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- W4366185802 abstract "Treatment of skin neoplastic conditions with topical chemotherapy often results in skin erythema, swelling, and desquamation. These skin reactions are marked by excessive oxidative stress and in severe cases lead to pain and impaired wound healing. We have shown that topical application of synthetic melanin nanoparticles (SMP) facilitates repair through scavenging ROS and downregulating pro-inflammatory pathways in the skin. Melanin is natural heterogenous polymer that is an efficient free radical scavenger, thus making it an attractive biomimetic platform for the development of new treatments aimed at battling the detrimental effects of oxidative stress. To further enhance SMPs, we developed their hydrophobic versions (hSMP) to promote closer contact interactions with the stratum corneum. SMPs were modified post-polymerization via reaction with a primary alkyl amine, conferring hydrophobicity to the particle with minimal impact to morphology and radical scavenging activity. These modifications allow hSMPs to be compounded in excipients such as squalene, found in human sebum, and its hydrogenated more stable version squalane. Using a chemical skin injury model with topical nitrogen mustard (NM), we observed that application of hSMPs in squalane significantly decreased skin edema at days 2, 3 and 5 post injury (n=5, p=0.03, 0.04, and 0.03 respectively) compared to the unmodified SMP and vehicle control. Analysis of skin wounds by qRT-PCR for hallmark inflammatory gene signatures previously identified from our human NM clinical trial demonstrated significantly decreased expression of IL1b (p=0.01), MMP9 (p=0.04), OSM (p=0.01) in the hSMP+squalane treated mice compared to controls. Altogether, our data show that formulation of hydrophobic SMP in squalane improve toxic reactions from chemotherapy and can be potentially developed into topical adjuvants to mitigate the side-effects of physician-directed therapies." @default.
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- W4366185802 date "2023-05-01" @default.
- W4366185802 modified "2023-09-28" @default.
- W4366185802 title "1125 Novel hydrophobic melanin particles improve wound repair" @default.
- W4366185802 doi "https://doi.org/10.1016/j.jid.2023.03.1137" @default.
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