期刊
BIOMATERIALS
卷 35, 期 25, 页码 7172-7179出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2014.04.104
关键词
Porous silicon; Insulin; Diabetes; Chitosan; Cell monolayers; Microparticles
资金
- Finnish Center for International Mobility, CIMO [TM-12-8434]
- Fundacao para a Ciencia e a Tecnologia (FCT) [SFRH/BD/87016/2012]
- Academy of Finland [252215]
- University of Helsinki Research Funds
- Fundação para a Ciência e a Tecnologia [SFRH/BD/87016/2012] Funding Source: FCT
Porous silicon (PSi) based particulate systems are emerging as an important drug delivery system due to its advantageous properties such as biocompatibility, biodegradability and ability to tailor the particles' physicochemical properties. Here, annealed thermally hydrocarbonized PSi (AnnTHCPSi) and undecylenic acid modified AnnTHCPSi (AnnUnTHCPSi) microparticles were developed as a PSi-based platform for oral delivery of insulin. Chitosan (CS) was used to modify the AnnUnTHCPSi microparticles to enhance the intestinal permeation of insulin. Surface modification with CS led to significant increase in the interaction of PSi microparticles with Caco-2/HT-29 cell co-culture monolayers. Compared to pure insulin, the CS-conjugated microparticles significantly improved the permeation of insulin across the Caco2/HT-29 cell monolayers, with ca. 20-fold increase in the amount of insulin permeated and ca. 7-fold increase in the apparent permeability (P-app) value. Moreover, among all the investigated particles, the CS-conjugated microparticles also showed the highest amount of insulin associated with the mucus layer and the intestinal Caco-2 cells and mucus secreting HT-29 cells. Our results demonstrate that CSconjugated AnnUnTHCPSi microparticles can efficiently enhance the insulin absorption across intestinal cells, and thus, they are promising microsystems for the oral delivery of proteins and peptides across the intestinal cell membrane. (C) 2014 Elsevier Ltd. All rights reserved.
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