Department of Pharmaceutical Sciences, University of Modena and Reggio Emilia, Via Campi 183, Modena, Italy.
Eur J Pharm Sci. 2010 Oct 9;41(2):254-64. doi: 10.1016/j.ejps.2010.06.012. Epub 2010 Jul 1.
Cidofovir (HPMPC) was recently reported to exert a valuable antineoplastic activity against primary effusion lymphoma (PEL), a B-cell neoplasm associated with Human Herpesvirus-8 (HHV-8) infection. In this study, we developed and characterized liposomes encapsulating HPMPC to increase drug efficacy reducing the administered dose and the related toxicity, which actually hamper its clinical therapeutic use in patients affected with PEL. The liposomes, obtained using different formulations of neutral and cationic lipids, were analyzed by microscopical (AFM) and spectroscopical (PCS and NMR) techniques. Using an in vitro model of PEL (BCBL-1 cell line), the carrier toxicity and the antineoplastic efficacy of liposomes were evaluated by flow cytometry applying apoptosis and cell death analysis. The in vitro study showed the applicability of the liposomes within a restricted range of lipidic concentrations according to the lipids used during the preparation. The moderate increases in the percentage of apoptotic/necrotic cells suggests that liposomal delivery allows the release of HPMPC into BCBL-1 cells enabling an unexpected antineoplastic activity of this drug even at lower doses.
西多福韦(HPMPC)最近被报道具有针对原发性渗出性淋巴瘤(PEL)的有价值的抗肿瘤活性,PEL 是一种与人类疱疹病毒 8 型(HHV-8)感染相关的 B 细胞肿瘤。在这项研究中,我们开发并表征了包封 HPMPC 的脂质体,以提高药物功效,减少给药剂量和相关毒性,这实际上阻碍了其在患有 PEL 的患者中的临床治疗用途。使用中性和阳离子脂质的不同配方获得的脂质体通过显微镜(AFM)和光谱(PCS 和 NMR)技术进行分析。使用 PEL 的体外模型(BCBL-1 细胞系),通过应用凋亡和细胞死亡分析的流式细胞术评估脂质体的载体毒性和抗肿瘤功效。体外研究表明,根据制备过程中使用的脂质,脂质体在脂质浓度的有限范围内具有适用性。凋亡/坏死细胞百分比的适度增加表明,脂质体递送允许 HPMPC 释放到 BCBL-1 细胞中,使该药物即使在较低剂量下也能发挥出意想不到的抗肿瘤活性。