School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
Int J Pharm. 2019 Jan 10;554:36-47. doi: 10.1016/j.ijpharm.2018.10.068. Epub 2018 Oct 29.
It is desirable to design nanoparticles for oral insulin delivery that can cross mucus layer and epithelial membrane in the intestine in the meantime. Thus, using chitosan (CS) as the nanocarrier, the objective of this study is to elucidate the contribution of surface hydrophilic and hydrophobic modification on the oral absorption of insulin and the essential for these two strategies combination. First of all, the polyelectronic nanocomplexes (PEC) based on synthesized CS-g-polyethylene glycol monomethyl ether (mPEG) copolymers with different mPEG graft ratios were prepared by self-assembly method and their physicochemical properties were characterized, and surface hydrophilicity and interaction with mucus were estimated. The hypoglycemic effect and pharmacological availability of the PECs following oral administration were evaluated in rats. It was found that the best absorption was achieved at mPEG graft ratio 10%. Thereafter, with newly synthesized mPEG-CS-glyceryl monocaprylate (GMC) copolymers, the added hydrophobic modification on the in vitro and in vivo properties of the mPEG-CS based PECs were explored. Further modification of CS-mPEG with GMC led to prolonged therapeutic effect but without statistical difference in pharmacological availability. In summary, this study indicated that the in vivo absorption of nanocarrier was surface property dependent, with appropriate hydrophilicity preferred over hydrophobic modification.
理想情况下，设计用于口服胰岛素传递的纳米颗粒，使其能够同时穿过肠道中的黏液层和上皮细胞膜。因此，本研究使用壳聚糖（CS）作为纳米载体，旨在阐明表面亲水性和疏水性修饰对胰岛素口服吸收的贡献，以及这两种策略结合的必要性。首先，通过自组装方法制备了基于合成的 CS-g-聚乙二醇单甲醚（mPEG）共聚物的聚电解质纳米复合物（PEC），并对其理化性质进行了表征，同时评估了其表面亲水性和与黏液的相互作用。在大鼠中评估了 PEC 经口服给药后的降血糖作用和药代动力学可用性。结果发现，在 mPEG 接枝比为 10%时，吸收效果最佳。此后，使用新合成的 mPEG-CS-甘油单辛酸酯（GMC）共聚物，探索了 mPEG-CS 基 PEC 的体外和体内性质的附加疏水性修饰。CS-mPEG 与 GMC 的进一步修饰导致治疗效果延长，但药代动力学可用性没有统计学差异。总之，本研究表明，纳米载体的体内吸收取决于表面性质，适当的亲水性优于疏水性修饰。
