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Chitosan–alginate BSA-gel-capsules for local chemotherapy against drug-resistant breast cancer

Authors Shen H, Li F, Wang D, Yang Z, Yao C, Ye Y, Wang X

Received 24 November 2017

Accepted for publication 16 February 2018

Published 19 April 2018 Volume 2018:12 Pages 921—934

DOI https://doi.org/10.2147/DDDT.S158001

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Georgios D. Panos


Haijun Shen,1 Fang Li,1 Dongxia Wang,1 Zhihan Yang,1 Chunfang Yao,1 Yang Ye,1 Xiaona Wang2

1Department of Preventive Medicine and Public Health Laboratory Science, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu Province, China; 2Department of Internal Medicine of Jiangsu University Hospital Workers, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, China

Background and object: 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.
Method: 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.
Result: 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.
Conclusion: 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.

Keywords: polyelectrolyte capsule, bovine serum albumin, layer-by-layer, pH-responsive, intratumor injection, multidrug resistance

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