Chitosan-alginate BSA-gel-capsules for local chemotherapy against drug-resistant breast cancer.
Chitosan-alginate BSA-gel-capsules for local chemotherapy against drug-resistant breast cancer.
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壳聚糖-海藻酸盐 BSA-凝胶胶囊用于抗耐药乳腺癌局部化疗
DOI：
10.2147/dddt.s158001
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Wang X
中科院分区：
文献类型：
--
作者：
Shen H;Li F;Wang D;Yang Z;Yao C;Ye Y;Wang X
聚电解质微胶囊是一种很有前途的多功能给药系统。然而，缺乏关于动物实验的报道大大减缓了它们用于药物输送的发展。我们设计了以牛血清白蛋白凝胶填充的可生物降解壳聚糖-海藻酸盐聚电解质多层胶囊（bsa -凝胶胶囊）。在这里，我们证明了它们在局部化疗中的适用性，局部化疗是一种通过在肿瘤部位直接施用抗肿瘤药物来治疗局部或区域恶性肿瘤的方法。将多柔比星（DOX）装入bsa凝胶胶囊中，利用DOX耐药细胞系（MCF-7/ADR细胞）进行体外抗肿瘤研究。研究了bsa凝胶胶囊中DOX的细胞毒性、细胞摄取和分布。建立裸鼠MCF-7/ADR异种移植瘤模型。然后评价载dox的bsa凝胶胶囊瘤内注射的体内抗肿瘤效果。与游离DOX相比，负载DOX的bsa凝胶胶囊对MCF-7/ADR细胞具有更有效的细胞毒性，显示出正向的耐药逆转作用。此后，MCF-7/ADR细胞中bsa凝胶胶囊中DOX的更多细胞摄取和细胞核分布为逆转作用提供了令人信服的解释。在MCF-7/ADR细胞异种移植小鼠中，负载DOX的bsa凝胶胶囊的抗肿瘤效果明显优于游离DOX。最后，局部给药后，BSA-gel-capsules在肿瘤部位的高DOX积累和长时间滞留，显示了BSA-gel-capsules在局部化疗中的独特优势。这些发现表明，载dox的bsa凝胶胶囊应该被认为是治疗耐药乳腺癌的潜在候选药物。本文为聚电解质微胶囊局部化疗提供了可行性，为其作为药物传递载体的应用迈出了一大步。
Polyelectrolyte microcapsule is a promising candidate for multifunctional drug delivery system. However, the lack of reports about animal experiments have greatly slowed down their development for drug delivery. We engineered biodegradable chitosan–alginate polyelectrolyte multilayer capsule filled with bovine serum albumin gel (BSA-gel-capsule). Herein, we demonstrated their applicability for local chemotherapy, a means of treating local or regional malignancies by direct administration of anti-tumor agents to tumor sites. Doxorubicin (DOX) was loaded in BSA-gel-capsules and DOX-resistant cell line (MCF-7/ADR cells) was employed for antitumor studies in vitro. The cytotoxicity, cellular uptake and distribution of DOX from BSA-gel-capsules were studied. Afterwards, MCF-7/ADR xenografts tumor model was established in nude mice. The in vivo antitumor efficacy of DOX-loaded BSA-gel-capsules by intratumor injection was then evaluated. Compared with free DOX, more effective cytotoxicity against MCF-7/ADR cells after treatment with DOX-loaded BSA-gel-capsules was revealed, demonstrating the positive reversal effect on drug-resistance. Thereafter, the more cellular uptake and nucleus distribution of DOX from BSA-gel-capsules in MCF-7/ADR cells provided convincing explanation for the reversal effect. DOX-loaded BSA-gel-capsules displayed remarkably more antitumor efficacy than free DOX in MCF-7/ADR cell-xenografted mice. Finally, the high DOX accumulation and prolonged retention in tumor site after local administration of DOX-loaded BSA-gel-capsules was demonstrated, displaying the unique advantages of BSA-gel-capsules for local chemotherapy. These findings indicate that DOX-loaded BSA-gel-capsules should be considered a potential candidate for the treatment of drug-resistant breast cancer. This paper provides a feasibility for the local chemotherapy of polyelectrolyte microcapsules, which will be a big step towards their application as drug delivery vehicles.