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Review Article ISSN: 0976-7126 CODEN (USA): IJPLCP Gawai et al., 11(4):6540-6548, 2020

[[ A Review on , their preparation and applications Ashish A. Gawai, Rahul J. Sarode and K.R. Biyani Anuradha College of Pharmacy, Chikhli, Buldana, (M.S) - India

Abstract Article info The aim of pharmaceutical nanotechnology is to deliver the drug in the form of nanoparticles by enhancing their therapeutic potential. Received: 30/01/2020 Nanoparticles are solid colloidal particles ranging size 10 to 1000 nanometer, possess a matrix structure which incorporate Revised: 28/02/2020 pharmacological active substances & facilitate control release of active agent. While the nano capsule contains an oily core incorporating drug Accepted: 13/04/2020 surrounded by membrane structure. Nanoparticals use to successfully deliver the verity of drug protein, peptide & genes to cell both as non- © IJPLS targeted & targeted form. Drug can coupled in monomers that are specific for cell & organs. This strategies use to concentrate drug in www.ijplsjournal.com selected targeted tissues thus minimizing side effect & toxicity.

Nanoparticles are prepared from either synthetic or natural macro molecules using two distinct techniques that is bottom up& top down technology. The bottom up technology adopts method to aggregate molecule into particle of nano range, while top-down adapt to breaking down macro molecules into nano range. Nano-tubes are used to deliver drug into targeted tissue cell & organs meanly use membrane. DNA nanotube, pharmaceutical nanoparticle are those where the drug is dissolved entrapped encapsulated or adsorbed on surface.

Keywords: Nanoparticles, Encapsulated, Nanopolymers

Introduction Nanoparticle is a small object that behaves as a therapeutic efficacy &reduction in side effect can whole unit in terms of its transport & properties, be achieved by various routs of administration size of nanoparticle is 1 to 100 nanometer, including oral, nasal, injection and intraocular use. nanocluster have at least one dimension between 1 Copper nanoparticles smaller than 50 nanometer & 10 nanometer & narrow size distribution, are consider super hard material that do not nanopowder on the other hand are agglomerates exhibit the same malleability & ductility as bulk of ultrafine particles of nanoparticle or copper. Ferroelectric nano particle are smaller nanocluster. Nanoparticle size crystals are called than10 nanometer. Suspension of nanoparticle are nanocrystals.1-4The size and surface characteristics possible because the interaction of particle surface of nano particles can be easily manipulated and with the solvent is strong enough to overcome this could be use for both passive & active differences in density which usually result in targeting. Nanoparticles can be made to control & material either sinking or plotting liquid. sustained release of the drug during the transportation as well as the location of the *Corresponding Author release. Since distribution & clearance of the drug E.mail: [email protected] from the body can be altered & increase in drug

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Gold nanoparticle appears deep red to black in fluid. Platinum nanoparticles can be made with solution size 1 to 10 nanoparticle. They have very size between 2 to 20 nm. high surface area to volume ratio. The coarse suspended in the brownish red or black color in particle are in the range 10000 to 2500 nanometer, colloidal solution.12 then fine partical are in the range 2500 to 100 4) Gold Nanoparticles nanometer &nano particle are in the range 100 to Gold nanoparticles are used in immunochemical 1 nanometer.5-7 studies for identification of protein interaction. They are used as a Lab tracer to detect presence of Classes of Nanoparticle DNA in a sample. Gold is even use in some The nanoparticles can be of Polysaccharide, medicines for targeted system. The powders & granules, protein & , soil & gold nanoparticleis more beneficial as it really sediments, surface &interfaces, suspension small with diameter of 5 nm or less.13 slurries & pastes, viruses & vaccines.8 5) Silver nanoparticles are used to kill bacteria Use of nanoparticle in biology & medicine9 because of good electrical & thermal conductivity. 1) Creating Fluorescent biological labels for It contains large number of silver ions & its important biological markers & molecule in surface use in antimicrobial agent.14-15 research & diagnosis of disease. 2) Gene delivery system in General Method of synthesis of nanoparticle 3) For biological detection of disease causing The process of condensation leads to fine powder organisms & diagnosis with irregular particle sizes and shapes intypical 4) Detection of proteins powder. These may lead to non-uniformity of 5) Isolation & purification of biological structure in the package nanoparticle that may molecules & cell in research lead in packaging density variation in the compact 6) Probing of DNA structure powder. In addition un controlled agglomeration 7) Genetic and tissue engineering of powder due to attractive Vander walls forces 8) Destruction of tumors with drugs may also results in non-homogenous formation 9) In MRI studies nano-clusters & nano particles packages. There 10)In pharmacokinetic study are variations in stresses that can result in non-

Types of Nanoparticles use in Pharmacy uniform drying shrinkage & this is directly 1) Magnetic Nanoparticles proportional to the rate at which the solvent can These are the class of Nanoparticles which can be be removing. Porosity & its distribution these manipulated using magnetic field which determines the process to a large extent, such commonly consist of magnetic elements such as stresses have been associated with a plastic to , nickel, cobalt etc. While magnetic brittle transitionin consolidated bodies & lead to nanoparticles smaller than 1 micrometer in propagation of cracks. Homogeneity may further diameter i.e., (5-500nm) have been focus of much be compromised where there are fluctuations in research because they possess attractive packing density in the compact as it is prepared properties.10 for during the sintering process. Some pores & 2) other structural defects associated with density With diameter between 1 to 100 nm, the two main variations have been shown to play a detrimental forms of iron oxide nanoparticles i.e., magnetic role in the sintering process. Finally produce nano and magnetite have attracted extensive interest material of uniform size & shape most important due to their super paramagnetic properties and the distribution of components and porosity.16 potential application in Pharmaceuticals use in catalysis, sensor, medical diagnosis and Uniformity of Nanoparticles therapeutics.11 In the synthesis of nanoparticle, high purity and 3) Platinum Nanoparticle uniformity of structure is necessary for putting Usually in the form of suspension or collides of this particle to use. There must be high purity sub micrometer size particle of platinum in a ceramic polymers, glass ceramic & material

International Journal of Pharmacy & Life Sciences Volume 11 Issue 4: April. 2020 6541 Review Article ISSN: 0976-7126 CODEN (USA): IJPLCP Gawai et al., 11(4):6540-6548, 2020 composites in creation of this particle. into the aqueous phase containing pluronic Nanoparticle is generally classified based on their f68under magnetic stirring. The colloidal dimensionality, morphology, composition, suspension obtained was concentrated by agglomeration and uniformity.17 evaporation under vacuum & filter to obtain nanocapsule. The nano capsule possess cell like Nanoparticle can improve medical diagnostic structure with a wall thickness of 3nm around Early detection of disease remains a primary goal nanocapsule& pH range is 4 to 10.Similar to of the medical community. Nanoparticle holds prepared (PIHCA) polyisohexylacynoacrylate great promise to achievement of this goal. involving treatment of monomer with sulphur Nanoparticle in particular have exhibited dioxide & dissolved in a solution containing tremendous potential for detecting fragment of miglyol810 in ethanol, this solution was added viruses, pre-cancerous cells, disease markers & slowly in 1:2 ratio into aqueous phase containing indicators of radiation damage. Gold coating has solution of 0.5% poloxamer 407 & 10mm made it possible to use toxic cobalt nanoparticles phosphate buffer under stirring were purified for biomedical application. Gold coated centrifugation & washing with distilled water. ferromagnetic nanoparticle tagged with HIV The presence of non-ionic allowed antibodies may be able to detect virus particles polymerization of ethyl cyanoacrylate at O/W left after completion of conventional drug interface. Thus encapsulating miglyol812 droplets therapy.18 the immediate polymerization triggered formation of drug loaded nanocapsule. The suspension were Nanoparticle can improve targeted drug concentrated under vacuum to remove acetone to delivery method produce smaller size nanocapsule.21,22 system can convey drugs more effectively and more conveniently that Nanotubes23 increases patient’s compliance, extent the product Nanotubes are generally used to deliver drug into life cycle, provide product differentiation & targeted cell, tissue & organs they are reduce health care cost. Targeted drug delivery mainly classified into four types. rely on nanoparticles compounds characterized by 1) Carbon nanotubes:S pinning carbon low oral due to poor water nanotubes are with a , permeability, instability and provide for cylindrical nano structure. Nanotubes have longer sustained & controlled release profile.19 been constructed with length to diameter ratio Characterization of Nanoparticles20 of up to 132,000,000: 1 significantly larger 1) Particle diameter < 100 nm than for any other material. These cylindrical 2) Electrical charged- ₰ potential carbon moleculesare valuable for science & 3) Pharmaceutical stability technology to their extraordinary thermal 4) Physical stability in drug (no aggregation) conductivity & electrical properties. 5) Nontoxic, biodegradable & biocompatible 2) Inorganic Nanotubes: Is a cylindrical metal 6) Scalable & cost effective MFG process composing of metal oxide. They occurred in 7) Amenable to small molecules, peptides, some mineral deposits. protein or nucleic acid 3) Membrane Nanotube: Also called cytaneme 8) Possible modulation of drug release are long & thin formed from the plasma profile membrane that connect different animal cells Nanocapsules over long distance & could sometimes extend Nanocapsule is spherical structure which is form for over 100 micrometer between T cells. by an envelope of polymer film surrounding a Two types of nanotubes have been observed. liquid central cavity. The technique for The first is less than 0.7 micrometer in preparation of (PIBCA)Polymeric diameter contain actin & carry portion of isobutylcyanoacrylate nanocapsule are by plasma membrane between cell in both injecting organic phase consisting of oil with direction and second type is larger than 0.7 dissolved drug, isobutylcyanoacrylate ðanol micrometer contains both actin and

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microtubules can carry components of polymerization. Ionic polymerization may be cytoplasm between cells such as vesicles & anionic or cationic. organelles. This structure may be involving in 2) polymerization: The monomer is cell to cell communication transfer of nucleic emulsified in non-solvent containing acid between cell in a tissue and spread of surfactant which leads to formation of pathogens or toxins. monomer swollen & stabilized droplets. Polymerization required initiator Application of Nanotubes24 which generates radicals/ions defending upon 1) Nanotubes bounds to an that destroy the type of initiator a nucleate, the monomeric breast cancer tumors. The antibodies carrying unit and start polymerization process. The nano tubes are attracted towards proteins particle obtained in emulsion polymerization produces by a one type of breast cancer cell. is small (100-300nm.) Then nanotubes absorbed light from an 3) In an organic continuous phase: In this infrared laser incinerating the nanotubes & the process, the water soluble monomers are tumors. polymerized e.g. acrylamide & cross linker 2) Carbon nanotubes have developed to detect N,N’-bisacrylamide were prototype protein indicative of oral cancer providing monomers to be polymerized using chemical results in less than hour. initiator such as N, N, N’ N’–tetra methyl 3) Medical implants made of porous plastic ethylene diamine and coated with Carbon nanotubes, therapeutic potassiumperoxidesulphate or light irradiation drug are attached to nanotubes can be release and ultraviolet (U.V) radiations. High toxicity into blood stream this developing in plant of monomer required high amount of organic called biocapsule. solvent & surfactant for this technique. Polyalkyalcyanoacrylate (PACA) is prepared Types of preparation of nanoparticle : by this method. Nanocapsulesare also formed 1) Polymeric nanoparticle during polymerization by this method. 2) Solid nanoparticle a) In an aq. continuous phase: This 3) Hydro gel nanoparticle technique required wide variety of 4) Peptide nanoparticle monomer includes alkylcyanoacrylates. It 5) Nanocrystals &nanosuspension requires low amount of surfactant & stabilized newly form polymer particle. In Preparation of polymeric nanoparticle aq. media containing A) By Polymerization process25,26 dextran,hydroxylpropyl, 1) Dispersion polymerization: The Monomer polyethylcyanoacrylate has solvent hence newly form polymer has andpolyisobutylcyanoacrylates (PIBCA) insoluble, polymer forms in continuous phase nanosphere containing metaclopramide & precipitation as particles. The nucleation of have been prepared by this technique. The aq. monomer solution when this chain technique result in only 9.2 to 14.8 % exceeds a critical chain length, small particle drug loading, respectively due to lose of is formed by aggregation of growing polymer water soluble drug in aq. Polymerization chain & precipitation form continuous phase. media. The cyanoacrylate monomer is Stable colloidal particles are formed by initiated by OH- ions & the coalescence & with aggregates. In this polymerization was performed by low pH technique the monomer is dispersed or to control reaction, rapid polymerization dissolved in aq. medium form polymer resulting in precipitation of large polymer precipitation out. Initiation of monomer of aggregates. The stabilizer influence on polymerization which may generate ion or size of formed polymer particle. High radicals to start polymerization process. concentration of poloxamer reduce Nucleation of polymer is called ionic particle size of PIBCA Nanoparticle from

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around 200nm without emulsifier down to nanoparticle is supercritical fluid technology about 31-56nm. (SCF). SCF technology facilitates rapid precipitation and form of dry nanoparticle. B) Nanoparticle Prepared from performed They can use environment friendly solvent polymer such as CO2, nitrogen, particle form with high 1) A. Solvent evaporation method27: In this purity and low traces of organic solvent. SCF method, the polymer solution is prepared in techniques mainly divided into two major organic solvent such as chloroform, ethyl types. acetate or dichloromethane. The drug to be a) Rapid expansion of supercritical encapsulated is dissolved in polymer solution. solution for drug soluble in SCF The organic phase emulsified with aq. Phase (RESS). containing surfactant to abstained oil/water b) Supercritical anti-solvent process for emulsion, the organic solvent is then drug insoluble in fluid (SAS). evaporated at elevated temp or reduced In RESS the solute is solubilized in SCF and pressure. The size of resulting nanoparticle solution is expanded through a nozzle causing greatly depends on size of emulsion droplets sudden decrease in solubility followed by formed prior to solvent evaporation. The size particle pptn. The solvent power of SCF can be controlled by number of factor such as eventually decrease result in precipitation of stirring rate, type and amount of dispersant, solute, in this technique each particle is viscosity of organic and aq. phases and temp. surrounded by same kind of particle in etc. The surfactant use in emulsion formation expansion zone & often result in larger includespoloxamers, polysorbates 80polyvinyl particle due to aggregation(29). In SAS the alcohol.Higher PVA concentration in PLGA solute is dissolved in organic solvent and nanoparticles leads to decrease in nanoparticle solution is charged into SCF in precipitation size. vessel, at high pressure anti -solvent enter into B. Emulsification solvent diffusion liquid phase & result solvent power will be method28 lower & solute precipitate out after The technique employs use of water miscible precipitation, when final operation pressure is solvents such as acetone or methanol along reached, the anti-solvent flows through the with nonpolar solvent which were used as vessel so as to strip the residual solvent. The organic phase. Due to solubility of polar solvent content reduced to desired level the organic solvent in water they spontaneously vessel is depressurized & solid product is diffuse into aq. phase and interfacial collected. turbulence is created between two phases leading to precipitation of droplets as small as Evaluation of polymeric nanoparticle31-33 polymeric nanoparticle. As organic solvent Particle size: The methods of size analysis are utilized hazardous to environment various photon correlation spectroscopy (PCS) and laser other technique such as diffractometry. PCS determines hydrodynamic a) Salting out technique diameter of the nanoparticle via Brownian motion, b) Emulsion diffusion technique. the electron microscopy determine exact particle 2) Super critical fluid technology30 size but required coating of conductive material Hydrophobic drug have problem of low such as gold. The gold coating usually results as solubility, poor bioavailability and irregular size more than normal & also procedure is limited absorption after oral administration. to dry sample. Another one is transmission Nanoparticle can be prepared by size electron microscopy (TEM), with or without distribution, wet melting & high pressure staining is a relatively easier method of particle homogenization. But contamination of size determination, not been stained, not electron product at degradation due to high temp. dense or melted when irradiated by electron beam Generated during processing. The most of microscope cannot be visualized by this popular method for preparation of method. Such nanoparticles are visualized by

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TEM after freeze substitution. Investigation of transportation. Nanoparticles are most logical nanoparticle surfaces recently new types of high approach for transportation,success of resolution microscopes such as atomic force transportation depends upon smaller size (< microscope, lesser force microscope and scanning 100 nm) prolong circulationtransport by & tunneling microscope are developed. transcytosis. E.g. polysorbate 80 coated Molecular weight: Dissolution of particles in PBCA Nano particle where shown to appropriate solvent and its analysis results successfully delivery associated with obtained only if polymer standards have similar hesapeptidedalarginto the brain as determine structure & similar properties as test material. by its therapeutic effect. Coating modified Density:Perform by helium compression tissue distribution & decrease the distribution pycnometry& by density gradient centrifugation. of nano particle to organs of reticulo Structure & Crystallinity: Can be determined by endothelial system significantly coated x-ray diffraction thermo analytical method. nanoparticles are higher concentration around Hydrophobicity: Two major methods such as brain. Increase retention & absorption of contact angle measurement & hydrophobic nanoparticle in brain capillary. Opening of interaction chromatography can be performed tight junction to allow penetration of drug. onlya flat surface where in differentiation between Inhibition of p-glycoprotein associated with nanoparticle with different surface property can be efflux process. obtained by loading particles & columns with alkyl sepharose& eluting then with a triton x-100 c) Delivery of nano particle to cancer cell36-37: gradient. some drugs gets poorly incorporated into cancer cell by substrate to p-gp& multidrug Application of polymeric nanoparticles in drug resistance associated protein (MRP) efflux delivery pumps e.g. doxorubicin. To overcome this a) Opthalmic delivery of nanoparticles34:Oral problem such drug are incorporated into &i.v.administration of drug for treatment of nanoparticles.Doxorubicin conjugated with ocular diseases is very little due to poor PLGA nanoparticle show greater antitumor concentration attained in retina. Delivery of activity after single dose injection in drug to macula was partly successful by subcutaneously. PEGylated gelatin injection through various routs such as nanoparticle show enhances blood circulation subconjunctival, juxtascleral or direct time & uptake into lewis lunges carcinoma intraquitreal injection. However this mode of grown as solid tumor. Smaller size chitosan therapy apart from rapid onset of action, also nanoparticle (64nm) found to possess results in rapid clearance of drug & demands antitumor activity when tested in MGC803 multiple doses at frequent intervals which is human gastric carcinoma cells. The PIHCA not always advisable. Polymeric system such nanoparticles improved antitumor activity of as nanoparticle solves this problem due to Doxorubicin in vivo in hepatocellular their ease of administration &injectability. carcinoma bearing transgenic mice over E.g. budenoside was successfully delivered expressing mdr-1 & mdr-3 gene. through nanoparticles into subconjunctival space to suppress vascular endothelial growth d) Delivery of nanoparticle to factor expression. Second e.g. is intravitreal macrophages38:The Nanoparticles are administration of dye (Rh-6G [Rh])or nile red extensively taken up by through (NR) loaded PLA nanoparticles result in their macrophages phagocytic receptors such as immediate appearance in vitreal space. mannose receptors, D-galactose receptors&scanvenger receptors. mannose b) Brain delivery of polymeric receptors bound nanoparticle are injested by nanoparticle35:Blood brain barrier (BBB) is a the macrophages at a faster rate. Surface tight endothelial junction prevent transport of charge & chemistry of nanoparticles also molecule into brain requiring of carrier for

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Cite this article as: Gawai A.A., Sarode R.J. and Biyani K.R. (2020). A Review on nanoparticles, their preparation and applications, Int. J. of Pharm. & Life Sci., 11(4): 6540-6548. Source of Support: Nil Conflict of Interest: Not declared For reprints contact: [email protected]

International Journal of Pharmacy & Life Sciences Volume 11 Issue 4: April. 2020 6548