Poly(vinyl alcohol) films for topical delivery of S‐nitrosoglutathione: Effect of freezing–thawing on the diffusion properties

Abstract

Poly(vinyl alcohol) (PVA) is a biocompatible polymer already used in several pharmaceutical products. The purpose of this work was to investigate the influence of freezing-thawing cycles (F/T) on the in vitro diffusion and skin vasodilator properties of S-nitrosoglutathione (GSNO)-releasing PVA films. Films subjected to 1-, 3-, and 5-F/T showed an increase in crystallinity, which is associated with an increase in the radius of gyration of macropores from 155 to 180 nm. Diffusion coefficients (D) of GSNO decreased from 5.7 x 10(-7) to 2.0 x 10(-7) cm(2) s(-1) in 1 and 3 F/T films, respectively, and were inversely correlated with the increase in crystallinity, whereas 5-F/T films showed an anomalous increase in D (5.0 x 10(-7) cm(2) s(-1)). Topical release of GSNO from PVA films on the skin of healthy volunteers led to local vasodilation measured by laser Doppler flowmetry. A higher increase in local blood flow was observed for 5-F/T films reaching maximum tissue perfusion at 45 min with return toward basal level after 45 min, whereas 1-F/T films led to a lower increase in blood flow up to 98 min. These results show that F/T treatment can be used to modulate the diffusion properties and the topical vasodilator profile of GSNO-containing PVA films, what might allow the use of these materials as dermal wound dressings or for promoting local vasodilation in ischemic tissues.

S-Nitrosoglutathione

“…GSNO has been administered through intravenous infusion [127], as an aerosolized inhalant [128], and more recently, as a topical gel [129] and poly vinyl alcohol film [130]. The best-characterized effects of GSNO in humans are on its direct and selective action in platelets.…”

Modulated nitric oxide delivery in three-dimensional biomaterials for vascular functionality

“…In a recent study done by Simoes and de Oliveira, PVA hydrogels with GSNO addition were prepared using the freezing-thawing (F/T) technique. [73] It was found that the pore size of PVA hydrogels decreased with increasing F/T cycles, whereas the crystallinity rose. NO diffusion coefficient depended not only on the pore size of the hydrogels, but also on the interconnectivity of the pores.…”

Polymer‐Based Nitric Oxide Therapies: Recent Insights for Biomedical Applications

“…PVA films (~50 mg) absorbed 450 μmol g −1 or 840 μmol g −1 of GSNO with one or five freeze/thawed (F/T) cycles, respectively. [166] Upon one F/T cycle, the crystallinity and physical cross-linking increased and was not different between one and five F/T cycles. However, the GSNO absorption and diffusion coefficient varied with F/T cycle number (one F/T: 2.0 · 10 −7 cm 2 s −1 , five F/T: 5.0 · 10 −7 cm 2 s −1 ), possibly because of greater interconnected pores with more cycles.…”