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Premium member Presentation Transcript NANOPARTICULATE DRUG DELIVERY SYSTEM : A REVIEW: NANOPARTICULATE DRUG DELIVERY SYSTEM : A REVIEW 1 By Mr. Satish D. Pawar Email:- email@example.comCONTENTS...: CONTENTS... 2 Introduction Properties of nanoparticles Advantages of nanoparitcles Preparation of nanoparticles Pharmaceutical aspects Characterization Polymers used Types of nanoparticles Novel nanoparticle system Applications Toxicity of nanoparticles Marketed products Conclusion ReferencesPowerPoint Presentation: 3 Introduction: Nanoparticles are sub-nano sized colloidal structures composed of synthetic or semi synthetic polymers. Nanoparticles are defined as particulate dispersions or solid particles with a size in the range of 10-1000 nm. The drug is dissolved, entrapped, encapsulated or attached to a Nanoparticles matrix. Depending upon the method of preparation, Nanoparticles, Nanosuspension or Nanocapsules can be obtained.PowerPoint Presentation: 4 Properties of nanoparticles: Surface properties of nanoparticles: Surface hydrophobicity. Zeta Potential. Particle size & Particle distribution: Determine the in vivo distribution, biological fate, toxicity & targeting ability. Drug loading: should have a high drug-loading capacity. Drug release: Solubility of drug. Desorption of the adsorbed drug. Drug diffusion through the nanoparticle matrix. Nanoparticle matrix degradation.PowerPoint Presentation: 5 Advantages of nanoparitcles : Passive & active drug targeting in parenteral administration. Control & sustain release of the drug. Site-specific targeting. Used for various routes of administration including oral , Nasal, Parenteral, intra-ocular etc. High drug loading.PowerPoint Presentation: 6 Preparation of nanoparticles: 1.Polymerization method: A) Emulsion polymerization. e.g. Polyacrylamide nanospheres B) Interfacial polymerization. e.g. Poly( alkylcyanoacrylate ) nanoparticles C) Interfacial polycondensation. e.g. phtaloyldichloride monomer( lipophilic) diethylenetriamine monomer(hydrophilic) 2. Nanoparticles obtained from preformed polymers: A) From Synthetic preformed polymers. B) From natural macromolecules.PowerPoint Presentation: 7 Nanoparticles obtained from preformed polymers: A)From Synthetic preformed polymers. I ) Emulsification/solvent evaporation. Only applied to liposoluble drugs . e.g. albumin, tetanus toxoid, testosteronePowerPoint Presentation: 8 II ) Solvent displacement and interfacial deposition: Lipophilic drugs. e.g. Parenteral bifonazole and clotrimazolePowerPoint Presentation: 9 iii)Emulsification/solvent diffusion: e.g. mesotetra porphyrin-loaded nanoparticles, plasmid DNA-loaded PLA nanoparticlesPowerPoint Presentation: 10 iv) Salting out with synthetic polymers: Salting-out agents, such as magnesium chloride, calcium chloride etc. e.g. poly-(methacrylic) acid nanospheresPowerPoint Presentation: 11 B) Production from natural macromolecules: i ) Albumin nanoparticles produced in an external-oily emulsion: Homogenization of oil phase containing the albumin droplets and thermally stabilized by heating at 175 0 to 180 0 C for 10 minutes. ii) Gelatin nanoparticles produced in an external-oily emulsion: Gelation by cooling emulsion below the gelation point. filtered, washed, and cross-linked with formaldehyde. iii)Alginate nanoparticles: Gelation by addition of a low concentration of calcium. Clusters of calcium alginate gels .PowerPoint Presentation: 12 iv) Chitosan nanoparticles: Complex formation between chitosan and polyanions or the gelation of a chitosan solution dispersed in an oil emulsion . v) Agarose nanoparticles: For administration of therapeutic proteins and peptides Gelation by diluting the emulsion with cold corn oil under agitation at 5 0 CPowerPoint Presentation: 13 Pharmaceutical aspects : Sterilization of nano particles Aseptic technique Autoclaving or γ -radiation Freeze drying of Nanoparticles Prevention from degradation of polymer Prevention from drug leakage, drug desorption and drug degradation. Easy to handle and store. Purification of Nanoparticles Gel filtration Dialysis Ultra-centrifugation Cross-flow filtration methodPowerPoint Presentation: 14 Parameters Characterization methods Particle size and size distribution Charge determination Surface hydrophobicity Carrier drug interaction NP dispersion stability Release profile Drug stability Photon correlation spectroscopy (PCS) Laser defractometry (LD) Transmission electron microscopy (TEM) Scanning electron microscopy (SEM) Atomic force microscopy (AFM) Mercury porositometry (MP) Laser Doppler anemometry (LDA) Zeta potentiometer Water contact angle measurement Rose Bengal (dye) binding Hydrophobic interaction chromatography X-ray photoelectron spectroscopy Differential scanning colourimetry (DSC) Critical Flocculation temperature (CFT) In vitro release characteristic under physiological and sink conditions Bioassy of drug extracted from NPs Chemical analysis of drug Characterization of nanoparticles:PowerPoint Presentation: 15 Polymers used: Natural hydrophilic polymers: Proteins Polysaccharides Gelatin Albumin Lectins Legumin Vicilin Alginate Dextran Chitosan Agarose Pullulan Pre-polymerized Polymerized in process Poly(€- caprolactone) Poly(lactic acid) Poly( lactide -co- glycolide ) Polystyrene Poly( isobutylcyanoacrylates ) Poly( butylcyanoacrylates ) Polyhexylcyanoacrylates Poly methyl( methacrylate ) Synthetic hydrophobic polymers:PowerPoint Presentation: 16 Fullerenes: Buckyballs and Carbon tubes Liposomes Nanoshells Dendrimers Quantum dots Superparamagnetic nanoparticles Nanorods Types of nanoparticles :PowerPoint Presentation: 17 Novel nanoparticle system : Solid Lipid Nanoparticles. Copolymerised peptide nanoparticles. Hydrogel Nanoparticles. Nanocrystals and Nanosuspension. Amphilic Block copolymers .PowerPoint Presentation: 18 Preparation of Solid lipid nanoparticles: A) H ot homogenization technique:PowerPoint Presentation: 19 B ) Cold homogenisation technique:PowerPoint Presentation: 20 Preparation Hydrogel nanoparticles:PowerPoint Presentation: 21 Nanocrystals and Nanosuspensions: Dispersion with agitation Milling for few hrs/days High pressure homogenization 1500 bar pessurePowerPoint Presentation: 22 Applications of nanoparticles :PowerPoint Presentation: 23PowerPoint Presentation: 24 It is part of Particulate matter. Trying to achieve a personalized medicine. Carbon in elemental form cause systemic effect. In high-tech industries humans exposed to intentionally generated engineered nanoparticles. Smaller the particles size more surface area nanoparticles very reactive in cellular environment therefore any intrinsic toxicity of the particle surface will be enhanced. Toxicity of nanoparticles:PowerPoint Presentation: 25 Marketed products: Product/group Company Applications Daunoxome ® Gilead Science, Cambridge, U.K. Cancer Doxil ® Johnson & Johnson, Bridgewater, NJ Cancer Myocet ® Sepherion Therapeutics, Princeton, NZ Cancer Amphotec ® Amphotec , Beverly, MA Antifungal Gendicine ® China approved this for Chinese market Gene delivery Accell Powderject Vaccine, Inc. Madison, WI Gene gun Helios Bio Rad Labs, Hercules, CA Gene gun Rexin -G™ Epeius Biotech Corp, Glendale, CA Gene delivery Vitravene ™ ISIS Pharm, Carlsbad, CA AIDS related Medusa® Flamel Technologies, Lyon, France Generic amphiphilic Polymer technologyPowerPoint Presentation: 26 Product/group Company Applications Transdrug ® Bioalliance , Paris, France Cancer Caelyx ® Johnson & Johnson, Bridgewater, NJ Cancer Nanoedge ® Baxter Health Corp, Deerfield, IL Generic delivery Emend® Elan /Merck & Co, King of Prussia, PA Antinausea drug Rapamune Elan /Wyeth, King of Prussia, PA Immunosuppressant Nanocrystal Elan , Dublin, Ireland Generic technology Abraxane ®/ American Bioscience,Santa Monica, CA Cancer Nanoxel Dabur Pharma, India Bioimaging /diagnosticsPowerPoint Presentation: 27 The nanoparticulate systems have great potentials, being able to convert poorly soluble, poorly absorbed & labile biologically active substance into promising deliverable drugs. The core of this system can enclose a variety of drugs, enzymes, genes and is characterized by a long circulation time due to the hydrophilic shell which prevents recognition by the reticular-endothelial system. To optimize this drug delivery system, greater understanding of the different mechanisms of biological interactions, and particle engineering, is still required. Further advances are needed in order to turn the concept of NP technology into a realistic practical application as the next generation of drug delivery system. Conclusion:PowerPoint Presentation: 28 References: 1) Vyas SP, Khar RK,“Targeted and Controlled Drug Delivery: Novel Carrier Systems”,CBS Publishers and Distributors,1 st edition,13-17,331-381. 2) Mohanraj VJ, Chen Y, NPs – A Review, Tropical Journal of Pharmaceutical Research, June 2006; 5 (1): 561-573 3) Marie G, Vargas A, Gurny R and Delie F , NPs for drug delivery: The need for precision in reporting particle size parameters, Eur J Pharm Biopharm,2008,69 4) Reis CP, Neufeld RJ, Ribeiro AJ, Veiga F, Nanoencapsulation I. Methods for preparation of drug loaded polymeric NPs, Nanomedicine : Nanotechnology, Biology, and Medicine 2 (2006) 8– 21 5) Couvreur P, Dubernet C, Puisieux F. Controlled drug delivery with NPs: current possibilities and future trends. Eur J Pharm Biopharm 1995;41:2 - 13. 6) Couvreur P, Barrat G, Fattal E, Legrand P, Vauthier C. Nanocapsule technology. Crit Rev Ther Drug Carrier Syst 2002;19:99-134. 7) Bouchemal K, Briancon S, Perrier E, Fessi H, Bonnet I, Zydowicz N. Synthesis and characterization of polyurethane and poly(ether urethane) nanocapsules using a new technique of interfacial polycondensation combined to spontaneous emulsification. Int J Pharm 2004;269:89- 100. 8) Tice TR, Gilley RM. Preparation of injectable controlled-release microcapsules by solvent-evaporation process. J Control Release 1985; 2:343 - 52. 9) Barichello JM, Morishita M, Takayama K, Nagai T. Encapsulation of hydrophilic and lipophilic drugs in PLGA NPs by the nanoprecipitation method. Drug Dev Ind Pharm 1999; 25:471- 6.PowerPoint Presentation: 29 10) Galindo-Rodriguez S, Alle´mann E, Fessi H, Doelker E. Physicochemical parameters associated with NP formation in the salting-out, emulsification- diffusion, and nanoprecipitation methods. Pharm Res 2004; 21:1428- 39. 11) Quintanar -Guerrero D, Alle´mann E, Fessi H, Doelker E. Preparation techniques and mechanism of formation of biodegradable NPs from preformed polymers. Drug Dev Ind Pharm 1998;24: 1113-28. 12) Patil GV. Biopolymer albumin for diagnosis and in drug delivery. Drug Dev Res 2003; 58:219- 47. 13) Yoshioka T, Hashida M, Muranishi S, Sezaki H. Specific delivery of mitomycin C to the liver, spleen, and lung: nano- and microspherical carriers of gelatin. Int J Pharm 1981; 8:131 - 41. 14) Aslani P, Kennedy RA. Studies on diffusion in alginate gels. I. Effect of cross- linking with calcium or zinc ions on diffusion of acetaminophen. J Control Release 1996; 42:75- 82. 15) Wang N, Wu XS, Mesiha M. A new method for preparation of protein-loaded agarose NPs. Pharm Res 1995; 12:S257. 16) Ibrahim H, Bindschaedler C, Doelker E, Buri P, Gurny R. Aqueous nanodispersions prepared by a salting-out process. Int J Pharm 1992;87:239- 46. 17) Okuyama K, Lenggoro IW, Preparation of NPs via spray route, Chemical Engineering Science 58 (2003) 537 – 547 18) Kang YC & Park SB (1995). A high-volume spray aerosol generator producing small droplets for low pressure applications. Journal of Aerosol Science, 26, 1131–1138.PowerPoint Presentation: 30 You do not have the permission to view this presentation. In order to view it, please contact the author of the presentation.