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Shiva(Nanoparticles)
Shiva(Nanoparticles)
Shiva(Nanoparticles)
Shiva(Nanoparticles)
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Shiva(Nanoparticles)
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Shiva(Nanoparticles)

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  • u have prepared really very nice presentation......plz send it to me on hdeep922@gmail .com
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  • sir, nice presentation
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  • Resp.sir u have prepared really nice presentation...plz send me your presentation on gautam.gurjar@gmail..com
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  • 1. NANOPARTICLES (ULTRAFINE COLLOIDAL CAPSULES) <ul><li>BY….. </li></ul><ul><li>SHIVA KUMAR.Y </li></ul><ul><li>M.PHARMACY(1 ST Y) </li></ul><ul><li>DEPT:PHARMACEUTICS </li></ul><ul><li>KLE UNIVERSITY </li></ul><ul><li>BELGAUM. </li></ul>
  • 2. CONTENTS…. <ul><li>DEFINITION. </li></ul><ul><li>INTRODUCTION. </li></ul><ul><li>NATURAL HYDROPHILIC POLYMERS. </li></ul><ul><li>SYTHETIC HYDROPHOBIC POLYMERS. </li></ul><ul><li>N.P PREPARATION. </li></ul><ul><li>NOVEL NANOPARTICULATE SYSTEM. </li></ul><ul><li>PH’CEUTICAL ASPECTS OF N.P. </li></ul><ul><li>CHARECTERIZATION OF N.P. </li></ul><ul><li>IN VITRO RELEASE. </li></ul><ul><li>THERAPEUTIC APPLICATIONS OF N.P. </li></ul><ul><li>REFERENCES. </li></ul>
  • 3. Definition : <ul><li>Polymeric nanoparticles can be defind as submicronic (size < 1 μ m) colloidal carriers. </li></ul><ul><li>(or) </li></ul><ul><li>Nanoparticles or nanocapsules are vesicular system in which the central valume surrounded by continuous polymeric sheath. </li></ul>
  • 4. Introduction : <ul><li>These n.p are having nanometer size rang 10 -1000 nm. </li></ul><ul><li>These n.p are more stable then liposomes in biological fluids and storage due to their polymeric nature. </li></ul><ul><li>Nanospheres consists of a dense polymeric matrix, in which the drug can be dispersed. </li></ul><ul><li>Nanocapsules having liquid core surrounded by polymeric shell. </li></ul><ul><li>Polymeric n.p cannot be sterilized by autoclaving .They have been sterilized by γ –radiation. </li></ul>
  • 5. Natural hydrophilic polymers Alginate Daxtran Chitosan Agarose Pullulan Gelatin Albumin Lectins Legumin vicilin polysaccharides Proteins
  • 6. Synthetic hydrophobic polymers The polymers used are either pre-polymerized or synthesized before (first group) or during the (second group) process of n.p preparation. Poly (isobutylcyanoacrylates) (PICA) Poly (butylcyanoacrylate) (PBCA) Polyhexylcyanoacrylates Poly (lactic acid) (PLA) Poly (lactide-co-glycolide) (PLGA) polystyrene Polymerized in process Pre-polymerized
  • 7. N.P preparation <ul><li>Cross linking of amphiphilic macromolecules </li></ul><ul><li>The technique of their preparation involves firstly , the aggregation of amphiphile ,followed by further stabilization either by heat denaturation or chemical cross- linking. </li></ul><ul><li>These process may occur in a biphasic o/w or w/o type dispersed system. </li></ul>
  • 8. Cross linking in w/o emulsion
  • 9. Phase separation in aqueous medium (desolvation) <ul><li>The protein or polysaccharide from an aqueous phase can be desolvated by P H changes or change in temp. or by adding some appropriate counter ions. </li></ul><ul><li>The method having three steps </li></ul><ul><li>Protein dissolution. </li></ul><ul><li>Protein aggregation. </li></ul><ul><li>Protein deaggregation. </li></ul><ul><li>The aggregation size should be maintained by appropriate level of desolvation & resolvation. </li></ul><ul><li>Cross –linking agent (glutaraldehyde) , desolvating or deaggregating agent (ethanol , isopropanol , sodium sulphate) are carefully added. </li></ul>
  • 10. <ul><li>Both lipophilic & hydrophilic drugs could be entrapped in N.P using this technique. </li></ul>Aqueous phase (protein aqueous solution ) Protein aggregates (coaservates) Protein colloidal dispersion Nanoparticle dispersion desolvation resolvation Cross-linking
  • 11. P H induced aggregation <ul><li>Rohdewold ,prepared gelatin nanosheres </li></ul><ul><li>Gelatin & tween 20 were dissolved in aqueous phase &the P H of the solution was adjusted to the optimum value. </li></ul><ul><li>the clear solution is heated to 40 0 c </li></ul><ul><li>sequential temp. treatment resulted in to a colloidal dispersion of aggregated gelatin </li></ul>
  • 12. <ul><li>the aggregates were finally cross-linked using cross-linking agent (glutaraldehyde) </li></ul><ul><li>nanoparticles (size is 200 nm) </li></ul><ul><li>The optimal pH range for ideal & uniform preparation of gelatin N.P was 5.5 – 6.5 </li></ul><ul><li>The PH value below 5.5 produced no aggregation while above 6.5 an uncontrollable aggregation. </li></ul>
  • 13. Counter ion induced aggregation <ul><li>The aggregation of dispersed phase (polysaccharides) can effectively be initiated by adding some appropriate counter ions. </li></ul><ul><li>The aggregation can be propagated by adding secondary species. </li></ul><ul><li>Eg: alginate N.P are prepared by using counter – ion induced gelatin technique , where gelatin was induced by ca ++ , and continued by addition of poly (1-lysine). </li></ul>
  • 14. 2. N.P preparation using polymerization based method. <ul><li>Two different approaches are generally adopted for the preparation of nanospheres using in situ polymerization technique. </li></ul><ul><li>methods in which the monomer to be polymerized is emulsified in a non-solvent phase (emulsion polymerization) </li></ul><ul><li>Methods in which the monomer is dissolved in a solvent that is non-solvent for the resulting polymer. </li></ul>
  • 15. Emulsion polymerization <ul><li>Two different mechanisms were proposed for the emulsion polymerization </li></ul><ul><li>Micellar nucleation (micellar polymerization mechanism) </li></ul><ul><li>Homogenous nucleation (homogenous polymerization mechanism) </li></ul>
  • 16. Micellar nucleation:
  • 17. <ul><li>The monomer is emulsified in the non-solvent phase with the help of surfactant. </li></ul><ul><li>The process leads to the formation of monomer-swollen micelles & stabilized monomer droplets. </li></ul><ul><li>Monomer swollen micelles exhibit size in the nanometric range and having large surface area in comparison to monomer droplets. </li></ul><ul><li>The polymerization reaction proceeds through nucleation & propagation stage in the process of chemical & physical initiator which initiates the polymerization chain reaction. </li></ul><ul><li>The monomer droplet act as monomer reservoir. </li></ul>
  • 18. Homogenous nucleation
  • 19. <ul><li>This mechanism is applies in cases where the monomer is sufficiently soluble in the continuous phase. </li></ul><ul><li>In this situation both the micelles & droplets play the role of monomer reservoirs. </li></ul><ul><li>When the oligomers have reached a certain length ,they ppt & form primary particles.which are stabilized by the surfactant molecules. </li></ul><ul><li>End product N.P are formed either by additional monomer input in to the primary particle or by infusion of the primary particles. </li></ul>
  • 20. Preparation of PACA N.P using emulsion polymerization process.
  • 21. <ul><li>Water insoluble monomer is emulsified in an external acid aqueous phase that contains stabilizer. </li></ul><ul><li>Anionic polymerization takes place in micelles after diffusion of monomer molecule through the water phase. </li></ul><ul><li>At neutral PH the rate of polymerization is fast leading to formation of aggregates. </li></ul><ul><li>At acidic PH i.e 2-4 the reaction rate is slow. </li></ul>
  • 22. <ul><li>The medium is stirred in order to maintain the size. </li></ul><ul><li>The water soluble drugs may be associated with PACA N.P either dissolving the drug in the aqueous polymerization medium ( or ) by incubating the blank nanospheres with an aqueous solution of drug. </li></ul><ul><li>In the later the drug molecules are physically adsorbed only on the surface. </li></ul>
  • 23. Interfacial polymerization
  • 24. <ul><li>The core phase & drug molecules to be dissolved in a volatile solvent. </li></ul><ul><li>the solution then poured in to a non-solvent for both polymer and core phase. </li></ul><ul><li>the polymer phase is separated the resultant mixture turns milky. </li></ul><ul><li>the solvent is subsequently removed under vacuum </li></ul><ul><li>nanocapsules (size 30-300 nm) </li></ul>
  • 25. N.P preparation using polymer precipitation methods <ul><li>This method is suitable for hydrophobic polymer & hydrophobic drug. </li></ul><ul><li>Depending on the solvent miscibility technique they are designated as solvent extraction / evaporation method. </li></ul>
  • 26.  
  • 27. Preparation of PLGA nanospheres <ul><li>the PLGA polymer is solubilized in a solvent (chloroform) & dispersed in a gelatin solution </li></ul><ul><li>o/w emulsion </li></ul><ul><li>nanospheres </li></ul>High speed / pressure homogenization Solvent evaporation
  • 28. Double emulsion solvent evaporation method
  • 29. Salting out <ul><li>This method is suitable for drug & polymer that are soluble in polar solvents (acetone or ethanol). </li></ul>
  • 30. Novel nanoparticulate system <ul><li>Solid lipid N.P (SLNs) </li></ul><ul><li>Suitable for i.v administration. </li></ul><ul><li>They are made of solid hydrophobic core having a mono layer of phospholipids coating. </li></ul><ul><li>The solid core contains the drug dissolved or dispersed in the solid high melting fat matrix. </li></ul><ul><li>They have potential to carry liphophilic or hydrophilic drug or diagnostics. </li></ul>
  • 31. Advantages: <ul><li>Low systemic toxicity. </li></ul><ul><li>Low cytotoxicity. </li></ul><ul><li>Large scale production is possible. </li></ul><ul><li>Not degraded by autoclaving. </li></ul><ul><li>Shows sustain release. </li></ul><ul><li>Relatively cheaper & stable. </li></ul>
  • 32. Preparation of SLNs <ul><li>Hot homogenization technique </li></ul><ul><li>melting of the lipid </li></ul><ul><li>dissolution of the drug in the melted lipid </li></ul><ul><li>mixing of the preheated dispersion medium & the drug lipid melt </li></ul><ul><li>premix using a stirrer to form a coarse pre-emulsion </li></ul><ul><li>high pressure homogenization at a temp. above the lipids melting point </li></ul>
  • 33. <ul><li>o/w nano emulsion </li></ul><ul><li>solidification of the nano-emulsion by cooling down to room temp. to form SLN. </li></ul>
  • 34. Cold homogenization technique <ul><li>melting of the lipid </li></ul><ul><li>dissolution / solubilization of the drug in the melted lipid </li></ul><ul><li>solidification of the drug loaded lipid in liquid nitrogen or dry ice </li></ul><ul><li>grinding in a power mill (50-100 μ m) </li></ul>
  • 35. <ul><li>dispersion of the lipid in the cold aqueous dispersion medium </li></ul><ul><li>solid lipid nanoparticles </li></ul>
  • 36. Hydrogel N.P: <ul><li>Hydrogel n.p are formed in water by self assemblage & self aggregation of natural polymer such as cholesteroyl dextran, cholesteroyl mannan. </li></ul><ul><li>Cholesterol groups provide cross-linking points in a non-covalent manner. </li></ul><ul><li>The size & density of hydrogel n.p can be controlled by changing the degree of substitution of cholesterol groups. </li></ul>
  • 37.  
  • 38. Nanosuspensions <ul><li>The drug powder is dispersed in an aqueous surfactant sol. By high speed stirring </li></ul><ul><li>The obtained macro-suspension is passed through a high speed homogenizer </li></ul><ul><li>Formation of n.s of the poorly water soluble drug. </li></ul>
  • 39. <ul><li>Muller & co-workers , in 2001 . Discussed mucoadhisive n.p for oral delivery & surface – modified drug n.p for site – specific delivery to brain. </li></ul>
  • 40.  
  • 41. Ph’ceutical aspects of n.p <ul><li>Three important process parameters are performed </li></ul><ul><li>Purification </li></ul><ul><li>Gel filtration </li></ul><ul><li>Dialysis </li></ul><ul><li>Ultra-centrifugation </li></ul>
  • 42. Cross – flow filtration method <ul><li>This method can be scale-up from an industrial stand point </li></ul>
  • 43. Freeze drying <ul><li>Advantages </li></ul><ul><li>Prevention from degradation / solubilization of the polymer. </li></ul><ul><li>Prevention from drug leakage , drug adsorptions , or drug degradation. </li></ul><ul><li>Easy to handle & store & help in long term preservation. </li></ul>
  • 44. sterilization <ul><li>For parenterals </li></ul><ul><li>For other delivery systems like filtration through 0.22 μ m membrane filter. (do not used always for n.p because microorganisms & n.p may be larger in size 0.25-1.0 μ m) </li></ul><ul><li>Autoclaving & γ –irradiation. </li></ul>
  • 45. Characterization of n.p <ul><li>Size & morphology </li></ul><ul><li>Two main techniques </li></ul><ul><li>photon correlation spectroscopy(PCS) </li></ul><ul><li>electron microscopy(measures the particle size & its distribution) </li></ul><ul><li>Gold coating is done for the n.p for the study of morphology. </li></ul>
  • 46. <ul><li>Specific surface area </li></ul><ul><li>The s.s area of n.p is determined with the help of sorptometer. </li></ul><ul><li>A=6/ ∂.d </li></ul><ul><li>∂ -density </li></ul><ul><li>d-diameter of particle </li></ul><ul><li>surface charge </li></ul>
  • 47. In vitro release <ul><li>N.P can be evaluated in phosphate buffer utilizing double chamber diffusion cell on a shaker stand . </li></ul><ul><li>A Millipore hydrophilic low- protein binding membrane is placed between the two chambers. </li></ul><ul><li>The donor chamber is filled with nanoparticulate suspension and the receptor chamber with plane buffer </li></ul><ul><li>The receptor chamber is assayed at different time intervals for the drug using standard procedure. </li></ul>
  • 48. Therapeutic applications of N.P Reduced toxicity,enhanced of antitumoragent Target reticuloendothelial system for intracellular infections. Poly(alkylcyanoacrylate) Poly(alkycyanoacrylate)polyesters n.p with antiviral agent. Cancer therapy Intracellular targeting purpose material application
  • 49. Enhance immune response. Enhanced bioavailability, protection from gastrointestinal enzymes. Improved retention of drug. Poly(methylmethacrylate) (oral and intramuscular immunization) Poly(methylmethacrylate)with proteins & therapeutic agent Poly(alkylcyanoacrylate)n.p with steroids,anti bacterial agent. Vaccine adjuvant Peroral absorption Ocular delivery
  • 50. Crosses blood brain barrier Improved absorption & permeation. Enzyme immunoassays. Poly(alkylcyanoacrylate)n.p with peptides. Poly(alkylcyanoacrylate)n.p for transdermal application. N.P with adsorbed enzymes. Other applications
  • 51. References…… <ul><li>S.P.vyas and R.K.khar ,controlled drug delivery-concept and advances ,Vallabh prakashan,new Delhi ,first eddition 2002 </li></ul><ul><li>N.K. jain ,controlled and novel drug delivery ,CBS publishers &distributors,new delhi. </li></ul><ul><li>Indian drugs. </li></ul><ul><li>www.google.com </li></ul>
  • 52. thank you

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