Enhanced performance of gelatin 5-fluorouracil-containing nanoparticles against squamous cell carcinoma in simulated chronic wounds conditions.

Chronic wounds are considered a silent epidemic affecting a significant fraction of the World population. Their treatment supposes a large fraction of the public spending on the health of developed countries. In chronic wounds secondary to burns, trauma, UV light radiation, and diabetes, among others, the development of squamous cell carcinoma (SCC) has been reported. If detected early, 95% of SCC are most comfortable to be treated and cured; however, 5% of advanced SCC is more dangerous and challenging to treat. It has been reported that the pH value within the wound-milieu influences indirectly and directly all biochemical reactions taking place in this process of healing. Differences in pH values between normal skin and chronic cutaneous wounds could be considered in designing and developing stimuli-responsive nanomaterials. In this work, the anticancer drug 5-fluorouracil (5-FU) inclusion on gelatin-based NPs for SCC treatment has been projected. The present work goal is to prepare and characterize physicochemical and biological properties of new therapeutic-containing NPs for the sustainable delivery of 5-FU under simulated chronic wound conditions. In vitro experiments have been performed to assess the biocompatible character of these gelatin-based NPs in terms of their hemolytic and cytotoxicity properties. Due to hyperglycemia impact on both the chronicity of the wounds and chemotherapy efficacy, cellular responses have been determined under euglycemic and hyperglycemic conditions. In vitro cytotoxicity studies have reported good selective toxicity against the A431 cell line, demonstrating that gelatin-based NPs are promising dual-responsive delivery systems to SCC targeting under simulated chronic wound conditions.