Ameliorating the antitumor activity of lenalidomide using PLGA nanoparticles for the treatment of multiple myeloma

Abstract Lenalidomide (LND) is an anti-cancer drug and an effective derivative of thalidomide used for multiple myeloma therapy. Because of its poor solubility in water, LND is known to cause low oral bioavailability (below 33%), and as a direct consequence of this, the dosing frequency is extended thus increasing risk of toxicity. To improve its bioavailability and sustained release, the present study aims to formulate polymeric nanoparticles (NPs) for LND using [Poly (lactic-co-glycolic acid)] (PLGA) as a polymer. The polymeric NPs were evaluated for particle size, SEM, XRD, drug content, entrapment efficiency (EE), in vitro release studies and in vivo bioavailability studies in rats. The formulated NPs possessed a size of 179±0.9 nm and a zeta potential of -24.4 ± 0.2 mV. The drug loading and EE of the optimized formulation was 32 ± 0.37 % and 78 ± 0.92% respectively. After oral administration of LND PLGA-NPs, the relative bioavailability was enhanced about 3.67-fold compared to LND. This study demonstrates the novel drug delivery for LND with PLGA-NPs as effective drug delivery system for sustained delivery of LND.

摘要 来那度胺（Lenalidomide，LND）是一种抗肿瘤药物，同时也是沙利度胺的有效衍生物，临床用于多发性骨髓瘤的治疗。由于其水溶性较差，来那度胺的口服生物利用度较低（低于33%），这直接导致给药频次增加，进而升高了毒性发生风险。为提升其生物利用度并实现持续释药，本研究以聚乳酸-羟基乙酸共聚物[Poly (lactic-co-glycolic acid)]（PLGA）为载体材料，制备了载来那度胺的聚合物纳米粒（NPs）。对所制备的聚合物纳米粒，我们开展了粒径表征、扫描电镜（SEM）分析、X射线衍射（XRD）检测、药物含量测定、包封率（EE）考察、体外释放试验以及大鼠体内生物利用度研究。结果显示，优化所得纳米粒的粒径为179±0.9 nm，ζ电位（zeta potential）为-24.4±0.2 mV；其载药量与包封率分别为32±0.37%与78±0.92%。与游离来那度胺原料药相比，口服给予来那度胺PLGA纳米粒制剂后，受试动物体内来那度胺的相对生物利用度提升约3.67倍。本研究证实，基于PLGA纳米粒的来那度胺新型给药系统可作为有效的缓释递送载体，实现来那度胺的持续给药。