Development and in-vivo evaluation of insulin-loaded chitosan phthalate microspheres for oral delivery.
Novel chitosan phthalate microspheres containing insulin were prepared by emulsion cross-linking technique. The feasibility of these microspheres as oral insulin delivery carriers was evaluated. The pH-responsive release behaviour of insulin from microspheres was analysed. The ability of chitosan phthalate-insulin microspheres to enhance intestinal absorption and improve the relative pharmacological availability of insulin was investigated by monitoring the plasma glucose and insulin level of streptozotocin-induced diabetic rats after oral administration of microspheres at insulin dose of 20 IU kg(-1). In simulated gastric fluid (pH 2.0), insulin release from the microspheres was very slow. However, as the pH of the medium was changed to simulated intestinal fluid (pH 7.4), a rapid release of insulin occurred. The relative pharmacological efficacy for chitosan phthalate microspheres (18.66 +/- 3.84%) was almost four-fold higher than the efficacy of the chitosan phthalate-insulin solution administration (4.08 +/- 1.52%). Chitosan phthalate microspheres sustained the plasma glucose at pre-diabetic level for at least 16 h. These findings suggest that the microsphere is a promising carrier as oral insulin delivery system.
Ubaidulla
Udhumansha
U
Department of Pharmaceutics, Faculty of Pharmacy, Hamdard University, New Delhi, India. ubaidnkl@gmail.com
Khar
Roop Kishan
RK
Ahmed
Farhan Jalees
FJ
Panda
Amulya Kumar
AK
D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry*; D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D004337:Drug Carriers / Q000737:chemistry*; D004655:Emulsions; D005750:Gastric Juice / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D007328:Insulin / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology; D007408:Intestinal Absorption; D007419:Intestinal Secretions / Q000378:metabolism; D008297:Male; D008863:Microspheres; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin
D001786:Blood Glucose; D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004655:Emulsions; D007004:Hypoglycemic Agents; D007328:Insulin; C119691:chitosan phthalate; D013311:Streptozocin; D048271:Chitosan