Comprehensive Physicochemical Characterization, In Vitro Membrane Permeation, and In Vitro Human Skin Cell Culture of a Novel TOPK Inhibitor, HI-TOPK-032-Reference-Cited by-同舟云学术

Comprehensive Physicochemical Characterization, In Vitro Membrane Permeation, and In Vitro Human Skin Cell Culture of a Novel TOPK Inhibitor, HI-TOPK-032

Published:2023-10-24 Issue:21 Volume:24 Page:15515
ISSN:1422-0067
Container-title:International Journal of Molecular Sciences
language:en
Short-container-title:IJMS

Author:

Eedara Basanth Babu¹^ORCID,Manivannan Bhagyashree¹^ORCID,Alabsi Wafaa²³,Sun Bo²,Curiel-Lewandrowski Clara⁴⁵⁶^ORCID,Zhang Tianshun⁷^ORCID,Bode Ann M.⁷^ORCID,Mansour Heidi M.¹⁸⁹^ORCID

Affiliation:

1. Center for Translational Science, Florida International University, Port St. Lucie, FL 34987, USA

2. Skaggs Pharmaceutical Sciences Center, College of Pharmacy, The University of Arizona, Tucson, AZ 85721, USA

3. Department of Chemistry and Biochemistry, The University of Arizona, Tucson, AZ 85721, USA

4. Skin Cancer Institute, The University of Arizona Cancer Center, Tucson, AZ 85724, USA

5. University of Arizona Cancer Center, University of Arizona, Tucson, AZ 85724, USA

6. Department of Medicine, Division of Dermatology, College of Medicine, The University of Arizona, Tucson, AZ 85724, USA

7. The Hormel Institute, University of Minnesota, Austin, MN 55912, USA

8. Department of Environmental Health Sciences, Robert Stempel College of Public Health and Social Work, Florida International University, Miami, FL 33199, USA

9. Department of Cell Biology & Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL 33199, USA

Abstract

Nonmelanoma skin cancers (NMSC) are the most common skin cancers, and about 5.4 million people are diagnosed each year in the United States. A newly developed T-lymphokine-activated killer cell-originated protein kinase (TOPK) inhibitor, HI-TOPK-032, is effective in suppressing colon cancer cell growth, inducing the apoptosis of colon cancer cells and ultraviolet (UV) light-induced squamous cell carcinoma (SCC). This study aimed to investigate the physicochemical properties, permeation behavior, and cytotoxicity potential of HI-TOPK-032 prior to the development of a suitable topical formulation for targeted skin drug delivery. Techniques such as scanning electron microscopy (SEM), energy-dispersive X-ray (EDX) spectroscopy, differential scanning calorimetry (DSC), hot-stage microscopy (HSM), X-ray powder diffraction (XRPD), Karl Fisher (KF) coulometric titration, Raman spectrometry, confocal Raman microscopy (CRM), attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), and Fourier transform infrared microscopy were used to characterize HI-TOPK-032. The dose effect of HI-TOPK-032 on in vitro cell viability was evaluated using a 2D cell culture of the human skin keratinocyte cell line (HaCaT) and primary normal human epidermal keratinocytes (NHEKs). Transepithelial electrical resistance (TEER) at the air–liquid interface as a function of dose and time was measured on the HaCAT human skin cell line. The membrane permeation behavior of HI-TOPK-032 was tested using the Strat-M® synthetic biomimetic membrane with an in vitro Franz cell diffusion system. The physicochemical evaluation results confirmed the amorphous nature of the drug and the homogeneity of the sample with all characteristic chemical peaks. The in vitro cell viability assay results confirmed 100% cell viability up to 10 µM of HI-TOPK-032. Further, a rapid, specific, precise, and validated reverse phase-high performance liquid chromatography (RP-HPLC) method for the quantitative estimation of HI-TOPK-032 was developed. This is the first systematic and comprehensive characterization of HI-TOPK-032 and a report of these findings.

Funder

NIH

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

Link

https://www.mdpi.com/1422-0067/24/21/15515/pdf

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