Utilization of PLGA nanoparticles in yeast cell wall particle system for oral targeted delivery of exenatide to improve its hypoglycemic efficacy

PLGA公司 生物物理学 化学 内吞作用 纳米颗粒 控制释放 药物输送 体内 艾塞那肽 材料科学 药理学 生物医学工程 纳米技术 细胞 生物化学 医学 糖尿病 内分泌学 生物 生物技术 2型糖尿病
作者
Tianyang Ren,Xuehua Zheng,Ruixue Bai,Yongrong Yang,Lingyan Jian
出处
期刊:International Journal of Pharmaceutics [Elsevier]
卷期号:601: 120583-120583 被引量:18
标识
DOI:10.1016/j.ijpharm.2021.120583
摘要

Oral delivery of exenatide (EXE), a high-efficiency therapeutic peptide, is urgently needed for long-term treatment of diabetes. In this study, a polylactide-co-glycoside (PLGA) nanoparticles (NPs) in yeast cell wall particle (YCWP) system was built to improve the intestinal absorption of EXE by efficient protection of EXE against gastrointestinal degradation and intestinal phagocytic cell targeted delivery. The EXE-loaded PLGA NPs were prepared by a double emulsion solvent diffusion method and exhibited a uniformly spherical appearance, a nano size (92.4 ± 4.6 nm) and a positive surface charge (+32.3 ± 3.8 mV). And then, the NPs were successfully loaded into the YCWPs by a solvent hydration - lyophilization cycle method to obtain the EXE-PLGA NPs @YCWPs, which was verified by scanning electron microscope and confocal laser scanning microscopy. An obvious sustained drug release and a reduced burst release were achieved by this nano-in-micro carrier. Moreover, the gastrointestinal stability of EXE in PLGA NPs @YCWPs was significantly higher than that in PLGA NPs in the simulated gastrointestinal environment, which were useful in enhancing the intestinal absorption of EXE. In biodistribution study, the EXE-PLGA NPs @YCWPs could quickly reached the root of the villi, and even partly entered the inner of the villi, especially in ileum and Peyer's patches. In vitro cell evaluation demonstrated an efficient β-glucan receptor mediated endocytosis and transport of EXE-PLGA NPs @YCWPs by the macrophage RAW 264.7 cells, suggesting a potential intestinal macrophage targeted absorptive pathway. The in vivo pharmacokinetic study showed a preferred hypoglycemic effect and an increased pharmacological availability (13.7 ± 4.1%) after oral administration of the EXE-PLGA NPs @YCWPs. It is believed that the PLGA nanoparticles in YCWP system could become an efficient strategy to orally deliver therapeutic peptide drugs.
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