Department of Cardiovascular Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650101, China.
Acta Biochim Pol. 2020 Jun 8;67(2):149-155. doi: 10.18388/abp.2020_5142.
The present investigation aimed at developing Doxorubicin (DOX)-loaded liposome-mediated drug delivery system for head and neck cancer. The liposomes were prepared by film hydration technique using egg phosphatidylcholine and cholesterol using Box-Behnken statistical design. The prepared liposomes were evaluated for the percentage encapsulation efficiency, particle size and in vitro release. The average particle size of the DOX-encapsulating liposomes formulated by thin-film hydration technique was between 150.5 nm and 200 nm with an average particle size of 165.80 nm. The PDI (Polydispersity index) was found to be 0.315 which indicated that particles were monodispersed and narrow-dispersed. In vitro drug release of DOX-loaded liposomes and DOX-loaded peptide-conjugated liposomes was performed in phosphate buffered saline (pH 7.4) and both formulations showed sustained release behavior over the period of 40 hours. The optimized liposomal formulation was conjugated to a peptide and subsequently radiolabeled with 186Re-perrhenate solution and BMEDA-glucoheptonate-stannous chloride solution. Comparative cytotoxicity assay of DOX, DOX-liposomes and DOX-liposomes-peptide on SCC9 cells was performed and it was found that liposomal formulation was not cytotoxic. The antitumor efficacy of 186Re-liposomes, unlabelled liposomes, 186Re-perrhenate solution and 186Re-BMEDA solution was determined in SCC cell lines injected into BALB/c-nu/nu athymic nude rats. The efficacy of antitumor activity was found to be in the following order: peptide-conjugated DOX-loaded liposomes>unlabelled liposomes>186Re-perrhenate solution>186Re-BMEDA solution. The present investigation showed that peptide-conjugated DOX-loaded liposomes significantly suppress the tumor growth in the nude rat model. These results suggest the significant potential of liposomes as carriers for clinical applications in head and neck cancer.
本研究旨在开发用于头颈部癌症的多柔比星（DOX）负载脂质体递药系统。脂质体通过薄膜水化技术用卵磷 脂和胆固醇制备，采用 Box-Behnken 统计设计。对制备的脂质体进行包封效率、粒径和体外释放的评估。通过薄膜水化技术制备的 DOX 包封脂质体的平均粒径在 150.5nm 到 200nm 之间，平均粒径为 165.80nm。PDI（多分散指数）为 0.315，表明粒子是单分散和窄分散的。在磷酸盐缓冲盐水（pH7.4）中进行 DOX 负载脂质体和 DOX 负载肽偶联脂质体的体外药物释放，两种制剂在 40 小时内均表现出持续释放行为。优化的脂质体制剂与肽偶联，随后用 186Re-高铼酸盐溶液和 BMEDA-葡庚糖酸盐-氯化亚锡溶液进行放射性标记。对 DOX、DOX 脂质体和 DOX 脂质体-肽对 SCC9 细胞的比较细胞毒性试验表明，脂质体制剂没有细胞毒性。在 BALB/c-nu/nu 裸鼠中注射 SCC 细胞系，评价 186Re-脂质体、未标记脂质体、186Re-高铼酸盐溶液和 186Re-BMEDA 溶液的抗肿瘤疗效。抗肿瘤活性的疗效依次为：肽偶联 DOX 负载脂质体>未标记脂质体>186Re-高铼酸盐溶液>186Re-BMEDA 溶液。本研究表明，肽偶联 DOX 负载脂质体显著抑制裸鼠模型中的肿瘤生长。这些结果表明脂质体作为头颈部癌症临床应用载体具有重要潜力。
