Approaches for enhancing oral bioavailability of peptides and proteins.
Approaches for enhancing oral bioavailability of peptides and proteins.
复制标题
DOI：
10.1016/j.ijpharm.2013.02.030
复制
发表时间：
2013-04-15
影响因子：
5.8
通讯作者：
Mitra, Ashim K.
中科院分区：
文献类型：
--
作者：
Renukuntla, Jwala;Vadlapudi, Aswani Dutt;Patel, Ashaben;Boddu, Sai H. S.;Mitra, Ashim K.
多肽和蛋白质药物的口服给药面临着巨大的挑战，部分原因是胃肠道(GI)环境。尽管工业和学术实验室做出了相当大的努力，但在多肽和蛋白质的有效口服给药方面并没有取得重大突破。口服时，胃肠道上皮起到吸收蛋白质的物理和生化屏障的作用，导致生物利用度低(通常不到1-2%)。理想的口服给药系统应该能够a)保持蛋白质分子的完整性，直到它到达吸收部位，b)在目标吸收部位释放药物，释放系统通过特定的相互作用附着到该部位，以及c)保留在胃肠道内，而不考虑其短暂的限制。人们已经探索了各种技术来克服与口服胰岛素、促性腺激素释放激素、降钙素、人类生长因子、疫苗、脑啡肽和干扰素等大分子相关的问题，但所有这些技术都取得了有限的成功。本文综述了多肽和蛋白质口服给药的生理障碍，以及规避这些障碍和提高这些大分子的口服生物利用度的新的药物途径。
Oral delivery of peptide and protein drugs faces immense challenge partially due to the gastrointestinal (GI) environment. In spite of considerable efforts by industrial and academic laboratories, no major breakthrough in the effective oral delivery of polypeptides and proteins has been accomplished. Upon oral administration, gastrointestinal epithelium acts as a physical and biochemical barrier for absorption of proteins resulting in low bioavailability (typically less than 1–2%). An ideal oral drug delivery system should be capable of a) maintaining the integrity of protein molecules until it reaches the site of absorption, b) releasing the drug at the target absorption site, where the delivery system appends to that site by virtue of specific interaction, and c) retaining inside the gastrointestinal tract irrespective of its transitory constraints. Various technologies have been explored to overcome the problems associated with the oral delivery of macromolecules such as insulin, gonadotropin-releasing hormones, calcitonin, human growth factor, vaccines, enkephalins, and interferons, all of which met with limited success. This review article intends to summarize the physiological barriers to oral delivery of peptides and proteins and novel pharmaceutical approaches to circumvent these barriers and enhance oral bioavailability of these macromolecules.
登录
查看更多内容
影响因子：
3.7
作者：
Cheng, JJ;Teply, BA;Langer, RS
通讯作者：
Langer, RS
DOI：
10.1006/bbrc.1993.1114
发表时间：
1993-02-15
影响因子：
3.1
作者：
BURTON, PS;CONRADI, RA;HO, NFH
通讯作者：
HO, NFH
影响因子：
3.8
作者：
Burton, PS;Conradi, RA;Borchardt, RT
通讯作者：
Borchardt, RT
影响因子：
10.8
作者：
Bernkop-Schnurch, A;Krajicek, ME
通讯作者：
Krajicek, ME
影响因子：
24.5
作者：
CATNACH, SM;FAIRCLOUGH, PD;HAMMOND, SM
通讯作者：
HAMMOND, SM