Concanavalin A conjugated biodegradable nanoparticles for oral insulin delivery
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RESEARCH PAPER
Concanavalin A conjugated biodegradable nanoparticles for oral insulin delivery Pooja Hurkat • Aviral Jain • Ashish Jain • Satish Shilpi • Arvind Gulbake • Sanjay K. Jain
Received: 27 May 2012 / Accepted: 24 September 2012 / Published online: 10 October 2012 Ó Springer Science+Business Media Dordrecht 2012
Abstract Major research issues in oral protein delivery include the stabilization of protein in delivery devices which could increase its oral bioavailability. The study deals with development of oral insulin delivery system utilizing biodegradable poly(lacticco-glycolic acid) (PLGA) nanoparticles and modifying its surface with Concanavalin A to increase lymphatic uptake. Surface-modified PLGA nanoparticles were characterized for conjugation efficiency of ligand, shape and surface morphology, particle size, zeta potential, polydispersity index, entrapment efficiency, and in vitro drug release. Stability of insulin in the developed formulation was confirmed by SDSPAGE, and integrity of entrapped insulin was assessed using circular dichroism spectrum. Ex vivo study was performed on Wistar rats, which exhibited the higher intestinal uptake of Con A conjugated nanoparticles. In vivo study performed on streptozotocin-induced diabetic rats which indicate that a surface-modified nanoparticle reduces blood glucose level effectively within 4 h of its oral administration. In conclusion, the present work resulted in successful production of Con A NPs bearing insulin with sustained release profile, and better absorption and stability. The Con A NPs
P. Hurkat A. Jain A. Jain S. Shilpi A. Gulbake S. K. Jain (&) Pharmaceutics Research Projects Laboratory, Department of Pharmaceutical Sciences, Dr. Hari Singh Gour Vishwavidyalaya, Sagar 470003, MP, India e-mail: [email protected]
showed high insulin uptake, due to its relative high affinity for non-reducing carbohydrate residues i.e., fucose present on M cells and have the potential for oral insulin delivery in effective management of Type 1 diabetes condition. Keywords Concanavalin A Biodegradable nanoparticles Protein PLGA Insulin Oral delivery
Introduction Diabetes mellitus was known in antiquity and remains today a worldwide and increasing health problem. It occurs because of lack of insulin, with or without factors that oppose the action of insulin. The beta cells of pancreas are decreased in number or are degranulated in diabetes. The reduction in number of beta cells corresponds to the lack of insulin. In Type1 diabetes there are no beta cells, in Type 2 diabetes only about one half of them are present. Although insulin deficiency is the primary defect in IDDM (Insulin dependent diabetes mellitus), in patients with poorly controlled IDDM there is also a defect in the ability of target tissues to respond to the administration of insulin. IDDM patients require insulin to keep their blood sugar levels under tight control. The need for regular daily injections is a major drawback for diabetic
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