Pin Pin Ma, Zi Ling Li, Hong Xia Gao, Xiang Yuan Xiong
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引用次数: 0
Abstract
The intestinal epithelium barrier is one of the main factors limiting the bioavailability of oral insulin delivery systems. Neonatal Fc (fragment crystallizable) receptor (FcRn) is highly expressed in the intestinal epithelium, which can bind specifically to the Fc fragments of IgG in a pH-dependent manner and thus improve the transepithelial transport of carriers modified by IgG Fc or Fc domain-binding peptides (FcBP) ligand. Thus, FcBP ligand was attached to Pluronic F127-polylactic acid polymersomes by using the biotin-avidin bridging technology to obtain FcRn-targeted FcBP-F127-PLA polymersomes. Insulin (INS) was loaded successfully into FcBP-F127-PLA with the loading efficiency of 12.01 %. The transepithelial transport experiments on Caco-2 cells using Coumarin-6 (C-6) as a fluorescence probe showed that the cumulative permeability percentage and apparent permeability coefficient (Papp) of the FcBP-F127-PLA/C-6 group was 1.7 and 1.8 times that of PLA-F127-PLA/C-6 group after 2 h of incubation, respectively. FcBP ligand density of FcBP-F127-PLA played a role on their transepithelial transport ability and 10%FcBP-F127-PLA with 10 % FcBP molar content was found to be the best. The in vivo hypoglycemic results showed that the relative pharmacological bioavailability (PAR%) of the oral 10%FcBP-F127-PLA/INS group was 43.6 %, which was 1.27 times that of the PLA-F127-PLA/INS group. Therefore, FcBP-F127-PLA polymersomes could be a promising carrier of the oral insulin delivery.
期刊介绍:
The European Journal of Pharmaceutics and Biopharmaceutics provides a medium for the publication of novel, innovative and hypothesis-driven research from the areas of Pharmaceutics and Biopharmaceutics.
Topics covered include for example:
Design and development of drug delivery systems for pharmaceuticals and biopharmaceuticals (small molecules, proteins, nucleic acids)
Aspects of manufacturing process design
Biomedical aspects of drug product design
Strategies and formulations for controlled drug transport across biological barriers
Physicochemical aspects of drug product development
Novel excipients for drug product design
Drug delivery and controlled release systems for systemic and local applications
Nanomaterials for therapeutic and diagnostic purposes
Advanced therapy medicinal products
Medical devices supporting a distinct pharmacological effect.