Hyaluronic Acid Derivative-Based Self-Assembled Nanoparticles for the Treatment of Melanoma |
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Authors: | Yu-Jin Jin Ubonvan Termsarasab Seung-Hak Ko Jae-Seong Shim Saeho Chong Suk-Jae Chung Chang-Koo Shim Hyun-Jong Cho Dae-Duk Kim |
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Institution: | 1. College of Pharmacy Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 151-742, Republic of Korea 2. Biogenics Inc., Daejeon, 305-510, Republic of Korea 3. Skin & Tech Inc., Seongnam, 461-713, Republic of Korea 4. College of Pharmacy, Sunchon National University, Suncheon, 540-950, Republic of Korea
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Abstract: | Purpose Hyaluronic acid-ceramide (HACE)-based nanoparticles (NPs) were developed for the targeted delivery of doxorubicin (DOX), and their antitumor efficacy for melanoma was evaluated. Methods DOX-loaded HACE-based self-assembled NPs were prepared and their physicochemical properties were characterized. The in vitro cytotoxicity of HACE was measured using an MTS-based assay. The cellular uptake efficiency of DOX into mouse melanoma B16F10 cells was assessed by confocal laser scanning microscopy and flow cytometry. Tumor growth and body weight were monitored after the intratumoral and intravenous injection of DOX-loaded NPs into a B16F10 tumor-bearing mouse model. Results DOX-loaded NPs, with a mean diameter of ~110?nm, a narrow size distribution, and high drug entrapment efficiency, were prepared. A sustained DOX release pattern was shown, and drug release was enhanced at pH 5.5 compared with pH 7.4. The cytotoxicity of HACE to B16F10 cells was negligible. It was assumed that DOX was taken up into the B16F10 cells through receptor-mediated endocytosis. A significant inhibitory effect was observed on tumor growth, without any serious changes in body weight, after the injection of DOX-loaded NPs into the B16F10 tumor-bearing mouse model. Conclusions DOX-loaded HACE-based NPs were successfully developed and their antitumor efficacy against B16F10 tumors was demonstrated. |
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