Design, Physicochemical Characterization, and In Vitro Permeation of Innovative Resatorvid Topical Formulations for Targeted Skin Drug Delivery
Sherry Chow, H.-H.
AffiliationDepartment of Pharmacology and Toxicology, The University of Arizona College of Pharmacy
University of Arizona Cancer Center, University of Arizona
Department of Medicine, Division of Hematology and Oncology, The University of Arizona College of Medicine
Department of Medicine, Division of Dermatology, The University of Arizona College of Medicine
BIO5 Institute, University of Arizona
Department of Medicine, Division of Translational & Regenerative Medicine, The University of Arizona College of Medicine
Epiderm™ 3D human skin
HaCaT human skin cell line
hyaluronic acid (HA) gel
in vitro cell viability
NHEK normal primary human skin cells
nonmelanoma skin cancers
Pluronic® poloxamer triblock copolymer
polyethylene glycol (PEG)
propylene glycol (PG)
Strat-M synthetic membrane
topical drug delivery
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CitationRuiz, V. H., Encinas-Basurto, D., Sun, B., Eedara, B. B., Dickinson, S. E., Wondrak, G. T., Sherry Chow, H.-H., Curiel-Lewandrowski, C., & Mansour, H. M. (2022). Design, Physicochemical Characterization, and In Vitro Permeation of Innovative Resatorvid Topical Formulations for Targeted Skin Drug Delivery. Pharmaceutics.
RightsCopyright © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
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AbstractNonmelanoma skin cancers (NMSCs) are the most common malignancies worldwide and affect more than 5 million people in the United States every year. NMSC is directly linked to the excessive exposure of the skin to solar ultraviolet (UV) rays. The toll-like receptor 4 (TLR4) antago-nist, resatorvid (TAK-242), is a novel prototype chemo preventive agent that suppresses the production of inflammation mediators induced by UV exposure. This study aimed to design and de-velop TAK-242 into topical formulations using FDA-approved excipients, including DermaBase™, PENcream™, polyethylene glycol (PEG)-400, propylene glycol (PG), carbomer gel, hyaluronic acid (HA) gel, and Pluronic® F-127 poloxamer triblock copolymer gel for the prevention of skin cancer. The physicochemical properties of raw TAK-242, which influence the compatibility and solubility in the selected base materials, were confirmed using X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), hot-stage microscopy (HSM), Raman spectroscopy, and attenuated to-tal reflectance Fourier-transform infrared (ATR-FTIR) spectroscopic analysis. The permeation behavior of TAK-242 from the prepared formulations was determined using Strat-M® transdermal diffusion membranes, and 3D cultured primary human-derived epidermal keratinocytes (Epi-Derm™). Despite TAK-242′s high molecular weight and hydrophobicity, it can permeate through reconstructed human epidermis from all formulations. The findings, reported for the first time in this study, emphasize the capabilities of the topical application of TAK-242 via these multiple innovative topical drug delivery formulation platforms. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
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Except where otherwise noted, this item's license is described as Copyright © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).