Controlling Gastric Delivery of a GIP/GLP1 Peptide in Monkeys by Mucoadhesive SNAC Tablets.

IF 3.5 3区医学 Q2 CHEMISTRY, MULTIDISCIPLINARY

Pharmaceutical Research Pub Date : 2025-06-01 Epub Date: 2025-06-13 DOI:10.1007/s11095-025-03881-9

Huyen Tran, Jennifer Martin, Mridula Dogra, Jenna Walker, Donald Risley, Aktham Aburub

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引用次数: 0

Abstract

Objective: Gastric delivery has been utilized for oral delivery of peptides. However, target site of the delivery is uncontrollable due to the housekeeping wave. In addition, dilution and spreading of peptides and permeation enhancers in the stomach may limit the oral peptide bioavailability. In this study, we developed mucoadhesive tablets containing SNAC and a GIP/GLP1 dual agonist peptide (LY) to localize the peptide delivery and minimize the dilution effect in the stomach.

Methods: The mucoadhesive tablets were prepared as bilayer or trilayer tablets with sodium alginate on one or both sides of the formulation layer (LY/SNAC). Mucoadhesion tests were conducted using a rotating cylinder mounted with isolated rat and minipig gastric tissues, and in vivo in monkeys. Oral bioavailability of the peptide was determined in monkeys via oral administration of the mucoadhesive tablets.

Results: The mucoadhesive tablets dissolved > 80% within 15 min at pH 6.8. The trilayer SNAC tablets adhered to the isolated gastric tissues. Following oral administration to monkeys, 10/10 mucoadhesive tablets were retained in the monkey stomach 10-20 min post-dose compared to 1/3 SNAC control tablets. Oral bioavailability of LY peptide was of similar magnitude as that achieved with the SNAC control tablet. In vivo dissolution of the mucoadhesive tablets was slower than the control tablets leading to lower SNAC concentration at the tablet site in the monkey stomach.

Conclusion: These data suggest that the mucoadhesive tablets improved gastric retention but did not increase oral bioavailability of the LY peptide following gastric delivery in monkeys.

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黏附SNAC片控制猴子胃中GIP/GLP1肽的传递。

目的：胃给药已被用于多肽的口服给药。然而，由于内务波的存在，配送的目标地点是不可控的。此外，肽的稀释和扩散以及胃中的渗透增强剂可能会限制口服肽的生物利用度。在这项研究中，我们开发了含有SNAC和GIP/GLP1双激动剂肽（LY）的黏附片，以定位肽的递送并最大限度地减少胃中的稀释效应。方法：制备双层或三层黏合剂片，在处方层（LY/SNAC）的一侧或两侧涂覆海藻酸钠。在旋转圆筒上安装离体大鼠和小型猪胃组织，并在猴子体内进行黏附试验。该肽的口服生物利用度是通过口服黏合剂片在猴子体内测定的。结果：黏合剂在pH 6.8条件下15 min溶出bbb80 %。三层SNAC片粘附于离体胃组织。在给药后10-20分钟，猴子胃中保留10/10片黏合剂，而SNAC对照片为1/3。LY肽的口服生物利用度与SNAC对照片相似。黏附片的体内溶出速度比对照片慢，导致猴子胃内片区SNAC浓度较低。结论：这些数据表明粘粘片改善了胃潴留，但没有增加LY肽的口服生物利用度。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pharmaceutical Research 医学-化学综合

CiteScore

6.60

自引率

5.40%

发文量

276

审稿时长

3.4 months

期刊介绍： Pharmaceutical Research, an official journal of the American Association of Pharmaceutical Scientists, is committed to publishing novel research that is mechanism-based, hypothesis-driven and addresses significant issues in drug discovery, development and regulation. Current areas of interest include, but are not limited to: -(pre)formulation engineering and processing- computational biopharmaceutics- drug delivery and targeting- molecular biopharmaceutics and drug disposition (including cellular and molecular pharmacology)- pharmacokinetics, pharmacodynamics and pharmacogenetics. Research may involve nonclinical and clinical studies, and utilize both in vitro and in vivo approaches. Studies on small drug molecules, pharmaceutical solid materials (including biomaterials, polymers and nanoparticles) biotechnology products (including genes, peptides, proteins and vaccines), and genetically engineered cells are welcome.