1. Targeted Drug Delivery System NANOPARTICLES, LIPOSOMES, RESEALED ERYTHROCYTES Presented By: Mr. Amol B. Kokate. M.Pharm 1 st year. Department Pharmaceutics

4. What is Nanotechnology? . . . .technologies, that measure, manipulate, or incorporate material or features with at least one critical dimension between ~ 1 nanometer and 100 nanometers . . . . . . whose applications exploit properties, distinct from bulk/macroscopic systems, that arise from their scale/critical dimension . . .

5. What are nanoparticles ? Coarse particle – smaller than 10 μm Fine particle – smaller than 2.5 μm Ultrafine particle – smaller than 0.1 μm (100nm) Nanoparticle – dimensions between 1 nm and 100 nm

8. Matrix type structure in which a drug is dispersed Membrane wall structure with an oil core containing drug Nanoparticles Nanospheres Nanoencapsules

9. Nanospheres and Nanocapsules

17. Aqueous protein (BSA) surfactant oil O/W emulsion Dilution with a preheated (at 100 o C) oil (heat cross linking) or addition of cross linking agent (chemical cross linking) Centrifugation and isolation of nanoparticles

24. Monomer droplet Monomer supply Monomer supply for growth Monomer bearing micelle Catalyst Nucleated micelle Stabilized polymeric nanospheres Surfactant Drug Monomer

26. Monomer droplet Stabilized polymeric nanospheres Primary particle Oligomer Activated Monomer Surfactant Drug Monomer

30. Surfactant Drug Monomer Surfactant Drug Monomer Empty micelle Stabilized polymeric nanospheres Primary particle Oligomer Activated Monomer

38. Solvent extraction, Solvent evaporation Nanoparaticles

40. Distilled water, Polaxamer 188 Mechanical stirrring Organic Solvent, Drug, polymer Aqueous phase Distilled water, Polaxamer 188 Aqueous phase Nanospheres Nanocapsules Nanoparticles preparation using Solvent Displacement method Organic phase Polar solvent, Oil Polymer, Drug Organic phase

45. Melting of the lipid Dissolution of the drug in the melted lipid Mixing of the preheated dispersion medium and the drug lipid melt Hot Homogenization Technique :

46. High pressure homogenization at a temperature above the lipids melting point O/W – nano emulsion Solidification of the nano emulsion by cooling down to room temperature to form SLN

48. Grinding in a powder mill ( 50 – 100 particles ) Dispersion of the lipid in the cold aqueous dispersion medium Solid Lipid Nanoparticles

49. Nanocrystals : Drug Dispersion with agitation Surfactant solution Milling for few hours/day Nanocrystals

50. Nanosuspension : Drug Dispersion with high speed stirring Surfactant solution High pressure homognization 1500 bar pressure Nano – suspension

52. Purification of nanoparticles : Gel filtration : Remark : High molecular weight substances and impurities are difficult to remove Schematic principle Nanoparticle Impurity

55. Purification of Nanoparticles : Cross-flow filtration technique: Nanopraticles Impurites Membrane

58. Characterization of nanoparticles : Parameter Characterization method Particle size and size distribution Charge determination Laser Doppler Anemometry Zeta potentiometer Chemical analysis of surface Static secondary ion mass spectrometry Sorptometer Carrier drug interaction Differential scanning calorimetry photon correlation spectroscopy Laser diffractometry Transmission electron microscopy Scanning electron microscopy Atomic force microscopy Drug satbility Bioassay of drug extracted from nanoparticles Chemical analysis of drug

59. In Vivo Fate and Biodistribution of Nanoparticles RES RES Phagocytosis recognition Dysopsonin adsorption Opsonin adsorption Avoidance of recognition Nanoparticle Nanoparticle

61. Nanoparticles coated with polaxomer / polaxamines. Magnetically guided nanoparticles

63. Nanotechnology – Applications Nano before Nano 2008 Nano 2012

72. Energy: Nanocrystals are an ideal light harvester photovoltaic devices. They absorb sunlight more strongly than dye molecules or bulk semiconductor material. Automobiles: In 2001, Toyota started using nanocomposites in a bumper that makes it 60 percent lighter and twice as resistant to denting and scratching. Emerging Applications

73. Sports: Wilson Double Core tennis balls have a nanocomposite coating that keeps them bouncing twice as long as an old-style ball. Clothing: Eddie Bauer is currently using embedded nanoparticles to create stain-repellent khakis. Emerging Applications

74. Effective in pancreatic cancer treatment A retroviral vector carrying cytotoxic gene Rexin-G (Epeius Biotechnology corporation) Enhance dose tolerance and hence effect elimination of solvent associated toxicity Paclitaxel (anticancer drug) bound albumin particles Abraxane (American Biosciences, Inc.) Enhanced dissolution rate& bioavailability Nanocrystallied Rapamycin (immunosuppressant) in a tablet Rapamune (Wyeth-Ayerst Laboratories) Enhanced dissolution rate & bioavailability Nanocrystal aprepiant (antiemetic) in a capsule Emend (Merck & Co. Inc.) Advantages Description Brand name

75. More powerful antibiotics Nano-sized plastic spheres with drugs (active against methicillin-resistant staph (MRSA) bacteria) chemically bonded to their surface that allow the drug to be dissolved in water. Nano-balls (Univ. of South Florida) Better protection from infection Enhance the solubility and sustained release of silver nanocrystals SILCRYST (Nucryst Pharmaceuticals) enhanced MRI images at least 25 times better than current contrast agents MRI images Trimetaspheres (Luna Nanoworks) Offer better UV protection Contains added transparent, better protecting nano zinc oxide particles Olay Moisturizers (Proctor and Gamble)