In vivo therapeutic evaluation of a cellulose acetate hydrogel cross linked with ethylenediaminetetraacetic-dianhydride containing propolis ethanolic-extract for treating burns

Abstract

An increasing interest in regenerative medicine has been an approach with natural products used for assorted skin treatments. Propolis from Apis mellifera species of bees have shown high acceptance due to antimicrobial and anti-inflammatory properties. However, just a few propolis types presents stronger effects in controlling inflammation. The current work describes an organic propolis recently isolated, named as OP6, that presented strong anti-inflammatory influences in vivo when associated with EDTA cross-linked hydrogel, used as a curative device in second-degree burns in a murine model. We developed a cellulose acetate hydrogel cross-linked with ethylenediaminetetraacetic dianhydride (HAC-EDTA) as a polymeric matrix for a bandage based on an ethanolic extract of propolis at 15%, 30%, and 60% (w/v) for treating second-degree burns. In vivo studies were carried out in Wistar rats divided into three groups: negative control (only lesion), positive control (lesion with HAC-EDTA film), and treatment group (lesion with the HAC-EDTA + OP6 at 15%, 30%, and 60%). Each group was randomized and equally subdivided into two subgroups according to the period of bandage wearing (7 and 14 days). Previous work of this research group selected the propolis OP6 sample source as the best candidate for the in vivo study. HAC-EDTA + OP6 15%, 30%, and 60% films demonstrated a concentration-dependent release rate, with the highest amount of propolis released after tests (484.3 mg) by HAC-EDTA enriched with the highest concentrated extract of propolis. HAC-EDTA + OP6 films were efficient in preventing infections, promoting lesion retraction, and tissue regeneration. The HAC-EDTA + OP6 30% treatment was more efficient, revealing a reduced inflammatory process and stimulating skin regeneration. The designed HAC-EDTA + propolis films were shown as promising tools for second-degree burns treatment, accelerating healing process to a full recovery tissue repair after 14 days.