NANOCOMPOSITE PPT

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Nanocomposite for drug delivery system

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SEMINAR ON NANOCOMPOSITE FOR DRUG DELIVERY SYSTEM: 

SEMINAR ON NANOCOMPOSITE FOR DRUG DELIVERY SYSTEM By – JAYANT H. MESHRAM M. Pharm – 1 st semester (Pharmaceutics) SHARADCHANDRA PAWAR COLLGE OF PHARMACY, OTUR, DIST. -PUNE 2011-2012

Content: 

Content Introduction Structural pattern of nanocomposite Advantages of nanocomposite Formulation factors Selection of polymer Selection of drug Synthesis of nanocomposite Drug release mechanism Factor affecting drug release Conclusion Case study References

Nanoparticles – Particles having a size smaller than 100 nm. However in narrow sense less than around 10 nm also the nanoparticles in the range from nm to 1 µm called as nanoparticles in broader sense. Nanocomposite- Nanocomposites are composite materials in which the matrix material is reinforced by one or more separate nanomaterials in order to improve performance properties. The most common materials used as matrix in nanocomposites are polymers (e.g. PLGA, ). Nanocomposite – The particles comprised of many nano-scale inclusion. : 

Nanoparticles – Particles having a size smaller than 100 nm. However in narrow sense less than around 10 nm also the nanoparticles in the range from nm to 1 µm called as nanoparticles in broader sense. Nanocomposite- Nanocomposites are composite materials in which the matrix material is reinforced by one or more separate nanomaterials in order to improve performance properties. The most common materials used as matrix in nanocomposites are polymers (e.g. PLGA, ). Nanocomposite – The particles comprised of many nano -scale inclusion. Introduction

Structural pattern of nanocomposite: 

Structural pattern of nanocomposite The particles of uniform structure such as compounds made up of mutually soluble components Core shell structure consist of core particles covered by another shell components Finely dispered nanocomposites , where nanoparticles are scattered in the matrix material

Cont….: 

Cont…. Structural pattern of nanocomposite particles

Cont….: 

Cont…. Nanocomposite particle

Advantages: 

Advantages Superior to the coarser particles Drug targeting efficiency Reduces the toxicity of drug to normal cells Increase lifespan of the drug Sustain drug delivery Nanocomposite shows 2.5 fold higher uptake than 1 µm & 6 to 12 fold higher uptake than 10 µm Safe & convenient handling of toxic & potent drugs

Formulation factors: 

Formulation factors Choice of method Nature of polymer Drug intended to be use Duration of therapy Particle size requirement (10 nm – 1 µ) No toxic product

Selection of polymer: 

Selection of polymer Synthetic polymers e.g. PEG, HPMC Natural polymers e.g. Gelatin, collagen, chitosan . Either biodegradable or non biodegradable Copolymers e.g. Polylactic -co-glycolic acid (PLGA), Poly(styrene-co-2-ethyl hexylacrylate )

Selection of drug: 

Selection of drug Drug particles should be in nano size. Drug should not show polymorphism. Drug should be compatible with polymer and solvent system. Drug should be thermostable . Drug should not change its crystalline property during size reduction.

Synthesis of nanocomposite: 

Synthesis of nanocomposite Oil in oil method Gas phase method Spherical crystallization method

Oil-in-oil emulsion/Solvent evaporation method: 

Oil-in-oil emulsion/Solvent evaporation method Two oil phases were prepared 1 st oil phase- PLGA 50:50 (wt. 40000-75000) & acetonitrile (solvent) Heat for 20-30 min to dissolve PLGA in solvent Add drug to the solution Place on sonicator for about 10min for complete dispersion of drug molecules

Cont…….: 

Cont……. 2 nd oil phase 1% span 80 (surfactant) to heavy liquid (paraffin or nujol ) Place under mixer operated at 7000 rpm Add 1 st oil phase to 2 nd oil phase under mixer for 1 hr 30 min, to evaporate solvent and form nanocomposite sphere in heavy oil

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Nanocomposite collected by centrifugation at 17000 rpm Wash with n-hexane for complete removal of heavy liquid Filter the nanocomposite using 200nm filter media Cont…..

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Cont….. Specially designed high impellers connected to overhead high speed mixer Oil in oil emulsion/solvent evaporation method

Advantages : 

Advantages During nanocomposite preparation variation in size of spheres and shape due to changes in designed of impellers , viscosity, and heat generated. Disadvantages Diameter between 200nm to 1.1µm Nanocomposites are mostly rounded shape

Gas phase method: 

Gas phase method Liquid mixture of drug & polymer Fed into combustion chember Drug solution is gasified Polymeric molecules adsorbs on drug material Nanocomposite collected by rapid cooling

Advantages of gas phase method: 

Advantages of gas phase method Nanocomposite in 10 nm have been produced by this method Nanocomposite of uniform structure are produced Finely dispersed drug particles within a matrix structure are produced

Spherical crystallization method: 

Spherical crystallization method Polymer with drug is dissolved in solvent such as mixture of acetone & ethanol with stirring The solution is then introduced into water with PVA The crystallization is carry out at reduced temperature Nanocomposites are produced

Advantage of sphericle Crystallization method: 

Advantage of sphericle Crystallization method Particle size of nanocomposite range from 10nm to 200nm. Fig. PLGA nanocomposite made by the spherical crystallization method

Drug release mechanism : 

Drug release mechanism Diffusion Degradation Swelling Erosion

Diffusion : 

Diffusion Diffusion occurs when polymeric membrane dissolve in body fluids and migrate from the drug particles.

Degradation: 

Degradation Degradation is the destruction of polymeric chain. Enzymes degrades the polymer chain into lower molecular weight species that releases drug molecules. Degradation

Swelling : 

Swelling Nanocomposite in contact with body they swell to increase inside pressure & porosity of polymeric coat. Swelling is moderated by the amount of hydrophobic/hydrophilic groups & cross linking density.

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In erosion the surface of polymeric coat has been gradually destroyed due to P H and enzymatic hydrolysis causes release of the drug. Erosion Erosion

Factor affecting drug release: 

Factor affecting drug release Physicochemical properties of polymer. Size of nanocomposite. Extent of cross linking. Environment – P H , presence of enzymes.

Conclusion : 

Conclusion The better treatment of disease can be improved by the use of nanocomposite. The toxicity issue of toxic & potent drugs can be minimized to least, and nanocomposite prove their safe use. Targeted drug delivery for cancer and brain disorders can be developed for easy drug administration and improve safety of patients.

Case study: 

Case study

Introduction : 

Introduction The inhalable nanocomposite particles for treatment of lung cancer consists of , the PLGA nanoparticles loaded with anticancer drug 6-{(2-diethylamine)ethyl amino}-3-hydroxyl-7H-idenol[2,1- indon ]quinolin-7-dihydrochloride (TAS-103).

Preparation of inhalable nanocomposite of TAS-103: 

Preparation of inhalable nanocomposite of TAS-103 Step - 1 Preparation of TAS-103 loaded PLGA nanoparticles as primary particles. Step - 2 Preparation of TAS-103 loaded nanocomposite particles.

Preparation of TAS-103 loaded PLGA nanoparticles as primary particles: 

Preparation of TAS-103 loaded PLGA nanoparticles as primary particles Method – 0.1 gm of TAS-103 + 0.9 gm PLGA dissolve in 2o ml of dichloromethane. Emulsified this solution in 100 ml of 2% PVA aqueous solution using sonicator . Stir the solution to evaporate the dichloromethane. Collect the nanocomposite (200 nm) by ultracentrifugation Wash with water to remove residual PVA.

Preparation of TAS-103 loaded nanocomposite particles.: 

Preparation of TAS-103 loaded nanocomposite particles. Method- TAS-103-loaded PLGA nanocomposite particles were added to 100 ml Trehalose dehydrate solution to rich 1%. The suspensions were spray dried to prepare nanocomposite particles using a spray dryer.

Evaluation of property of TAS-103 PLGA nanocomposite particles: 

Evaluation of property of TAS-103 PLGA nanocomposite particles The density of TAS-103-loaded PLGA nanocomposite particles were measured using a pycnometer . The fine particle fraction of nanocomposite particles and primary drug loaded nanoparticles were measured using a cascade impactor . In vitro (out side the living body) Isolated lung cancer cells incubated with TAS-103 loaded nanocomposite particles. Servival cell concentration determined by uptake of 1% crystal violet.

Cont…..: 

Cont….. In vivo distribution of TAS-103 (inside the animal body) TAS-103 nanocomposite administered to rat. After certain time (10 min) blood sample and also the lungs were collected. Lung tissues were suspended into Ringer solution to calculate the inhaled concentration of drug.

Result and discussion: 

Result and discussion The FPF value of 5% TAS-103-loaded PLGA nanocomposite particles was 1.4 times higher than that of 10% TAS-103-loaded PLGA nanocomposite particles. Spray-dried samples become amorphous during the drying process thus accelerates moisture absorption. Hence, the particles absorb water inside the body and releases drug. The drug concentration in the lungs after inhalation was approx. 13 times higher than that after IV administration.

Conclusion : 

Conclusion The fine particle fraction value of 5% TAS-103-loaded PLGA nanocomposite particles were higher than that of 10% TAS-103 loaded particles. In vitro cell cyto toxicity against lung cancer cells was increased by nanocomposite . In vivo study showed that the drug concentration in lungs by inhalation of TAS-103-loaded PLGA nanocomposite was much higher than the drug concentration in plasma by IV administration of free drug. From this case study it is suggested that nanocomposite drug delivery system is effective for treatment of lung cancer.

References : 

References R. Asmatulu , A. Fakhari , H. L. Wamocha , H. Y. Chu, M. M. Eltabey “Drug carrying nanocomposite particles for Potential Drug Delivery Systems” Journal of Nanotechnology (2009) T. Yokoyama, C. C. Huang “ Nanoparticle Technology for the Production of Functional Materials” (2005) Nano -composite Polymeric Membrane System for Drug Delivery, University of Toronto Narayan Bhattarai , Jonathan Gunn, Miqin Zhang, “Advanced Drug Delivery Reviews” (2009) Anvesh Kumari , Sudesh Kumar Yadav , Subhash C. Yadav , “Biodegradable Polymeric Nanoparticles Based Drug Delivery Systems” (2010) Keishiro Tomoda , Takumi Ohkoshi , Keiji Hirita , Takehisa Nakajima, “Preparation and Properties of Inhalable Nanocomposite Particles for Treatment of Lung Cancer”(2010)

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