin. The enzymes are attached to NP as blood glucose levels increase insulin release enzymes and can effectively control blood glucose levels for several days³⁶.

Ophthalmic diseases:

Polymeric NPs, nanogels, liposomes, micelles, dendrimers, chitosan and protein NPs are investigated to treat various ophthalmic back disease applications such as diabetic retinopathy, retinoblastoma, retinitis pigmentosa. The delivery of drugs and genes to the target tissue to treat subsequent segment diseases such as choroid and retina, enhancing diagnosis and retinal prosthesis. To treat glaucoma nano-diamonds found in contact lenses with the drug (timolol maleate)³⁷.

In Tuberculosis (TB):

Treatment of TB allowed the cells to be supplied constantly and regularly with medications. The NP was connected to drugs such as rifampin (RMP), isoniazid (INH)/pyrazinamide (PZA) and coated with PEG to provide TB cells with drugs that are safe. Researchers try to improve bioavailability, reduce dosing frequency and drug administration methods in TB treatment²⁷.

Bone diseases:

NP dependent on calcium phosphate used in drug delivery for bone diseases without bone tissue toxicity. Arthritis, osteoarthritis, osteosarcoma and cancer of the metabolic bone treated with medicines like bisphosphonates. Good bone regeneration of silica and magnetic NP³⁷.

Central nervous system diseases:

NP will cross the blood-brain barrier (BBB) to deliver medication to brain tumours, Alzheimer's disease, inborn metabolic errors such as lysosomal storage, infectious diseases, and ageing, etc. Most therapeutic particles can not move through BBB, blood-cerebrospinal fluid barrier, or other complex barriers to the central nervous system. Only a small class of drugs or molecules can move through BBB with high lipid solubility and low molecular mass. NP has a high affinity and is clearly capable of transporting drugs by BBB. Some transport molecules, such as growth factors, insulin and transition, can improve drug efficiency and kinetics across a variety of tissues^38-42.

Future Aspects:

DDS will improve the treatment of antitumor therapy, gene therapy, radiotherapy, protein delivery, antibiotics, vaccines, vesicles by BBB in the future based on nanotechnology. Researchers will be able to develop drug packing, tracking, transporting, releasing, interaction with barriers, low toxicity and safe conditions before human application process and the fate of NP drugs should be tested using animal models. Pharmaceutical comprehension when administered to responsive organelles such as nucleus as well as being able to improve NPS in the treatment of bone diseases and bone regeneration. Multi-functional NPs could be produced that are capable of detecting malignant cells, delivering different drugs simultaneously, visualizing the position by imaging agents, destroying cancer cells with minimal side effects, and simultaneously monitoring and treatment. This molecule can be improved to cure diseases such as HIV, cancer and the same nanoparticles that can act like robots in operations such as heart disease. The nanoparticles can be paired with a computer programming framework to control homeostasis in humans automatically, such as blood glucose level, ca-level. We can also strengthen these NPs in the future as good protectors in the body against foreign particles.

CONCLUSION:

Nanotechnologies are designed to enhance the pharmacological and therapeutic properties of traditional drugs as drug delivery systems. The highly toxic and low selectivity drug is delivered through the use of nanoparticles to the target site without collecting anywhere. Nanotechnology improves medication bioavailability, efficacy and selectivity, and decreases side effects and toxicity. For drug delivery, reducing plasma fluctuation, and higher solubility also play a vital role. Specific nanoparticles are used to supply drugs such as polymer miscalls, polymeric NPs, polymeric drug conjugates, dendrimers, nanocrystals, and lipid-based nanoparticles such as liposomes, strong lipids. Inorganic NPs such as NPs from metal (gold, silver, iron, platinum, quantity) and NPs from silica (mesoporous, xerogels). Via various conjugations such as encapsulation, non-covalent complexation and conjugation to the polymer carrier through liable linkers, the drugs are bound to the nanoparticle. After the surface of the polymer is protected by co-polymers such as PEG to receive immune cell protection. Ligands are bound to the target side with antibodies, proteins, charged molecules, carbohydrates, aptamers. The drug conjugate NP enters the cell by passive or active targeting, diffusion or endocytosis mediated by the receptor, respectively. Eventually, in response to changes in enzymes or pH, nanoparticles may release drugs in a controllable manner. Some of them are still developing NP-based drug delivery to cure diseases such as tumours, diabetics, heart disease, and core nervous disease. In the future, the drug delivery dependent on nanoparticles can be further improved to cure the most difficult diseases such as AIDS. Nanotechnology can be developed in the future by developing multifunctional nano-particles to treat all kinds of diseases in humans at the same time.

REFERENCES:

1. Langer R. Biomaterials in drug delivery and tissue engineering: one laboratory's experience. Acc Chem Res 2000; 33: 94-101.

2. Bhadra D, Bhadra S, Jain P, Jain NK. Pegnology: a review of PEG-ylated systems. Pharmazie 2002; 57: 5-29.

3. Kommareddy S, Tiwari SB, Amiji MM. Long-circulating polymeric nanovectors for tumour-selective gene delivery. Technol Cancer Res Treat 2005; 4: 615-625.

4. Lee M, Kim SW. Polyethene glycol-conjugated copolymers for plasmid DNA delivery. Pharm Res 2005; 22: 1-10.

5. Vila A, Sanchez A, Tobio M, Calvo P, Alonso MJ. Design of biodegradable particles for protein delivery. J Control Release 2002; 78: 15-24.

6. Mu L, Feng SS. A novel controlled release formulation for the anticancer drug paclitaxel (Taxol(R)): PLGA nanoparticles containing vitamin E TPGS. J Control Release 2003; 86: 33-48.

7. P. Venkatesan, V. Sree Janardhanan, C. Muralidharan, and K. Valliappan. Acta Chim. Slov., 2012; 59: 242–248.

8. Kannappan Valliappan, Sree Janardhanan Vaithiyanathan and Venkatesan Palanivel. Chromatographia, 2013; 76(5): 287-292.

9. Redhead, H. (1997). “Drug loading of biodegradable nanoparticles for site-specific drug delivery”. The University of Nottingham Nottingham.

10. Dange YD, Honmane SM, Patil PA, Gaikwad UT, Jadge DR. Nanotechnology, Nanodevice Drug Delivery System: A Review. Asian J. Pharm. Tech. 2017; 7(2): 63-71.

11. http://www.nanotechnologydevelopment.com/products/introduction-to- nanoparticles.html

12. Jameel Ahmed Mulla, Sarasija Suresh, Imtiyaz Ahmed Khazi. Formulation, Characterization and in vitro Evaluation of Methotrexate Solid Lipid Nanoparticles. Research J. Pharm. and Tech. 2009; 2(4): 685-689.

13. Amol S. Deshmukh. Solid Lipid Nanoparticles. Res. J. Pharm. Dosage Form. and Tech. 6(4):Oct.- Dec.2014; Page 282-285.

14. Baviskar Anagha, Hiremath Shivanand, Akul Manoj, Pawar Poonam. Effect of Lipids and Surfactants on Solid Lipid Nanoparticle Engineering. Research J. Pharm. and Tech. 2011; 4(4):521-526.

15. Trilochan Satapathy, Prasanna Kumar Panda. Solid Lipid Nanoparticles: A Novel Carrier in Drug Delivery System. Research J. Pharma. Dosage Forms and Tech. 2013; 5(2): 56-61.

16. Surbhi Sharma, M.S. Ashawat, N.S. Solanki. Isotretinoin-Loaded Solid-Lipid Nanoparticles: A Sound Strategy for Skin Targeting. Research J. Pharm. and Tech. 5(11):November, 2012; Page 1375-1384.

17. Khopde AJ, Jain, NK. Dendrimer as a potential delivery system for bioactive In Jain NK, editor. Advances in controlled and novel drug delivery. CBS publisher, New Delhi, 2001, 361-80.

18. P. Venkatesan et al. / International Journal of Pharmaceutical and Biomedical Research. 2011; 2(3): 107-117.

19. R. Sathiya Sundar, A. Murugesan, P. Venkatesan, and R. Manavalan, Formulation Development and Evaluation of Carprofen Microspheres. Int.J. Pharm Tech Research. 2010; 2(3):1674-1676.

20. P. Venkatesan, R. Manavalan and K. Valliappan Microencapsulation: A Vital Technique In Novel Drug Delivery System. J. Pharm. Sci. and Res. 2009; 1(4):26-35.

21. Hussain N, Jani PU, Florence AT. Enhanced oral uptake of tomato lectin-conjugated nanoparticles in the rat. Pharm Res 1997; 14: 613-8.

22. A. Arunkumar et al.,: Formulation, Evaluation and Optimization of Sustained Release Bilayer tablets of Niacin and Green Tea extract by employing Box-Behnken design, J. Sci. Res. Phar., 2016; 5(2): 23-28.

23. Fasiuddin Arif Mohammad, Kishore Rapolu, Shanthan Kumar Valugonda, Srinivas Balusu. Optimization of Cuprous Oxide Nanocrystals Deposition on Multiwalled Carbon Nanotubes. Asian J. Research Chem. 2012; 5(1):116-124.

24. Wanigasekara J, Witharana C. Applications of nanotechnology in drug delivery and design-an insight. Current Trends in Biotechnology and Pharmacy. 2016; 10(1):78-91.

25. Zhang Y, Chan HF, Leong KW. Advanced materials and processing for drug delivery: the past and the future. Advanced drug delivery reviews. 2013; 65(1):104-20.

26. Sridhar R, Ramakrishna S. Electrosprayed nanoparticles for drug delivery and pharmaceutical applications. Biomatter. 2013 Jul 19; 3(3):e24281.

27. Gelperina S, Kisich K, Iseman MD, Heifets L. The potential advantages of nanoparticle drug delivery systems in the chemotherapy of tuberculosis. American journal of respiratory and critical care medicine. 2005 Dec 15; 172(12):1487-90.

28. Stevenson CL, Santini Jr JT, Langer R. Reservoir-based drug delivery systems are utilizing microtechnology. Advanced drug delivery reviews. 2012 Nov 1; 64(14):1590-602.

29. Bamrungsap S, Zhao Z, Chen T, Wang L, Li C, Fu T, Tan W. Nanotechnology in therapeutics: a focus on nanoparticles as a drug delivery system. Nanomedicine. 2012 Aug; 7(8):1253-71.

30. Sakamoto JH, van de Ven AL, Godin B, Blanco E, Serda RE, Grattoni A, Ziemys A, Bouamrani A, Hu T, Ranganathan SI, De Rosa E. Enabling individualized therapy through nanotechnology. Pharmacological research. 2010 Aug 1; 62(2):57-89.

31. Jabir NR, Tabrez S, Ashraf GM, Shakil S, Damanhouri GA, Kamal MA. Nanotechnology-based approaches in anticancer research. International journal of nanomedicine. 2012; 7:4391.

32. Bae YH, Park K. Targeted drug delivery to tumours: myths, reality and possibility. Journal of controlled release. 2011 Aug 10;153(3):198.

33. Dong X, Mumper RJ. Nanomedicinal strategies to treat multidrug-resistant tumours: current progress. Nanomedicine. 2010 Jun;5(4):597-615.

34. Shi J, Votruba AR, Farokhzad OC, Langer R. Nanotechnology in drug delivery and tissue engineering: from discovery to applications. Nano Letters. 2010 Aug 20;10(9):3223-30.

35. Calixto G, Bernegossi J, Fonseca-Santos B, Chorilli M. Nanotechnology-based drug delivery systems for treatment of oral cancer: a review. International journal of nanomedicine. 2014; 9:3719.

36. Kompella UB, Amrite AC, Ravi RP, Durazo SA. Nanomedicines for the back of the eye drug delivery, gene delivery, and imaging. Progress in retinal and eye research. 2013; 36:172-98.

37. Savita More, Sarika Lokhande, Vijay Raje. Review on Solid Lipid Nanoparticles for Ophthalmic Delivery. Res. J. Pharma. Dosage Forms and Tech.2019; 11(1):19-34.

38. Bhaskar S, Tian F, Stoeger T, Kreyling W, de la Fuente JM, Grazú V, Borm P, Estrada G, Ntziachristos V, Razansky D. Multifunctional Nanocarriers for diagnostics, drug delivery and targeted treatment across the blood-brain barrier: perspectives on tracking and neuroimaging. Particle and fibre toxicology. 2010;7(1):3.

39. K Srikanth, M Nappinnai, VRM Gupta. Proniosomes: A Novel Drug Carrier System. Research J. Pharm. and Tech.3. 2010; 3(3): 709-711.

40. Subhashis Debnath, R. Suresh Kumar, M. Niranjan Babu. Ionotropic Gelation – A Novel Method to Prepare Chitosan Nanoparticles. Research J. Pharm. and Tech. 2011; 4(4): 492-495.

41. Utpal Jana, Sovan Pal, G.P. Mohanta, P.K. Manna, R. Manavalan. Nanoparticles: A Potential Approach for Drug Delivery. Research J. Pharm. and Tech. 2011; 4(7):1016-1019.

42. Svapnil Sanghavi, Misam Polara, Dipil Patel, Ruchita Shah, Jayvadan Patel, Manish Patel. Nanoparticle Drug Delivery to Brain – A Review. Research J. Pharm. and Tech. 2012; 5(1): 8-13.

Received on 25.12.2019 Modified on 09.02.2020

Research J. Pharm. and Tech. 2020; 13(10):4996-5003.

DOI: 10.5958/0974-360X.2020.00875.6