摘要
在口服给药中，纳米递药系统在增加药物胃肠道稳定性、提高药物口服生物利用度等多方面具备优良潜力，而纳米递药系统穿越肠道黏液层和上皮屏障的能力与其粒径、电荷、形状等性质息息相关。聚乳酸-羟基乙酸共聚物（Poly(lactic-co-glycolic acid)，PLGA）纳米粒在口服给药中研究广泛，为探究不同大小、电荷、形状的PLGA纳米粒穿越肠道屏障的能力，本研究采用乳化溶剂蒸发法、薄膜拉伸法制备上述不同性质的PLGA纳米粒，对其粒径、电位、形态、贮存稳定性、荧光泄漏进行了验证，并在体外水平比较了不同PLGA纳米粒穿越模拟黏液层的能力及在Caco-2细胞中的摄取能力。所制备的PLGA纳米粒具有预期制剂学性质，且贮存稳定性良好、在模拟黏液中无明显荧光泄漏，其穿越黏液层的程度及肠上皮细胞的摄取能力均与上述性质有较直接的关系。粒径、电荷、形状等性质是纳米粒设计中的重要参数，相关研究有望对口服纳米粒的合理设计提供信息。
关键词： 口服给药；PLGA纳米粒；粒径；电荷；形状
Abstract
In oral drug administration, nano drug delivery systems possess excellent potential in various aspects including promoting drug stability and improving oral bioavailability. The ability of nano-drug delivery systems to penetrate oral absorption barrier is closely related to their size, charge, shape, and relevant properties. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles have been extensively studied in oral drug delivery. To explore the influence of sizes, charges, and shapes of PLGA nanoparticle on their ability to cross the intestinal barrier, emulsion solvent evaporation and film-stretching methods were employed to prepare PLGA nanoparticles with the aforementioned properties. Their particle size, zeta potential, morphology, storage stability, and fluorescence leakage in simulated mucus were verified, and their ability to cross simulated mucus layer and their cellular uptake capacity in Caco-2 cells were evaluated in vitro. The PLGA nanoparticles exhibited the aforementioned different properties, along with good storage stability and negligible fluorescence leakage. The ability to cross the mucus layer and the cellular uptake capacity are directly related to these properties. Size, charge, and shape are important parameters in the design of nanoparticles, and relevant research could provide information for the rational design of oral nanoparticles.
Key words： Oral administration; PLGA nanoparticles; Particle size; Electric charge; Shape
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