Shiva(Nanoparticles)

5,400 views

Published on

Published in: Education, Technology, Business
5 Comments
5 Likes
Statistics
Notes
  • u have prepared really very nice presentation......plz send it to me on hdeep922@gmail .com
       Reply 
    Are you sure you want to  Yes  No
    Your message goes here
  • nice work...
       Reply 
    Are you sure you want to  Yes  No
    Your message goes here
  • very nice
       Reply 
    Are you sure you want to  Yes  No
    Your message goes here
  • sir, nice presentation
       Reply 
    Are you sure you want to  Yes  No
    Your message goes here
  • Resp.sir u have prepared really nice presentation...plz send me your presentation on gautam.gurjar@gmail..com
    its humble req sir
       Reply 
    Are you sure you want to  Yes  No
    Your message goes here
No Downloads
Views
Total views
5,400
On SlideShare
0
From Embeds
0
Number of Embeds
14
Actions
Shares
0
Downloads
532
Comments
5
Likes
5
Embeds 0
No embeds

No notes for slide

Shiva(Nanoparticles)

  1. 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. 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. 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. 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. 5. Natural hydrophilic polymers Alginate Daxtran Chitosan Agarose Pullulan Gelatin Albumin Lectins Legumin vicilin polysaccharides Proteins
  6. 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. 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. 8. Cross linking in w/o emulsion
  9. 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. 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. 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. 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. 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. 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. 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. 16. Micellar nucleation:
  17. 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. 18. Homogenous nucleation
  19. 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. 20. Preparation of PACA N.P using emulsion polymerization process.
  21. 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. 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. 23. Interfacial polymerization
  24. 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. 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
  27. 28. Double emulsion solvent evaporation method
  28. 29. Salting out <ul><li>This method is suitable for drug & polymer that are soluble in polar solvents (acetone or ethanol). </li></ul>
  29. 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>
  30. 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>
  31. 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>
  32. 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>
  33. 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>
  34. 35. <ul><li>dispersion of the lipid in the cold aqueous dispersion medium </li></ul><ul><li>solid lipid nanoparticles </li></ul>
  35. 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>
  36. 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>
  37. 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>
  38. 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>
  39. 42. Cross – flow filtration method <ul><li>This method can be scale-up from an industrial stand point </li></ul>
  40. 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>
  41. 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>
  42. 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>
  43. 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>
  44. 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>
  45. 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
  46. 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
  47. 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
  48. 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>
  49. 52. thank you

×