Li Zhuo, Li Haiyan, Wang Caifen, Xu Jianghui, Singh Vikramjeet, Chen Dawei, Zhang Jiwen
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China; Center for Drug Delivery System, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Center for Drug Delivery System, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Acta Pharm Sin B. 2016 Jul;6(4):344-51. doi: 10.1016/j.apsb.2016.03.003. Epub 2016 Mar 26.
In an answer to the challenge of enzymatic instability and low oral bioavailability of proteins/peptides, a new type of drug-delivery vesicle has been developed. The preparation, based on sodium dodecyl sulfate (SDS) and β-cyclodextrin (β-CD) embedded in chitosan gel, was used to successfully deliver the model drug-insulin. The self-assembled SDS/β-CD vesicles were prepared and characterized by particle size, zeta potential, appearance, microscopic morphology and entrapment efficiency. In addition, both the interaction of insulin with vesicles and the stability of insulin loaded in vesicles in the presence of pepsin were investigated. The vesicles were crosslinked into thermo-sensitive chitosan/β-glycerol phosphate solution for an in-situ gel to enhance the dilution stability. The in vitro release characteristics of insulin from gels in media at different pH values were investigated. The insulin loaded vesicles-chitosan hydrogel (IVG) improved the dilution stability of the vesicles and provided pH-selective sustained release compared with insulin solution-chitosan hydrogel (ISG). In vitro, IVG exhibited slow release in acidic solution and relatively quick release in neutral solutions to provide drug efficacy. In simulated digestive fluid, IVG showed better sustained release and insulin protection properties compared with ISG. Thus IVG might improve the stability of insulin during its transport in vivo and contribute to the bioavailability and therapeutic effect of insulin.
为应对蛋白质/肽类药物酶不稳定性和口服生物利用度低的挑战，已开发出一种新型药物递送囊泡。该制剂基于嵌入壳聚糖凝胶中的十二烷基硫酸钠（SDS）和β-环糊精（β-CD），成功用于递送模型药物胰岛素。制备了自组装的SDS/β-CD囊泡，并通过粒径、zeta电位、外观、微观形态和包封率进行表征。此外，还研究了胰岛素与囊泡的相互作用以及在胃蛋白酶存在下负载于囊泡中的胰岛素的稳定性。将囊泡交联到热敏性壳聚糖/β-甘油磷酸溶液中形成原位凝胶，以提高稀释稳定性。研究了胰岛素在不同pH值介质中从凝胶的体外释放特性。与胰岛素溶液-壳聚糖水凝胶（ISG）相比，负载胰岛素的囊泡-壳聚糖水凝胶（IVG）提高了囊泡的稀释稳定性，并提供了pH选择性缓释。在体外，IVG在酸性溶液中表现出缓慢释放，在中性溶液中相对快速释放以发挥药效。在模拟消化液中，与ISG相比，IVG表现出更好的缓释和胰岛素保护性能。因此，IVG可能会提高胰岛素在体内转运过程中的稳定性，并有助于提高胰岛素的生物利用度和治疗效果。
