一种新型亚微米乳液系统，负载长春新碱-油酸离子对复合物，具有改善的抗癌效果：体外和体内研究。

A novel submicron emulsion system loaded with vincristine-oleic acid ion-pair complex with improved anticancer effect: in vitro and in vivo studies.

机构信息

Key Laboratory of Drug Targeting and Drug Delivery Systems, Sichuan University, Chengdu, People's Republic of China.

出版信息

Int J Nanomedicine. 2013;8:1185-96. doi: 10.2147/IJN.S41775. Epub 2013 Mar 20.

BACKGROUND

Vincristine (VCR), which is a widely used antineoplastic drug, was integrated with a submicron-emulsion drug-delivery system to enhance the anticancer effect.

METHODS

After the formation of a VCR-oleic acid ion-pair complex (VCR-OA), the VCR-OA-loaded submicron emulsion (VCR-OA-SME), prepared by classical high-pressure homogenization, was characterized and its in vitro anticancer effects were evaluated.

RESULTS

The submicron-emulsion formulation exhibited a homogeneous round shape. The mean particle size, zeta potential, and encapsulation efficiency were 157.6 ± 12.6 nm, -26.5 ± 5.0 mV and 78.64% ± 3.44%, respectively. An in vitro release study of the VCR-OA-SME revealed that 12.4% of the VCR was released within the first 2 hours (initial burst-release phase) and the rest of the drug was detected in the subsequent sustained-release phase. Compared with VCR solution, the pharmacokinetic study of VCR-OA-SME showed relatively longer mean residence time (mean residence time [0-∞] increased from 187.19 to 227.56 minutes), higher maximum concentration (from 252.13 ng/mL to 533.34 ng/mL), and greater area under the curve (area under the curve [0-∞] from 11,417.77 μg/L/minute to 17,164.34 μg/L/minute. Moreover, the VCR-OA-SME exhibited higher cytotoxicity (P < 0.05) on tumor cells by inducing cell arrest in the G2/M phase or even apoptosis (P < 0.05).

CONCLUSION

The VCR-OA-SME formulation in our study displayed great potential for an anticancer effect for VCR.

背景

长春新碱（VCR）是一种广泛应用的抗肿瘤药物，它与亚微米乳液药物递送系统结合使用，以增强抗癌效果。

方法

在形成长春新碱-油酸离子对复合物（VCR-OA）后，通过经典的高压匀质法制备长春新碱-OA 负载的亚微米乳剂（VCR-OA-SME），并对其进行表征和体外抗癌效果评估。

结果

亚微米乳剂制剂呈均匀的圆形。平均粒径、Zeta 电位和包封效率分别为 157.6±12.6nm、-26.5±5.0mV 和 78.64%±3.44%。VCR-OA-SME 的体外释放研究表明，12.4%的 VCR 在最初的 2 小时内释放（初始突释阶段），其余药物则在随后的持续释放阶段被检测到。与 VCR 溶液相比，VCR-OA-SME 的药代动力学研究显示相对较长的平均驻留时间（平均驻留时间[0-∞]从 187.19 分钟增加到 227.56 分钟）、更高的最大浓度（从 252.13ng/mL 增加到 533.34ng/mL）和更大的曲线下面积（曲线下面积[0-∞]从 11417.77μg/L/min 增加到 17164.34μg/L/min）。此外，VCR-OA-SME 通过诱导细胞在 G2/M 期停滞甚至凋亡，对肿瘤细胞表现出更高的细胞毒性（P<0.05）。