Itraconazole for Topical Treatment of Skin Carcinogenesis: Efficacy Enhancement by Lipid Nanocapsule Formulations
Abstract
Itraconazole (ITC), an antifungal drug with anticancer activity, shows potential for oral treatment of skin cancer. There is clinical need for topical ITC for treating low-risk skin carcinogenesis. Our objective was to develop ITC nanoformulations with enhanced anticancer efficacy. Lipid nanocapsules (LNC), either unmodified (ITC/LNC) or modified with the amphiphiles miltefosine (ITC/MF-LNC) or the lipopeptide biosurfactant surfactin (ITC/SF-LNC) as bioactive additives were developed. LNC formulations showed high ITC entrapment efficiency (>98%), small diameter (42–45 nm) and sustained ITC release. Cytotoxicity studies using malignant SCC 9 cells and normal human fibroblasts (NHF) demonstrated significant enhancement of ITC anticancer activity and selectivity for cancer cells by the LNC formulations and a synergistic ITC-amphiphile interaction improving the combination performance. Treatment of intradermal tumor-bearing mice with the ITC nanoformulation gels compared with ITC and 5-FU gels achieved significant tumor growth inhibition that was remarkably enhanced by ITC/MF-LNC and ITC/SF-LNC as well as recovery of skin architecture. Molecularly, tumoral expression of Ki-67 and cytokeratin proliferative proteins was significantly suppressed by LNC formulations, the suppressive effect on cytokeratins was superior to that of 5-FU. These findings provide new evidence for effective topical treatment of low-risk skin carcinogenesis utilizing multiple approaches that involve drug repurposing, nanotechnology, and bioactive amphiphiles as formulation enhancing additives.
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A synergistic ITC-amphiphile interaction improved the combination performance.
“The LNC formulations significantly increased the ITC anticancer activity and selectivity for cancer cells, and a synergistic ITC–amphiphile interaction improved the combination performance, according to cytotoxicity experiments conducted using malignant SCC 9 cells and normal human fibroblasts (NHF).”
From Itraconazole as a repurposed anti-cancer agent: focusing on synthesis, mechanisms of action and therapeutic insights (2026) · cites this paper as [62]
The LNC formulations significantly increased the ITC anticancer activity and selectivity for cancer cells.
“The LNC formulations significantly increased the ITC anticancer activity and selectivity for cancer cells, and a synergistic ITC–amphiphile interaction improved the combination performance, according to cytotoxicity experiments conducted using malignant SCC 9 cells and normal human fibroblasts (NHF).”
From Itraconazole as a repurposed anti-cancer agent: focusing on synthesis, mechanisms of action and therapeutic insights (2026) · cites this paper as [62]
LNC formulations demonstrated sustained ITC release, a small diameter (42-45 nm), and a high ITC entrapment efficiency (>98%).
“LNC formulations demonstrated sustained ITC release, a small diameter (42–45 nm), and a high ITC entrapment efficiency (>98%).”
From Itraconazole as a repurposed anti-cancer agent: focusing on synthesis, mechanisms of action and therapeutic insights (2026) · cites this paper as [62]
ITC/MF-LNC and ITC/SF-LNC significantly increased the tumor growth suppression and skin architecture recovery of intradermal tumor-bearing mice treated with ITC nanoformulation gels as opposed to ITC and 5-FU gels.
“ITC/MF-LNC and ITC/SF-LNC significantly increased the tumor growth suppression and skin architecture recovery of intradermal tumor-bearing mice treated with ITC nanoformulation gels as opposed to ITC and 5-FU gels.”
From Itraconazole as a repurposed anti-cancer agent: focusing on synthesis, mechanisms of action and therapeutic insights (2026) · cites this paper as [62]
LNC formulations had a greater suppressive effect on cytokeratins than 5-FU and considerably reduced tumoral production of Ki-67 and cytokeratin proliferative proteins.
“LNC formulations had a greater suppressive effect on cytokeratins than 5-FU, and they considerably reduced tumoral production of Ki-67 and cytokeratin proliferative proteins.”
From Itraconazole as a repurposed anti-cancer agent: focusing on synthesis, mechanisms of action and therapeutic insights (2026) · cites this paper as [62]
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References 56 · Cited by 14
- Authors
- El-Sheridy, N. A., El-Moslemany, R. M., Ramadan, A. A., Helmy, M. W., & El-Khordagui, L. K.
- Affiliations
- Alexandria University (EG)
- Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt
- Damanhour University (EG)
- Venue
- Journal of Biomedical Nanotechnology
- Publisher
- American Scientific Publishers
- Published
- 2022-01-01
- Volume
- 18
- Issue
- 1
- Pages
- 97-111
- ISSN
- 1550-7033 (ISSN-L)
- OpenAlex
- W4212958195
- Cited by
- 14
- References
- 56
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 2 · 2023: 3
- FWCI
- 0.93
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Biomedical Nanotechnology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advancements in Transdermal Drug Delivery
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Health Sciences › Medicine › Epidemiology › Nonmelanoma Skin Cancer Studies
- Keywords
- itraconazole, lipid nanocapsules, miltefosine, surfactin, lipopeptide biosurfactant, drug repurposing, anticancer nanocarriers, sustained drug release, cytotoxicity, squamous cell carcinoma, Ki-67, cytokeratin, tumor growth inhibition, 5-fluorouracil
- MeSH terms
- Animals, Antifungal Agents, Lipids, Itraconazole, Mice, Nanocapsules, Carcinogenesis
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