Department of Surgery, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia.
Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia.
Life Sci. 2019 Mar 1;220:136-146. doi: 10.1016/j.lfs.2019.01.053. Epub 2019 Jan 31.
This study aims to develop and evaluate oleuropein loaded surface functionalized folate-targeted - PEG liposomes for the effective management of prostate cancer in an animal model.
Film hydration-cum-extrusion technique was used to produce liposomes. Particle size, entrapment efficiency, drug loading, electron microscopy, and drug release study were performed for the characterization. Cell viability and various in vitro studies (phosphatidylserine internalization, TUNEL assay, measurement of mitochondrial membrane potential and caspase-3 assay) were performed to compare the anticancer and apoptotic effects of developed liposomes against the plain oleuropein. Comparative pharmacokinetic profiling and anticancer efficacy studies including a change in tumor volume, body weight, and survival analysis were performed in mice model.
The developed liposomes (OL-FML) showed the particle size of 184.2 ± 9.16 nm, the zeta potential of 1.41 ± 0.24 mV, entrapment efficiency of 63.52 ± 4.15% and drug loading of 21.31 ± 2.37%. OL-FML showed higher in vitro anti-proliferative effect and apoptosis on 22Rv1 cells. In vivo pharmacokinetic study revealed a nearly 6 fold increase in the bioavailability of OL-FML (AUC = 641.78 ± 103.764 μg/mL·hr) as compared to OL solution (AUC = 104.11 ± 18.374 μg/mL·hr) in mice. Increased tumor suppression, weight loss resistance, and survival probability were observed in 22Rv1 induced tumor-bearing mice with OL-FML treatment as compared to OL.
The study provides conclusive evidence for the utilization of combining passive and active targeting strategy to enhance the anticancer effect of OL.
本研究旨在开发并评估橄榄苦苷负载的表面功能化叶酸靶向-PEG 脂质体，以在动物模型中有效治疗前列腺癌。
采用薄膜水化-挤出技术制备脂质体。进行粒径、包封率、载药量、电子显微镜和药物释放研究以进行表征。进行细胞活力和各种体外研究（磷脂酰丝氨酸内化、TUNEL 测定、线粒体膜电位测定和 caspase-3 测定），以比较开发的脂质体与普通橄榄苦苷的抗癌和促凋亡作用。在小鼠模型中进行比较药代动力学特征分析和抗癌疗效研究，包括肿瘤体积变化、体重变化和生存分析。
所开发的脂质体（OL-FML）的粒径为 184.2±9.16nm，zeta 电位为 1.41±0.24mV，包封率为 63.52±4.15%，载药量为 21.31±2.37%。OL-FML 在 22Rv1 细胞上显示出更高的体外增殖抑制作用和凋亡作用。体内药代动力学研究表明，与 OL 溶液（AUC=104.11±18.374μg/mL·hr）相比，OL-FML 的生物利用度增加了近 6 倍（AUC=641.78±103.764μg/mL·hr）。与 OL 相比，OL-FML 治疗 22Rv1 诱导的荷瘤小鼠的肿瘤抑制、体重减轻抵抗和生存概率均增加。
该研究为结合被动和主动靶向策略来增强 OL 的抗癌作用提供了确凿的证据。
