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.