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Open AccessArticle

Glycol Chitosan-Docosahexaenoic Acid Liposomes for Drug Delivery: Synergistic Effect of Doxorubicin-Rapamycin in Drug-Resistant Breast Cancer

1
International Research Organization for Advanced Science and Technology (IROAST), Kumamoto University, Kumamoto 860-8555, Japan
2
Faculty of Advanced Science and Technology, Kumamoto University, Kumamoto 860-8555, Japan
*
Author to whom correspondence should be addressed.
Mar. Drugs 2019, 17(10), 581; https://doi.org/10.3390/md17100581
Received: 2 October 2019 / Revised: 8 October 2019 / Accepted: 11 October 2019 / Published: 12 October 2019
(This article belongs to the Special Issue Nano-Marine Drugs: Relevance of Nanoformulations in Cancer Therapies)
Marine ecosystems are the most prevalent ecosystems on the planet, providing a diversity of living organisms and resources. The development of nanotechnology may provide solutions for utilizing these thousands of potential compounds as marine pharmaceuticals. Here, we designed a liposomal glycol chitosan formulation to load both doxorubicin (DOX) and rapamycin (RAPA), and then evaluated its therapeutic potential in a prepared drug-resistant cell model. We explored the stability of the drug delivery system by changing the physiological conditions and characterized its physicochemical properties. The electrostatic complexation between DOX-glycol chitosan and docosahexaenoic acid RAPA-liposomes (GC-DOX/RAPA ω-liposomes) was precisely regulated, resulting in particle size of 131.3 nm and zeta potential of −14.5 mV. The well-characterized structure of GC-DOX/RAPA ω-liposomes led to high loading efficiencies of 4.1% for DOX and 6.2% for RAPA. Also, GC-DOX/RAPA ω-liposomes exhibited high colloidal stability under physiological conditions and synergistic anti-cancer effects on DOX-resistant MDA-MB-231 cells, while showing pH-sensitive drug release behavior. Our results provided a viable example of marine pharmaceuticals with therapeutic potential for treating drug-resistant tumors using an efficient and safe drug delivery system. View Full-Text
Keywords: marine pharmaceuticals; glycol chitosan; nanoliposome; combinatorial therapy; drug resistance; drug delivery; cancer therapy marine pharmaceuticals; glycol chitosan; nanoliposome; combinatorial therapy; drug resistance; drug delivery; cancer therapy
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MDPI and ACS Style

Kim, M.W.; Niidome, T.; Lee, R. Glycol Chitosan-Docosahexaenoic Acid Liposomes for Drug Delivery: Synergistic Effect of Doxorubicin-Rapamycin in Drug-Resistant Breast Cancer. Mar. Drugs 2019, 17, 581.

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  • Externally hosted supplementary file 1
    Doi: 10.5281/zenodo.3475643
    Link: https://zenodo.org/record/3475643#.XZvXQ0YzaUl
    Description: Figure S1: The images of GC-DOX/RAPA ω-liposome sample at different ratios after centrifugation. Figure S2: Colloidal stability of GC-DOX/RAPA ω-liposomes at pH 7.4 and pH 4 in 10% FBS. Figure S3: Drug combination index analysis for selected DOX and RAPA ratio (1:1.5) in MDA-MB-231-GFP/DOX cell lines. Table S1: Components of GC-DOX/RAPA ω-liposomes.
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