Journal
CARBOHYDRATE POLYMERS
Volume 246, Issue -, Pages -Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.carbpol.2020.116650
Keywords
Dextran methacrylate; Hydrogel; Microneedles; Doxorubicin; Trametinib; MDR; Melanoma
Categories
Funding
- Natural Science Foundation of China [31870943]
- Science and Technology Project of Guangdong Province [2018A050506040, 2018A050506019, 2018A050506021]
- Science and Technology Program of Guangzhou [201907010032, 201907010037]
- Pearl River S&T Nova Program of Guangzhou [201710010155, 201806010072]
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Microneedles (MNs) technology has many advantages and is an ideal local transdermal drug delivery method. Here we synthesized photocrosslinkable dextran methacrylate (DexMA), and its degree of substitution is 5 % higher than the previous method. We used DexMA hydrogel for the first time to develop a new type of MNs for continuous transdermal administration. The prepared hydrogel MNs can successfully penetrate the epidermal layer and achieve sustained drug release. Doxorubicin (DOX) and trametinib (Tra) are anticancer drugs approved by FDA. Besides, Tra can also reverse P-gp-mediated multidrug resistance (MDR) to effectively block the efflux of DOX by P-gp. We used MNs to simultaneously load Tra and DOX, and achieved synergy in a B16 cell xenograft nude mouse model. The DexMA hydrogel MNs developed in this study can be used to enhance the transdermal delivery of small molecule drugs and reduce systemic toxicity and side effects.
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