期刊
JOURNAL OF CONTROLLED RELEASE
卷 172, 期 3, 页码 753-762出版社
ELSEVIER
DOI: 10.1016/j.jconrel.2013.09.004
关键词
Oral; Macromolecule; Patch; Peroral; Intestinal; Enteric coated capsule
资金
- Otis Williams Fellowship from the Santa Barbara Foundation
- National Science Foundation Graduate Research Fellowship [DGE-1144085]
- MRSEC Program of the NSF [DMR 1121053]
- NSF
- Entrega Inc.
One of the major challenges faced by therapeutic polypeptides remains their invasive route of delivery. Oral administration offers a potential alternative to injections; however, this route cannot be currently used for peptides due to their limited stability in the stomach and poor permeation across the intestine. Here, we report mucoadhesive devices for oral delivery that are inspired by the design of transdermal patches and demonstrate their capabilities in vivo for salmon calcitonin (sCT). The mucoadhesive devices were prepared by compressing a polymeric matrix containing carbopol, pectin and sodium carboxymethylcellulose (1:1:2), and were coated on all sides but one with an impermeable and flexible ethyl cellulose (EC) backing layer. Devices were tested for in vitro dissolution, mucoadhesion to intestinal mucosa, enhancement of drug absorption in vitro (Caco-2 monolayer transport) and in vivo in rats. Devices showed steady drug release with approximate to 75% cumulative drug released in 5 h. Devices also demonstrated strong mucoadhesion to porcine small intestine to withstand forces up to 100 times their own weight. sCT-loaded mucoadhesive devices exhibited delivery of sCT across Caco-2 monolayers and across the intestinal epithelium in vivo in rats. A approximate to 52-fold (pharmacokinetic) and approximate to 44-fold (pharmacological) enhancement of oral bioavailability was observed with mucoadhesive devices when compared to direct intestinal injections. Oral delivery of devices in enteric coated capsules resulted in significant bioavailability enhancement. (C) 2013 Elsevier B.V. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据