title: Delivery of Exenatide and Insulin Using Mucoadhesive Intestinal Devices.
abstract: A major disadvantage associated with current diabetes therapy is dependence on injectables for long-term disease management. In addition to insulin, incretin hormone replacement therapies including exenatide have added a new class of drugs for Type-2 diabetes. Although efficacious, patient compliance with current diabetic therapy is poor due to requirement of injections, inability to cross the intestinal epithelium and instability in the gastrointestinal tract. Here, we report the efficacy of a mucoadhesive device in providing therapeutic concentrations of insulin and exenatide via oral administration. Devices were prepared with a blend of FDA-approved polymers, carbopol, pectin and sodium carboxymethylcellulose, and were tested for drug carrying capability, in vitro release, Caco-2 permeability, and in vivo efficacy for insulin and exenatide. Results suggested that mucoadhesive devices successfully provided controlled release of FITC-insulin, released significant amounts of drug, while providing noteworthy enhancement of drug transport across Caco-2 monolayers without compromising monolayer integrity. In-vivo administration of the devices provided significant enhancement of drug absorption with 13- and 80-fold enhancement of relative bioavailability for insulin and exenatide compared to intestinal injections with significant increase in half-lives, thus resulting in prolonged blood glucose reduction. This study validates the efficacy of mucoadhesive devices in promoting oral peptide delivery to improve patient compliance and dose adherence.
authors: Department of Chemical Engineering, University of California, Santa Barbara, CA, 93106, USA.|School of Pharmacy, Keck Graduate Institute, 535 Watson Dr., Claremont, CA, 91711, USA.
authors: Vivek
authors: V
authors: Gupta
authors: Department of Chemical Engineering, University of California, Santa Barbara, CA, 93106, USA.
authors: Byeong-Hee
authors: BH
authors: Hwang
authors: Department of Chemical Engineering, University of California, Santa Barbara, CA, 93106, USA.
authors: Nishit
authors: N
authors: Doshi
authors: Department of Chemical Engineering, University of California, Santa Barbara, CA, 93106, USA.
authors: Amrita
authors: A
authors: Banerjee
authors: Department of Chemical Engineering, University of California, Santa Barbara, CA, 93106, USA.
authors: Aaron C
authors: AC
authors: Anselmo
authors: Department of Chemical Engineering, University of California, Santa Barbara, CA, 93106, USA. samir@engineering.ucsb.edu.
authors: Samir
authors: S
authors: Mitragotri
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D002417:Cattle; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D000077270:Exenatide; D006801:Humans; D007328:Insulin / Q000493:pharmacokinetics / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000378:metabolism*; D010455:Peptides / Q000493:pharmacokinetics / Q000494:pharmacology; D014688:Venoms / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D007328:Insulin; D010455:Peptides; D014688:Venoms; D000077270:Exenatide
keywords: Absorption enhancement; Exenatide; Insulin; Oral delivery; Peptides; Type-2 diabetes