Methotrexate-Loaded solid lipid nanoparticles enhance the viability of cutaneous flaps: potential for surgical wound healing

Author(s)

Camargo, Cristina Pires ; Guido, Maria Carolina ; Tavares, Elaine Rufo ; Carvalho, Priscila Oliveira ; Gemperli, Rolf ; Maranhao, Raul Cavalcante

• Document type: Journal article
• Source: Journal of Drug Targeting; v. N/A, p. 9-pg., 2024-09-26.

Abstract

Skin flaps are employed to cover cutaneous denuded surfaces, but ensuing flap necrosis often occurs. Previously, rats with myocardial infarction treated with lipid-core nanoparticles (LDE) loaded with methotrexate (MTX) improved myocardial irrigation and reduced necrosis. Here, the aim was to investigate the efficacy of LDE-MTX to preserve the viability of cutaneous flaps and its implications for surgical wound healing. Twenty-eight male rats were divided into 4 groups: (1) LDE, injected intraperitoneally with LDE only; (2) MTX (1 mg/Kg commercial MTX): (3) LDE-MTX (1 mg/Kg MTX associated with LDE), and controls without treatment. LDE, MTX or LDE-MTX were repeated after 2 days. Then, flap surgery (9x3cm) was performed on the dorsal region. Injections were continued every other day until day 7 when animals were euthanized. LDE-MTX treatment improved the total viable area of the flaps with a fourfold increase in blood flow and reduced inflammatory cell number (p < 0.001), accompanied by decreased protein expression of pro-inflammatory factors. SOD-1 was higher in LDE-MTX-treated rats (p < 0.05). In conclusion, LDE-MTX treatment achieved total viability of cutaneous flaps, with increased irrigation and diminished local inflammation. LDE-MTX may offer efficient and cost-effective prevention of cutaneous flaps and treatment for wounds from surgical procedures to be tested in future clinical studies. (AU)

• FAPESP's process: 20/16215-0 - Lipid core nanoparticles (LDE) as vehicles of chemotherapeutic agents: a new standard for the medical therapeutics
• Grantee: Raul Cavalcante Maranhao
• Support Opportunities: Research Projects - Thematic Grants