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 language | English |
|---|---|
| Pages (from-to) | 783-795 |
| Number of pages | 13 |
| Journal | Journal of Controlled Release |
| Volume | 349 |
| DOIs | |
| State | Published - Sep 2022 |
| Externally published | Yes |
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.
| Funders | Funder number |
|---|---|
| Texas Regional Excellence in Cancer Award | PR210153 |
| National Institutes of Health | |
| National Center for Research Resources | |
| Cancer Prevention and Research Institute of Texas | |
| National Institute on Minority Health and Health Disparities | U54MD007592 |
| University of Mississippi | |
| University of Texas at El Paso |
Keywords
- Apoptosis
- Chemotherapeutic
- Ionic liquid
- Melanoma
- Topical delivery
