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• W4289313647 endingPage "1607" @default.
• W4289313647 startingPage "1607" @default.
• W4289313647 abstract "Infantile hemangiomas (IH) leave sequelae after involution. Topical application of timolol maleate (TM) is the mainstream treatment for superficial lesions but is limited by its low penetrable properties. We aimed to develop a superior skin permeation drug while maintaining the therapeutic properties of timolol. We predict that this drug will promote the involution of thick and deep IH lesions and avoid sequelae. We chemically modified drug structure to prepare butyryl timolol maleate (BT) prodrug and conducted in vitro and in vivo toxicity evaluations of BT with rat dorsal skin and normal skin cells. Skin permeation and absorption comparisons of TM and BT were conducted using rat and porcine skin models. Conversion efficiency of BT to timolol was also tested on human skin ex vivo. BT did not cause skin irritation on rat dorsal skin and exhibited low cytotoxicity overall. BT exhibited superior skin permeation ability compared with that of TM, whilst maintaining a low systemic absorbance. Further, BT was converted to timolol in human skin in a time-dependent manner. Noticeably, timolol accumulation in the skin from BT was higher than that from TM. Finally, BT demonstrated similar biocompatibility with TM in the IH tumor. BT enhances local delivery of timolol and its skin permeation. Using BT, we could eliminate thicker IH lesions that are prone to leave sequelae, and potentially help young children avoid dermal sequelae, disfigurement, and concomitant therapy." @default.
• W4289313647 created "2022-08-02" @default.
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• W4289313647 date "2022-08-01" @default.
• W4289313647 modified "2023-09-25" @default.
• W4289313647 title "Evaluation of Transdermal Transport and Concurrent Cutaneous Hydrolysis of Timolol Prodrug for the Treatment of Infantile Hemangiomas" @default.
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• W4289313647 doi "https://doi.org/10.3390/pharmaceutics14081607" @default.
• W4289313647 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36015233" @default.
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