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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 reviewers approved by Dr Govarthanan Muthusamy
Peer reviewer comments 2
Editor who approved publication: Dr Georgios Panos
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