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.