Liu James, Boonkaew Benjawan, Arora Jaspreet, Mandava Sree Harsha, Maddox Michael M, Chava Srinivas, Callaghan Cameron, He Jibao, Dash Srikanta, John Vijay T, Lee Benjamin R
Department of Urology, Tulane University School of Medicine, New Orleans, Louisiana.
J Pharm Sci. 2015 Mar;104(3):1187-96. doi: 10.1002/jps.24318. Epub 2015 Jan 8.
The objective of this study is to develop and compare several Sorafenib-loaded biocompatible nanoparticle models in order to optimize drug delivery and tumor cellular kill thereby improving the quality of Sorafenib-regimented chemotherapy. Sorafenib-loaded poly (lactic-co-glycolic) acid (PLGA), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) liposomes, and hydrophobically modified chitosan (HMC)-coated DPPC liposomes were evaluated for several characteristics including zeta potential, drug loading, and release profile. Cytotoxicity and uptake trials were also studied using cell line RCC 786-0, a human metastatic clear cell histology renal cell carcinoma cell line. Sorafenib-loaded PLGA particles and HMC-coated DPPC liposomes exhibited significantly improved cell kill compared to Sorafenib alone at lower concentrations, namely 10-15 and 5-15 μM from 24 to 96 h, respectively. At maximum dosage and time (15 μM and 96 h), Sorafenib-loaded PLGA and HMC-coated liposomes killed 88.3 ± 1.8% and 98 ± 1.1% of all tumor cells, significant values compared with Sorafenib 81.8 ± 1.7% (p < 0.01). Likewise, HMC coating substantially improved cell kill for liposome model for all concentrations (5-15 μM) and at time points (24-96 h) (p < 0.01). PLGA and HMC-coated liposomes are promising platforms for drug delivery of Sorafenib. Because of different particle characteristics of PLGA and liposomes, each model can be further developed for unique clinical modalities.
本研究的目的是开发并比较几种载有索拉非尼的生物相容性纳米颗粒模型,以优化药物递送和肿瘤细胞杀伤,从而提高索拉非尼化疗方案的质量。对载有索拉非尼的聚乳酸 - 乙醇酸共聚物(PLGA)、1,2 - 二棕榈酰 - sn - 甘油 - 3 - 磷酸胆碱(DPPC)脂质体以及疏水改性壳聚糖(HMC)包被的DPPC脂质体进行了多项特性评估,包括zeta电位、药物负载量和释放曲线。还使用人转移性透明细胞组织学肾癌细胞系RCC 786 - 0进行了细胞毒性和摄取试验。与单独使用索拉非尼相比,载有索拉非尼的PLGA颗粒和HMC包被的DPPC脂质体在较低浓度下(分别为10 - 15 μM和5 - 15 μM,作用时间为24至96小时)表现出显著改善的细胞杀伤效果。在最大剂量和时间(15 μM和96小时)时,载有索拉非尼的PLGA和HMC包被的脂质体分别杀死了88.3 ± 1.8%和98 ± 1.1%的所有肿瘤细胞,与索拉非尼的81.8 ± 1.7%相比具有显著差异(p < 0.01)。同样,对于所有浓度(5 - 15 μM)和时间点(24 - 96小时),HMC包被显著改善了脂质体模型的细胞杀伤效果(p < 0.01)。PLGA和HMC包被的脂质体是索拉非尼药物递送的有前景的平台。由于PLGA和脂质体具有不同的颗粒特性,每个模型都可以针对独特的临床模式进行进一步开发。