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

Abstract

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.

Evaluation of an Imine-Linked Polymer Organic Framework for Storage and Release of H2S and NO

“…Due to experimental limitations, the isotherm of the H 2 S could not be determined, yet it was possible to determine the maximum adsorption capacity, which had a value of 0.97 mmol/g. This value is of the same order of magnitude as the value obtained for the best PCL/4A zeolite composite [ 34 ] and higher than that observed for the mesoporous SBA-15, which had a higher A BET and higher pore opening [ 7 ]. The presence of amines in the i-POF structure may contribute to the adsorption process since the amine affinity for H 2 S is well known.…”

“…The amount of NO adsorbed by the i-POF was greater than that of the PCL/4A composites and comparable with the 4A zeolite (at 20 h). On the other hand, the amount of NO release was intermediate between the PCL/4A composite (15%) and 4A zeolite (38%) [ 34 ]. Concerning the NO adsorption by MIP-177 and vitamin B 3 MOF, the i-POF had a lower adsorption and NO release capacity [ 42 , 43 ].…”

“…The determination of the H 2 S isotherm was not possible due to slow kinetics. Therefore, only the maximum adsorption is shown, as described in [ 34 ]. The NO adsorption was measured for up to 20 h in order to make a more accurate comparison with the H 2 S adsorption.…”

“…The prior outgassing was conducted using the same conditions as the adsorption studies. The loading of the material with H 2 S/NO used the procedure already described in [ 34 , 35 ].…”

“…These two methodologies are appropriate for these studies since they allow detecting the presence of H 2 S and NO at physiological pH (pH = 7.2). The preparation of the solutions and the detailed experimental procedures are described elsewhere [ 34 , 35 ]. Briefly, the DTNB methodology is based on the absorbance (408 nm) of the anion 5-thio-2-nitrobenzoate formed in the reaction between DTNB and H 2 S [ 36 ].…”