4.4 Article

β-Cyclodextrin-containing chitosan-oligonucleotide nanoparticles improve insulin bioactivity, gut cellular permeation and glucose consumption

期刊

JOURNAL OF PHARMACY AND PHARMACOLOGY
卷 73, 期 6, 页码 726-739

出版社

OXFORD UNIV PRESS
DOI: 10.1093/jpp/rgaa052

关键词

insulin; lyophilisation; nanoparticle; oral

资金

  1. Australian Government through Australian Government Research Training Program Scholarship
  2. European Union [872370]

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In this study, a nanoparticulate drug delivery system was developed to protect insulin in the GI tract. The addition of cryoprotectants improved stability, encapsulation efficiency, and reduced premature release of insulin. The entrapped insulin maintained bioactivity in enzymatic medium.
Objectives The main objective of the present study was to develop a nanoparticulate drug delivery system that can protect insulin against harsh conditions in the gastrointestinal (GI) tract. The effects of the following employed techniques, including lyophilisation, cross-linking and nanoencapsulation, on the physicochemical properties of the formulation were investigated. Methods We herein developed a nanocarrier via ionotropic gelation by using positively charged chitosan and negatively charged Dz13Scr. The lyophilised nanoparticles with optimal concentrations of tripolyphosphate (cross-linking agent) and beta-cyclodextrin (stabilising agent) were characterised by using physical and cellular assays. Key findingsThe addition of cryoprotectants (1% sucrose) in lyophilisation improved the stability of nanoparticles, enhanced the encapsulation efficiency, and ameliorated the pre-mature release of insulin at acidic pH. The developed lyophilised nanoparticles did not display any cytotoxic effects in C2C12 and HT-29 cells. Glucose consumption assays showed that the bioactivity of entrapped insulin was maintained post-incubation in the enzymatic medium. Conclusions Freeze-drying with appropriate cryoprotectant could conserve the physiochemical properties of the nanoparticles. The bioactivity of the entrapped insulin was maintained. The prepared nanoparticles could facilitate the permeation of insulin across the GI cell line.

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