Journal
CARBOHYDRATE POLYMERS
Volume 112, Issue -, Pages 376-386Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.carbpol.2014.05.026
Keywords
Hyaluronic acid; Nanoemulsion; 10,11-Methylenedioxycamptothecin; Transdermal delivery; Keloid fibroblast
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Funding
- International S&T Cooperation Program of China [2013DFG32880]
- National Natural Science Foundation of China [31000423, 31300786]
- Ministry of Education of China [20120132110012]
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This study designs an alternative transdermal delivery system for 10,11-methylenedioxycamptothecin(MD-CPT) to inhibit keloid. Hyaluronic acid nanoemulsions (HANs) with nano size, negative charge and good stability were prepared as transdermal carriers. The MD-CPT loaded HANs performed desirable skin permeable capacity across human keloid skin and the drug was transferred directly to keloid lesion area. MD-CPT was delivered percutaneously higher than the control group. FITC-HANs could be successfully internalized by keloid fibroblast (KF) and deliver MD-CPT toward nucleus, inhibited the proliferation of KF, while there was no serious toxicity to normal skin fibroblasts. The growth-inhibitory effect was further clarified upon cell cycle regulation, which arrested cells at G1/S and prevented them entry into mitosis. KF gene expression demonstrated plasminogen activator inhibitor-1 (PAI-1) was significantly down-regulated and Smad7 up-regulated, which was beneficial to inhibit keloid. The study demonstrated that as transdermal delivery of MD-CPT by HANs has potential for inhibition of keloid fibroblast. (C) 2014 Elsevier Ltd. All rights reserved.
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