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Liposomes containing glycocholate as potential oral insulin delivery systems: preparation, in vitro characterization, and improved protection against enzymatic degradation
Original Research
(1563) Views (755) Full article downloads
Authors: Niu M, Lu Y, Hovgaard L, Wu W
Published Date June 2011
Volume 2011:6 Pages 1155 - 1166
DOI: http://dx.doi.org/10.2147/IJN.S19917
Mengmeng Niu1, Yi Lu1, Lars Hovgaard2, Wei Wu11School of Pharmacy, Fudan University, Shanghai, People's Republic of China; 2Oral Formulation Development, Novo Nordisk A/S, Maalov, Denmark
Background: Oral delivery of insulin is challenging and must overcome the barriers of gastric and enzymatic degradation as well as low permeation across the intestinal epithelium. The present study aimed to develop a liposomal delivery system containing glycocholate as an enzyme inhibitor and permeation enhancer for oral insulin delivery.
Methods: Liposomes containing sodium glycocholate were prepared by a reversed-phase evaporation method followed by homogenization. The particle size and entrapment efficiency of recombinant human insulin (rhINS)-loaded sodium glycocholate liposomes can be easily adjusted by tuning the homogenization parameters, phospholipid:sodium glycocholate ratio, insulin:phospholipid ratio, water:ether volume ratio, interior water phase pH, and the hydration buffer pH.
Results: The optimal formulation showed an insulin entrapment efficiency of 30% ± 2% and a particle size of 154 ± 18 nm. A conformational study by circular dichroism spectroscopy and a bioactivity study confirmed the preserved integrity of rhINS against preparative stress. Transmission electron micrographs revealed a nearly spherical and deformed structure with discernable lamella for sodium glycocholate liposomes. Sodium glycocholate liposomes showed better protection of insulin against enzymatic degradation by pepsin, trypsin, and a-chymotrypsin than liposomes containing the bile salt counterparts of sodium taurocholate and sodium deoxycholate.
Conclusion: Sodium glycocholate liposomes showed promising in vitro characteristics and have the potential to be able to deliver insulin orally.
Keywords: liposomes, glycocholate, insulin, enzymatic degradation, oral
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