姜黄素类似物CA7脂质体的研发及其体外和体内抗宫颈癌疗效评估

Development of the Curcumin Analog CA7 Liposome and Its Evaluation for Efficacy Against Cervical Cancer in vitro and in vivo.

作者信息

Xiong Linjin, Wei Yumeng, Si Hui, Li Zheng, Wen Jie, Liu Furong, Wang Xiaodong, Yang Hongru, Chen Ligang, Pi Chao, Han Yunwei, Zhao Ling

机构信息

Key Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy of Southwest Medical University, Luzhou, 646000, People's Republic of China.

Department of Psychiatry, Fundamental and Clinical Research on Mental Disorders Key Laboratory of Luzhou, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan, 646000, People's Republic of China.

出版信息

Int J Nanomedicine. 2024 Dec 13;19:13411-13428. doi: 10.2147/IJN.S493074. eCollection 2024.

DOI:10.2147/IJN.S493074

PMID:39691454

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11651071/

Abstract

OBJECTIVE

The objective of this study was to develop liposomes (LP) containing a curcumin (CU) analog CA7 to enhance its pharmacokinetic profile and anti-cervical cancer (CC) effects.

METHODS

Single-factor and Box-Behnken experiments were conducted to optimize the formulation of CA7-loaded liposomes (CA7-LP). The in vitro release, stability, biocompatibility, and pharmacokinetic of CA7-LP were evaluated. The biological effects of CA7-LP on Hela cells were assessed using MTT assays, colony formation assays, wound healing assays, and flow cytometry. Additionally, the anti-CC efficacy of CA7-LP was tested in mouse models of transplanted tumors.

RESULTS

The optimal formulation of CA7-LP exhibited a particle size of 92.43 ± 1.52 nm, a polydispersity index of 0.27 ± 0.01, an encapsulation efficiency of 97.79 ± 1.49%, a drug loading of 3.23 ± 0.20%, and a zeta potential of -6.69 ± 0.77 mV. Transmission electron microscopy confirmed that a spherical morphology was exhibited by CA7-LP. The cumulative in vitro release of CA7-LP was found to be 2.84 times greater than that of CA7, and stability at room temperature was maintained for at least 90 d. Furthermore, a significantly higher uptake of CA7-LP by Hela cells was observed compared to curcumin and CA7, leading to enhanced inhibition of cell proliferation, migration and cell cycle, as well as increased apoptosis ( < 0.05). In vivo studies revealed that CA7-LP exhibited superior pharmacokinetic properties compared to CA7 (AUC: 3.58-fold, C: 5.65-fold, t: 1.2-fold). The anti-CC effects of CA7-LP were found to be comparable to those of Cisplatin injection, with a better safety profile.

CONCLUSION

The newly developed CA7-LP is considered a promising candidate for the treatment of CC, demonstrating high potential for clinical application.

摘要

目的

本研究的目的是开发含有姜黄素（CU）类似物CA7的脂质体（LP），以改善其药代动力学特征和抗宫颈癌（CC）效果。

方法

进行单因素和Box-Behnken实验以优化载CA7脂质体（CA7-LP）的配方。评估了CA7-LP的体外释放、稳定性、生物相容性和药代动力学。使用MTT法、集落形成法、伤口愈合法和流式细胞术评估CA7-LP对Hela细胞的生物学效应。此外，在移植瘤小鼠模型中测试了CA7-LP的抗CC疗效。

结果

CA7-LP的最佳配方显示粒径为92.43±1.52nm，多分散指数为0.27±0.01，包封率为97.79±1.49%，载药量为3.23±0.20%，ζ电位为-6.69±0.77mV。透射电子显微镜证实CA7-LP呈现球形形态。发现CA7-LP的体外累积释放量比CA7高2.84倍，并且在室温下的稳定性至少维持90天。此外，与姜黄素和CA7相比，观察到Hela细胞对CA7-LP的摄取明显更高，导致对细胞增殖、迁移和细胞周期的抑制增强，以及细胞凋亡增加（P<0.05）。体内研究表明，与CA7相比，CA7-LP表现出更好的药代动力学性质（AUC：3.58倍，Cmax：5.65倍，t1/2：1.2倍）。发现CA7-LP的抗CC效果与顺铂注射液相当，且安全性更好。