| Evaluation of polyanhydride microspheres for basal insulin delivery: Effect of copolymer composition and zinc salt on encapsulation, in vitro release, stability, in vivo absorption and bioactivity in diabetic rats. | |
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MedLine Citation:
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PMID: 19472196 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The potential of poly 1,3-bis-(p-carboxyphenoxy) propane-co-sebacic acid (p(CPP:SA)) microspheres was investigated for controlled delivery of basal insulin. CPP:SA copolymers with molar compositions of 20:80, 40:60, and 50:50 were synthesized, characterized, and used in the fabrication of microspheres by water-in-oil-in-water double emulsion solvent evaporation technique. Insulin stability was assessed using various analytical methods and in vivo insulin absorption and bioactivity were studied in diabetic rats. Microspheres exhibited smooth surfaces and mean particle size ranged from 41.5 to 49.8 microm. Insulin encapsulation efficiency (EE) and in vitro release kinetics were influenced by the molar ratios of CPP:SA copolymer. Increasing CPP content and addition of zinc oxide increased EE, reduced burst release, and prolonged insulin in vitro release over a month. Dimer aggregates were observed for insulin encapsulated in CPP:SA 50:50 microspheres and addition of zinc oxide prevented dimer formation. Subcutaneous administration of CPP:SA 50:50 microspheres in diabetic rats controlled insulin release over a month, and the released insulin was bioactive as determined by lowering blood glucose levels. The results indicate that CPP:SA microspheres controlled insulin release in vitro and in vivo over a month and the released insulin was conformationally and chemically stable, and bioactive. |
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Authors:
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Chandrasekar Manoharan; Jagdish Singh |
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Publication Detail:
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Type: Evaluation Studies; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of pharmaceutical sciences Volume: 98 ISSN: 1520-6017 ISO Abbreviation: J Pharm Sci Publication Date: 2009 Nov |
Date Detail:
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Created Date: 2009-10-01 Completed Date: 2010-01-14 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985195R Medline TA: J Pharm Sci Country: United States |
Other Details:
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Languages: eng Pagination: 4237-50 Citation Subset: IM |
Copyright Information:
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(c) 2009 Wiley-Liss, Inc. and the American Pharmacists Association |
Affiliation:
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Department of Pharmaceutical Sciences, College of Pharmacy, Nursing, and Allied Sciences, North Dakota State University, Fargo, North Dakota 58105, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Absorption Animals Blood Glucose / metabolism Chemistry, Pharmaceutical Diabetes Mellitus, Experimental / drug therapy Drug Carriers / chemistry Drug Compounding Drug Delivery Systems Drug Stability Hypoglycemic Agents / chemistry* Insulin / analogs & derivatives*, chemistry Kinetics Male Microscopy, Electron, Scanning Microspheres* Molecular Structure Molecular Weight Particle Size Polyanhydrides / chemistry* Polymers / chemical synthesis, chemistry Rats Rats, Sprague-Dawley Technology, Pharmaceutical / methods Zinc Compounds / chemistry* |
| Chemical | |
Reg. No./Substance:
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0/Blood Glucose; 0/Drug Carriers; 0/Hypoglycemic Agents; 0/Polyanhydrides; 0/Polymers; 0/Zinc Compounds; 0/basal insulin; 11061-68-0/Insulin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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