Design, Physicochemical Characterization, and In Vitro Permeation of Innovative Resatorvid Topical Formulations for Targeted Skin Drug Delivery.

TitleDesign, Physicochemical Characterization, and In Vitro Permeation of Innovative Resatorvid Topical Formulations for Targeted Skin Drug Delivery.
Publication TypeJournal Article
Year of Publication2022
AuthorsRuiz VH, Encinas-Basurto D, Sun B, Eedara BBabu, Dickinson SE, Wondrak GT, Chow H-HSherry, Curiel-Lewandrowski C, Mansour HM
JournalPharmaceutics
Volume14
Issue4
Date Published2022 Mar 24
ISSN1999-4923
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) antagonist, 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 develop 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 total 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 (EpiDerm). 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.

DOI10.3390/pharmaceutics14040700
Alternate JournalPharmaceutics
PubMed ID35456534
PubMed Central IDPMC9026853
Grant ListP01 CA229112 / CA / NCI NIH HHS / United States
NIH NCI P01CA229112 NCI P01CA229112-02S1 / NH / NIH HHS / United States
Faculty Member Reference: 
Sally Dickinson, Ph.D.