Design, Physicochemical Characterization, and In Vitro Permeation of Innovative Resatorvid Topical Formulations for Targeted Skin Drug Delivery
Name:
pharmaceutics-14-00700-v2.pdf
Size:
5.445Mb
Format:
PDF
Description:
Final Published Version
Author
Ruiz, 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.
Affiliation
Department of Pharmacology and Toxicology, The University of Arizona College of PharmacyUniversity 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
Issue Date
2022Keywords
carbomer gelcream
diffusion
emulsion
Epiderm™ 3D human skin
flux
Franz cell
HaCaT human skin cell line
hyaluronic acid (HA) gel
hydrogel
in vitro cell viability
NHEK normal primary human skin cells
nonmelanoma skin cancers
Pluronic® poloxamer triblock copolymer
polyethylene glycol (PEG)
propylene glycol (PG)
resatorvid (TAK-242)
retention
Strat-M synthetic membrane
topical drug delivery
Metadata
Show full item recordPublisher
MDPICitation
Ruiz, 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.Journal
PharmaceuticsRights
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/).Collection Information
This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.Abstract
Nonmelanoma 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.Note
Open access journalISSN
1999-4923Version
Final published versionae974a485f413a2113503eed53cd6c53
10.3390/pharmaceutics14040700
Scopus Count
Collections
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/).