Intelligent Drug Delivery Systems 30 8 2011

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Intelligent Drug Delivery Systems: 

Intelligent Drug Delivery Systems -: Prepared by :- Vora Vipul D. M.Pharm Semester- III Enr No. -102100808001 Novel Drug Delivery System – II (930102) Department of Pharmaceutics Atmiya Inistitute of Pharmacy,Rajkot

CONTENTS: 

CONTENTS Introduction to IDDS Types of IDDS Pulsatile Systems Responsive systems Systems Based on Enzymes System Based on Antibody Interactions System Based on Chelation 2 27/08/2011

INTRODUCTION: 

INTRODUCTION Intelligent Drug Delivery System (IDDS) have been developed to deliver drug effectively to the targeting site Targeted Site-specific delivery The release of the drug is required to… Temporal control Self-regulating drug delivery 3 27/08/2011

How It Is Work: 

How It Is Work It senses the signal caused by disease (SENSOR FUNCTION) Judges the magnitude of signal (PROCESSOR FUNCTION ) Then act to release the drug in direct response (EFFECTOR FUNCTION) 4 27/08/2011

Continue: 

Continue 5 27/08/2011

PULSATILE SYSTEMS: 

PULSATILE SYSTEMS Electrically Regulated Systems Photoresponsive Systems Ultrasonically Modulated Systems Magnetically Modulated Systems 6 27/08/2011

PULSATILE SYSTEMS: 

PULSATILE SYSTEMS 7 27/08/2011 Electrically Regulated Systems Drug is release under the effect of an applied electric field D ue to action of an applied electric field on rate limiting membrane or directly on the solute thereby controlling its transport across the membrane. Eg . Electric field-sensitive polyelectrolyte hydrogels Insulin was released from poly-(dimethyl aminopropyl acrylamide) (PDMAPAA) gel.

PULSATILE SYSTEMS: 

PULSATILE SYSTEMS 8 27/08/2011 Photoresponsive Systems Photoresponsive gels change their physical or chemical characteristics reversibly upon exposure to photoradiation . The photochromic molecules capture the optical signal and subsequent isomerisation of the chromophores in the photoreceptors converts it to a chemical signal . Eg . Copolymer gels of N-isopropyl acrylamide and a photosensitive molecule, bis (4-dimethyl amino phenyl)(4-vinyl phenyl) methyl leucocyanide .

PULSATILE SYSTEMS: 

PULSATILE SYSTEMS 9 27/08/2011 Ultrasonically Modulated Systems The feasibility of ultrasonic-controlled polymeric delivery systems in which release rates of substances can be repeatedly modulated externally Eg . The bioerodible polymers - polylactide , polyglycolide Non-erodible systems - Zinc bovine insulin from ethylene vinyl acetate copolymer

PULSATILE SYSTEMS: 

PULSATILE SYSTEMS 10 27/08/2011 Magnetically Modulated Systems This approach involves incorporation of magnetic beads in elastic polymers. It has been shown that when oscillating magnetic field is applied, more drug will be released. Eg. Insulin and other macromolecular bioactives can be continuously released by embedding them in a carrier like ethylene vinyl acetate copolymer (EVAc).

RESPONSIVE SYSTEMS: 

RESPONSIVE SYSTEMS pH Sensitive Systems Thermosensitive Systems Inflammation Responsive Systems Glucose and other Saccharide Sensitive Systems 11 27/08/2011

RESPONSIVE SYSTEMS: 

RESPONSIVE SYSTEMS pH Sensitive Systems The pH range of different parts of gastrointestinal tract may provide environmental stimuli for ph sensitive systems Eg. pH sensitive bioerodible polymer approach Enzyme substrate interaction produces a pH chang Poly acidic polymers Polybasic polymers 12 27/08/2011

RESPONSIVE SYSTEMS: 

RESPONSIVE SYSTEMS Thermosensitive Systems Thermosensitive polymers Polymer water interaction Polymer-polymer interaction along with polymer water interaction Eg. Cross linking polymers which exhibit an Lower Critical Solution Temperature (LCST) Polyethylene oxide (PEO), HPC, PVA and derivatives of poly(N-substituted acrylamides). 13 27/08/2011

RESPONSIVE SYSTEMS: 

RESPONSIVE SYSTEMS Inflammation Responsive Systems It is based on the biodegradable hydrogels of cross-linked hyaluronic acid Hyaluronic acid is specifically degraded by hydroxyl radicals produced by phagocytic cells like leukocytes and macrophages, locally at the inflammatory sites . This approach involves dispersion of drug loaded lipid microspheres into degradable matrices of cross-linked hyaluronic acid. 14 27/08/2011

RESPONSIVE SYSTEMS: 

RESPONSIVE SYSTEMS Glucose and other Saccharide Sensitive Systems Based on the principle of competitive and complementary binding behavior of Conconavalin A (CON-A) with Glucose & Glycosylated Insulin (G-INSULIN) POLY(HYDROXYETHYL METHACRYLATE) POUCHES (PHEMA) which contain a G-INSULIN-CON A complex suspension Hydrophobic Nylon Microcapsule showed quick ‘ON-OFF’ response of insulin release. Glucose sensitive insulin delivery system based on a sol-gel transition 15 27/08/2011

Systems Based on Enzymes: 

Systems Based on Enzymes Urea Responsive Delivery Systems Glucose Responsive Insulin Delivery Systems Morphine Triggered Naltrexone Delivery Systems 16 27/08/2011

Systems Based on Enzymes: 

Systems Based on Enzymes Urea Responsive Delivery Systems The alteration in local pH by immobilization of enzymes that lead to changes in polymer erosion rates. This system is based on the conversion of urea to NH 4 HCO 3 and NH 4 OH by the action of urease that increases the pH Eg . A partially esterified copolymer of methyl vinyl ether and maleic anhydride developed that displayed a pH dependent drug release. This polymer dissolves by ionization of the carboxylic groups 17 27/08/2011

Systems Based on Enzymes: 

Systems Based on Enzymes Morphine Triggered Naltrexone Delivery System Naltrexone is a long acting opiate antagonist that blocks opiate-induced euphoria and thus used for treatment of heroin addiction Activation of the device is based on the reversible inactivation of enzymes obtained by the covalent attachment of hapten 18 27/08/2011

System Based on Antibody Interactions: 

System Based on Antibody Interactions This approach has proposed antibody mediated release of contraceptive agent The β subunit of Human Chronic Gonadotropin (HCG) is grafted on to the surface of the polymer, which in turn is exposed to antibodies to β –HCG. The appearance of HCG in the blood (indication of pregnancy) will cause release of contraceptive drug as HCG competes for the polymer bound antibodies to HCG and initiates the drug release 19 27/08/2011

System Based on Chelation: 

System Based on Chelation The concept is based on the property of metals to accelerate the hydrolysis of carboxylate or phosphate esters and amides Tagging of the chelator to a polymer chain by a covalent ester or amide link prevents its premature loss by excretion and reduces its toxic effects. In the presence of specific ion, the bound chelating agent forms a complex followed by metal accelerated hydrolysis and subsequent elimination of the metal chelate 20 27/08/2011

References: 

References Weinstein, J.N. Liposomes in the diagnosis and treatment of cancer. In: M.J. Ostro (Ed.),Liposomes from Biophysics to Therapeutics, Marcel Dekker, Inc., New York, pp. 40-101. Yokoyama, M., Miyauchi, M., Yamada, N., Okano, T., Kataoka, K. and Inoue, S. Polymer micelles as novel drug carrier: Adriamycin-conjugated poly(ethylene glycol)-poly(aspartic acid) block copolymer. J. Control. Release ll, 269-278. Hirokawa, Y. and Tanaka, T. Volume phase transition in a nonionic gel. J. Chem. Phys. 81, 6379-6380. Tanaka, T. Gels. Sci. Am. 244, 124-138. 21 27/08/2011

References: 

References Tanaka, T. Collapse of gels and the critical endpoint. Phys. Rev. Lett. 40, 820-823. Irie, M. and Kunwatchakun, D. Photoresponsive polymers. 8. Reversible photostimulated dilation of polyacrylamide gels having triphenylmethane leuco derivatives. Macromolecules 19, 2476-2480. Hoffman, A.S. Applications of thermally reversible polymers and hydrogels in therapeutics and diagnostics. J. Control. Release 6, 297-305. Osada, Y. and Hasebe, M. Electrically activated mechanochemical devices using polyelectrolyte gels. Chem. Lett. 9, 1285-1288. 22 27/08/2011

Questions: 

Questions 23 27/08/2011

Slide 24: 

Thank You 24 27/08/2011