School of Materials Science & Engineering, Nanyang Technological University, 639798 Singapore, Singapore.
Small. 2012 Aug 20;8(16):2585-94. doi: 10.1002/smll.201200398. Epub 2012 Jun 6.
Nanoparticles made from poly(dl-lactide-co-glycolide) (PLGA) are used to deliver a wide range of bioactive molecules, due to their biocompatibility and biodegradability. This study investigates the surface modification of PLGA nanoparticles via the layer-by-layer (LbL) deposition of polyelectrolytes, and the effects of these coatings on the release behavior, cytotoxicity, hemolytic activity, and cellular uptake efficiency. PLGA nanoparticles are modified via LbL adsorption of two polyelectrolyte pairs: 1) poly(allylamine hydrochloride) (PAH) and poly(styrene sulfonate) (PSS) and 2) poly(L-lysine hydrobromide) (PLL) and dextran sulfate (DES). It is demonstrated that both PAH/PSS and PLL/DES coatings suppress the burst release usually observed for unmodified PLGA nanoparticles and that the release behavior can be adjusted by changing the layer numbers, layer materials, or by crosslinking the layer constituents. Neither bare nor polyelectrolyte-modified PLGA nanoparticles show any signs of cytotoxicity. However, nanoparticles with a positively charged polyelectrolyte as the outermost layer induce hemolysis, whereas uncoated particles or particles with a negatively charged polyelectrolyte as the outermost layer show no hemolytic activity. Furthermore, particles with either PAH or PLL as the outermost layer also demonstrate a higher uptake efficiency by L929 fibroblast cells, due to a higher cell-particle affinity. This study suggests that LbL coating of PLGA nanoparticles can control the release behavior of bioactive molecules as well as the surface activity, therefore providing a promising strategy to enhance the efficiency of nanoparticulate drug-delivery systems.
聚（丙交酯-共-乙交酯）（PLGA）纳米颗粒由于其生物相容性和可生物降解性，被用于递送各种生物活性分子。本研究通过层层（LbL）沉积聚电解质来研究 PLGA 纳米颗粒的表面改性，以及这些涂层对释放行为、细胞毒性、溶血活性和细胞摄取效率的影响。通过 LbL 吸附两种聚电解质对 PLGA 纳米颗粒进行改性：1）聚烯丙基胺盐酸盐（PAH）和聚苯乙烯磺酸盐（PSS）和 2）聚（L-赖氨酸氢溴酸盐）（PLL）和葡聚糖硫酸盐（DES）。结果表明，PAH/PSS 和 PLL/DES 涂层均能抑制未改性 PLGA 纳米颗粒通常观察到的突释，并且可以通过改变层数量、层材料或交联层成分来调节释放行为。无论是裸纳米颗粒还是聚电解质修饰的纳米颗粒都没有表现出任何细胞毒性的迹象。然而，带正电荷的聚电解质作为最外层的纳米颗粒会引起溶血，而不带电或带负电荷的聚电解质作为最外层的纳米颗粒则没有溶血活性。此外，带 PAH 或 PLL 作为最外层的颗粒也表现出更高的由 L929 成纤维细胞摄取的效率，这是由于更高的细胞-颗粒亲和力。本研究表明，LbL 涂层可以控制生物活性分子的释放行为以及表面活性，从而为提高纳米粒药物传递系统的效率提供了一种有前途的策略。
