Ionic liquid-mediated delivery of a BCL-2 inhibitor for topical treatment of skin melanoma

Md Nurul Huda, Isaac G. Deaguro, Edgar A. Borrego, Raj Kumar, Tamanna Islam, Humayra Afrin, Armando Varela-Ramirez, Renato J. Aguilera, Eden E.L. Tanner, Md Nurunnabi

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Skin melanoma is one of the most common cancer types in the United States and worldwide, and its incidence continues to grow. Primary skin melanoma can be removed surgically when feasible and if detected at an early stage. Anti-cancer drugs can be applied topically to treat skin cancer lesions and used as an adjunct to surgery to prevent the recurrence of tumor growth. We developed a topical formulation composed of Navitoclax (NAVI), a BCL-2 inhibitor that results in apoptosis, and an ionic liquid of choline octanoate (COA) to treat early-stage melanoma. NAVI is a small hydrophobic molecule that solubilizes at 20% (w/v) when dissolved in 50% COA. Although NAVI is a highly effective chemotherapeutic, it is equally thrombocytopenic. We found that COA-mediated topical delivery of NAVI enhanced its penetration into the skin and held the drug in the deeper skin layers for an extended period. Topical delivery of NAVI produced a higher cancer-cell killing efficacy than orally administrated NAVI. In vivo experiments in a mouse model of human melanoma-induced skin cancer confirmed the formulation's effectiveness via an apoptotic mechanism without any significant skin irritation or systemic absorption of NAVI. Overall, this topical approach may provide a safe and effective option for better managing skin cancer in the clinic.

Original languageEnglish
Pages (from-to)783-795
Number of pages13
JournalJournal of Controlled Release
Volume349
DOIs
StatePublished - Sep 2022
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2022 Elsevier B.V.

Funding

The research reported in this publication was supported by Cancer Prevention Research Institute of Texas (CPRIT) funding through a Texas Regional Excellence in Cancer Award (TREC) under Award No. PR210153 (MN). We also acknowledge funding by Research Centers at Minority Institutions grant funded by the National Institute on Minority Health and Health Disparities (NIMHD) of the National Institutes of Health (NIH) under Award No. U54MD007592 (AV-R, MN, RJA). The contents of this paper are solely the authors' responsibility and do not necessarily represent the official views of NCRR or NIH. We would like to thank the staff of the Cellular Characterization and Biorepository (CCB) Core Facility of UTEP for the services and facilities provided. EELT acknowledges the College of Liberal Arts at the University of Mississippi for funding. The research reported in this publication was supported by Cancer Prevention Research Institute of Texas (CPRIT) funding through a Texas Regional Excellence in Cancer Award (TREC) under Award No. PR210153 (MN). We also acknowledge funding by Research Centers at Minority Institutions grant funded by the National Institute on Minority Health and Health Disparities (NIMHD) of the National Institutes of Health (NIH) under Award No. U54MD007592 (AV-R, MN, RJA). The contents of this paper are solely the authors' responsibility and do not necessarily represent the official views of NCRR or NIH. We would like to thank the staff of the Cellular Characterization and Biorepository (CCB) Core Facility of UTEP for the services and facilities provided. EELT acknowledges the College of Liberal Arts at the University of Mississippi for funding.

FundersFunder number
Texas Regional Excellence in Cancer AwardPR210153
National Institutes of Health
National Center for Research Resources
Cancer Prevention and Research Institute of Texas
National Institute on Minority Health and Health DisparitiesU54MD007592
University of Mississippi
University of Texas at El Paso

    Keywords

    • Apoptosis
    • Chemotherapeutic
    • Ionic liquid
    • Melanoma
    • Topical delivery

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