Issue 5, 2021

A novel cyanoacrylate-based matrix excipient in HPMCP capsules forms a sustained intestinal delivery system for orally administered drugs with enhanced absorption efficiency

Abstract

Patients prefer oral drug delivery due to its convenience and noninvasiveness. Nevertheless, a multitude of potentially clinically important drugs will not reach the market or achieve their full potential, due to their low bioavailability and instability in gastric acid. In this study, a novel oral drug delivery system based on poly-cyanoacrylate [a polymer of 2-(2-methoxyethoxy)ethyl-2-cyanoacrylate (MECA)] and hydroxypropyl methylcellulose phthalate (HPMCP) was developed and shown to permit intestinal targeting and sustained drug release. Aspirin [acetylsalicylic acid (ASA)] was selected as a model drug for atherosclerosis treatment. It was physically dissolved in liquid MECA, and the ASA–MECA matrix was then polymerized into a solid drug-loading depot in an HPMCP shell. The delivery of the drug depot in the intestine was achieved with the HPMCP shell; then the polymerized MECA (polyMECA) provided sustained drug release. The polyMECA excipient was not absorbed by the intestine due to its high molecular weight; a fluorescein-labeled assay indicated that it was excreted completely in feces after drug release. The formulation, ASA–polyMECA–HPMCP, showed good intestinal targeting and sustained drug release in vitro and in vivo. Pharmacokinetic studies indicated that this formulation improved the bioavailability of ASA relative to commercially available controls. ASA–polyMECA–HPMCP showed desirable anti-atherosclerosis efficacy in a rabbit model, with significant enhancement of atheromatous lesion stability. Biosafety tests proved the low toxicity of ASA–polyMECA–HPMCP and the polyMECA matrix. We believe that this work has provided a practical and biocompatible system for sustained intestinal drug delivery that can be applied broadly with various drugs for specific therapeutic aims.

Graphical abstract: A novel cyanoacrylate-based matrix excipient in HPMCP capsules forms a sustained intestinal delivery system for orally administered drugs with enhanced absorption efficiency

Supplementary files

Article information

Article type
Paper
Submitted
04 Nov 2020
Accepted
22 Dec 2020
First published
22 Dec 2020

J. Mater. Chem. B, 2021,9, 1288-1296

A novel cyanoacrylate-based matrix excipient in HPMCP capsules forms a sustained intestinal delivery system for orally administered drugs with enhanced absorption efficiency

L. Song, P. Chen, J. Yu, X. Han, Y. Hua, S. Liu, B. Pang, J. Gao, J. Ma and L. Xu, J. Mater. Chem. B, 2021, 9, 1288 DOI: 10.1039/D0TB02606A

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