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1、20/03/2008,Dept. of Pharmaceutics,1,Nanotechnology Based Drug Delivery,Dr. Basavaraj K. Nanjwade M.Pharm., Ph.DAssociate ProfessorDepartment of PharmaceuticsJN Medical CollegeKLE UniversityBelgaum-590010,20/03/2008,

2、Dept. of Pharmaceutics,2,Applications of Nanotechnology,,20/03/2008,Dept. of Pharmaceutics,3,Targeted Drug Delivery,,20/03/2008,Dept. of Pharmaceutics,4,Nanoparticles for Drug Delivery,Metal-based nanoparticlesLipid-ba

3、sed nanoparticlesPolymer-based nanoparticlesBiological nanoparticles,20/03/2008,Dept. of Pharmaceutics,5,Nanobiopharmaceuticals,In biopharmaceuticals, in addition to the main technologies covered-liposomal, monoclona

4、l antibody-based, and polymer-based technologies host of newer technologies such as nanoparticles including various nanodimensional entities such as molecular imprinted polymers, metallofullerenes, prodrug delivery, oral

5、, injectable and implantable, pulmonary, and transdermal and transmucosal delivery have come up.,20/03/2008,Dept. of Pharmaceutics,6,Drug Delivery Technology Important to Pharma Industry,Drug delivery formulations involv

6、e low cost research compared that for discovery of new molecule, Minimizing the drug use would significantly reduce the effective cost of drug which would give financial relief to the patients,,20/03/2008,Dept. of Pha

7、rmaceutics,7,Delivery systems increase commercial opportunity by distinguishing a drug from competitive threats posed by “me too” drugs and Novel means of delivery particularly using nano-carriers, can allow branded dr

8、ugs to be rescued from abyss of generic competition (may be called “resurrection of drug”).,Drug Delivery Technology Important to Pharma Industry,20/03/2008,Dept. of Pharmaceutics,8,SOME SIGNIFICANT ACHIEVEMENTS OF NANOD

9、EVICES,Development of one dose a day ciprofloxacin using nanotechnologyTumor targeted taxol delivery using nanoparticles in Phase 2 clinical trial stageImproved ophthalmic delivery formulation using smart hydrogel na

10、noparticlesOral insulin formulation using nanoparticles carriers.Liposomal based Amphotericin B formulation,20/03/2008,Dept. of Pharmaceutics,9,CHALLENGES,Prevention of drug from biological degradationEffective Tar

11、getingPatient ComplianceCost effectivenessProduct life extension,20/03/2008,Dept. of Pharmaceutics,10,PRIORITY AREAS,Cancer Nanotechnology (i) Diagnosis using Quantum Dots (ii) Tumor T

12、argeted Delivery (iii) Imaging (iv) Cancer Gene Therapy,20/03/2008,Dept. of Pharmaceutics,11,PRIORITY AREAS,DNA Vaccines for parasitic, bacterial and viral diseasesOral and pulmonary routes for system

13、ic delivery of proteins and peptidesNanotechnology in Tissue Engineering,20/03/2008,Dept. of Pharmaceutics,12,Drug Delivery Carriers,20/03/2008,Dept. of Pharmaceutics,13,Targeting Ligands,20/03/2008,Dept. of Pharmaceut

14、ics,14,Liposome's,,,,,20/03/2008,Dept. of Pharmaceutics,15,Liposome's,Their exterior lipid bilayer is very chemically reactive, thereby providing a means to conveniently couple “tags” on a covalent basis. 

15、Such “tags” can be antibodies, antigens, cell receptors, nucleic acid probes, etc. This provides significant versatility in assay formats (i.e., immunoassay, receptor-based, nucleic acid probe, etc.) possible.

16、60;With  diameters ranging in size from approximately 50 nm to 800 nm, their aqueous core encapsulates up to millions of molecules of signal generating “markers” that can be detected in a variety of different way.

17、    A variety of different encapsulants are possible including visually detectable dyes (since the lipid bilayer is transparent), optically and fluorometrically detectable dyes, enzymes, and electroactiv

18、e compounds. This provides significant versatility in the detection schemes possible.,,20/03/2008,Dept. of Pharmaceutics,16,Niosomes,20/03/2008,Dept. of Pharmaceutics,17,Niosomes,Niosomes, non-ionic surfactant ves

19、icles, are widely studied as an alternative to liposomesThese vesicles appear to be similar to liposomes in terms of their physical propertiesThey are also prepared in the same way and under a variety of conditions,

20、from unilamellar or multilamellar structures.Niosomes alleviate the disadvantages associated with liposomes, such as chemical instability, variable purity of phospholipids and high cost.They have the potential for co

21、ntrolled and targated drug deliveryNiosomes enhanced the penetration of drugs,20/03/2008,Dept. of Pharmaceutics,18,Nanopowder,,20/03/2008,Dept. of Pharmaceutics,19,Nanopowder,Nanopowders are powders composed of nanopar

22、ticles, that is particles having an average diameter below 50 nanometers (nm). A jar of a true nanopowder when emptied from chest height to toward the floor will disperse into the air before reaching the floor. Most

23、manufacturers of “nanopowders” produce micropowder assemblies of nanoparticles but the powder itself is rarely a nanopowder. Such compounds have two or more different cations (positively charged elements) in their chem

24、ical formula. An example of a complex compound is calcium titanate (CaTiO3).,20/03/2008,Dept. of Pharmaceutics,20,Nanocluster,,20/03/2008,Dept. of Pharmaceutics,21,Nanocluster,One of the central themes in nanoscience res

25、earch is to synthesize high quality nanoparticles with precise control over particle size, shape, structure, and composition. For inorganic nanoparticles (e.g. metal and semiconductor), two regimes are of particular in

26、terest, that is, nanoclusters in a size range from subnanometer to ~2 nm and nanocrystals (typically 2-100 nm).,20/03/2008,Dept. of Pharmaceutics,22,Nanocrystals,20/03/2008,Dept. of Pharmaceutics,23,Nanocrystals,When the

27、 size of the material is reduced to less than 100 nanometers, the realm of quantum physics takes over and materials begin to demonstrate entirely new properties. Nano-design of drugs by various techniques like milling,

28、 high pressure homogenization, controlled precipitation etc., are explored to produce, drug nanocrystals, nanoparticles, nanoprecipitates, nanosuspensions (which for ease of understanding commonly mentioned as nanocrysta

29、ls).  As decreased size will increase the solubility of drugs hence, this technology is explored to increase oral bioavailability of sparingly water soluble drugs.,20/03/2008,Dept. of Pharmaceutics,24,Micelle,,20/

30、03/2008,Dept. of Pharmaceutics,25,Micelle,Micelle is an aggregate of amphipathic molecules in water, with the nonpolar portions in the interior and the polar portions at the exterior surface, exposed to water. Amphiphi

31、lic molecules form micelle above a particular concentration which is called as critical micellar concentration (CMC).  Micelles are known to have an anisotropic water distribution within their structure, means

32、60;water concentration decreases from the surface towards the core of the micelle, with a completely hydrophobic (water-excluded) core. Hydrophobic drugs can be encapsulated/solubalized, into inner core. The spatial

33、position of a solubilized drug in a micelle will depend on its polarity, nonpolar molecules will be solubilized in the micellar core, and substances with intermediate polarity will be distributed along the surfactant mol

34、ecules in certain intermediate positions.,20/03/2008,Dept. of Pharmaceutics,26,Dendrimers,,20/03/2008,Dept. of Pharmaceutics,27,Dendrimers,These branched macromolecules are constructed around a simple core unit. Dendr

35、imers have a high degree of molecular uniformity, narrow molecular weight distribution, specific size and shape characteristics, and a highly- functionalized terminal surface. The manufacturing process is a series of

36、repetitive steps starting with a central initiator core. Each subsequent growth step represents a new "generation" of polymer with a larger molecular diameter, twice the number of reactive surface sites, and a

37、pproximately double the molecular weight of the preceding generation.,20/03/2008,Dept. of Pharmaceutics,28,Polymeric Nanoparticles,20/03/2008,Dept. of Pharmaceutics,29,Polymeric Nanoparticles,In recent years, biodegradab

38、le polymeric nanoparticles have attracted considerable attention as potential drug delivery devices in view of their applications in drug targeting to particular organs/tissues, as carriers of DNA in gene therapy, and i

39、n their ability to deliver proteins, peptides and genes through a per oral route of administration.,20/03/2008,Dept. of Pharmaceutics,30,Carbon 60,20/03/2008,Dept. of Pharmaceutics,31,Carbon 60,C60 are spherical molecul

40、es about 1nm in diameter, comprising 60 carbon atoms arranged as 20 hexagons and 12 pentagons: the configuration of a football. Hence they find application as NanoPharmaceuticals with large drug payload in their cage

41、like structure. On the other hand with development of various chemical substitutes for C60, it is possible to develop functionalized C60 with better drug targeting properties,20/03/2008,Dept. of Pharmaceutics,32,Carbon

42、 Nanotube,20/03/2008,Dept. of Pharmaceutics,33,Carbon Nanotube,Carbon nanotubes are adept at entering the nuclei of cells and may one day be used to deliver drugs and vaccines. The modified nanotubes have so far only b

43、een used to ferry a small peptide into the nuclei of fibroblast cells. But the researchers are hopeful that the technique may one day form the basis for new anti-cancer treatments, gene therapies and vaccines.,20/03/20

44、08,Dept. of Pharmaceutics,34,Equipments for Nanoparticles,,HomogenizerUltra SonicatorMillsSpray MillingSupercritical Fluid TechnologyElectrosprayUltracentrifugationNanofiltration,20/03/2008,Dept. of Pharmaceutics,