Development of Polycaprolactone-Zeolite Nanoporous Composite Films for Topical Therapeutic Release of Different Gasotransmitters

Nitric oxide (NO) and hydrogen sulfide (H2S) are important signaling molecules present in all stages of wound healing, and their exogenous delivery presents an opportunity with high therapeutic potential. Herein, a polymeric film (polycaprolactone (PCL)) incorporating a nanoporous carrier (Zeolite 4A) was developed, presenting two possibilities for gas release therapy, using NO or H2S, to support a wide range of topical applications. Films were prepared containing different PCL:zeolite ratios, and a homogeneous distribution of the zeolite particles throughout the film was assured. Results show that films loaded with NO or H2S that are bonded to the zeolite microporous surface by chemical adsorption exhibit a sustained gas release in biological media (at least 3 h) due to the surrounding barrier created by the hydrophobic polymer. This composite design avoids the typical initial burst of gas release featured in most porous materials explored so far for NO/H2S therapy (e.g., Zeolite 4A itself releases all the NO/H2S adsorbed in the first 30 min). Cytotoxicity of gas-loaded PCL/zeolite films demonstrated a clear difference in biological action between gases. While NO released by the 30 mg mL(-1) film is non-toxic, H2S released by the same film at a 10 times lower concentration is in the threshold of being considered toxic (30% toxicity). These gas-loaded films also demonstrated potential antibacterial efficacy against E. coliat a non-toxic film concentration to mammalian cells.