title: Potential applications of polymeric microsphere suspension as subcutaneous depot for insulin.
abstract: The objective of this investigation was to develop an injectable, depot-forming drug delivery system for insulin based on microparticle technology to maintain constant plasma drug concentrations over prolonged period of time for the effective control blood sugar levels. Formulations were optimized with two well-characterized biodegradable polymers namely, poly(DL-lactide-co-glycolide) and poly-epsilon-caprolactone and evaluated in vitro for physicochemical characteristics, drug release in phosphate buffered saline (pH 7.4), and evaluated in vivo in streptozotocin-induced hypoglycemic rats. With a large volume of internal aqueous phase during w/o/w double emulsion solvent evaporation process and high molecular weight of the polymers used, we could not achieve high drug capture and precise control over subsequent release within the study period of 60 days. However, this investigation revealed that upon subcutaneous injection, the biodegradable depot-forming polymeric microspheres controlled the drug release and plasma sugar levels more efficiently than plain insulin injection. Preliminary pharmacokinetic evaluation exhibited steady plasma insulin concentration during the study period. These formulations, with their reduced frequency of administration and better control over drug disposition, may provide an economic benefit to the user compared with products currently available for diabetes control.
authors.affiliation: Dr. T. M. A. Pai Pharmaceutical Research Centre, College of Pharmaceutical Sciences, Manipal, Karnataka, India. shenoydin@yahoo.com
authors.forename: Dinesh B
authors.initials: DB
authors.lastname: Shenoy
authors.forename: Reshma J
authors.initials: RJ
authors.lastname: D'Souza
authors.forename: Sandip B
authors.initials: SB
authors.lastname: Tiwari
authors.forename: N
authors.initials: N
authors.lastname: Udupa
mesh_terms: D000818:Animals; D019540:Area Under Curve; D001786:Blood Glucose / Q000187:drug effects; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000097:blood; D004337:Drug Carriers / Q000737:chemistry; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology; D019344:Lactic Acid / Q000737:chemistry; D008297:Male; D008863:Microspheres; D011091:Polyesters / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013535:Suspensions
chemical_list: D001786:Blood Glucose; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D007328:Insulin; D011091:Polyesters; D011108:Polymers; D013535:Suspensions; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; C016240:polycaprolactone; D011100:Polyglycolic Acid; D019344:Lactic Acid