A stimuli-responsive gradient-structured membrane for dual controlled release of bioactive agents: application to chronic wound dressings

Abstract

Currently, asymmetric polymeric membranes exhibit numerous advantages for wound dressing applications. Usually, numerous systems allow the release of only one or several antibacterial drugs to fight against the bacteria present on the wound. However, to be efficient, it is necessary to disrupt biofilm formation in order to render the enclosed bacteria sensitive to the antibacterial agent. Here, we describe a system capable of achieving such goal via a double compartment asymmetric polymeric membrane designed for dual drug release. In view of elaborating our gradient-structured membrane for differential kinetic release of combined antibiofilm/antibiotic agents in the context of wound dressing applications, a previously electrospun poly(vinyl alcohol) (PVA) fibrous membrane (EFM) was combined with a renewable poly(butylene-succinate-co-adipate) (PBSA) asymmetric porous membrane (AM) via physical adhesion. Physical adhesion was promoted via surface modification of the PVA fibers involving complexation of the numerous PVA hydroxyl groups with phenyl boronic acid (PBA). This modification resulted in heightened hydrophobicity of the upper EFM layer with substantial contact angle increase up to 115° allowing for effective adhesion of the PVA based EFM onto the AM. No delamination was observed. Thus, thanks to surface modification, a gradient-structured double compartment asymmetric membrane (DCAM) was obtained consisting of a dense/macro-/micro-/nano-porous structure. Furthermore, as proof of concept, our study shows that PBA can be used as a pro-drug mimic pH sensitive system exhibiting release profiles in aqueous environment up to 3-fold higher in acidic compared to that for neutral or alkaline environments. Moreover, the BSA (Bovine Serum Albumin) use as a potential therapeutic model protein was encapsulated within the porous structure and its release profile was monitored over time showing maximum release attained within 24 h. Finally, the biocompatibility of our new DCAM was confirmed via the internationally recognized standard ISO 10993-5: 2009 assay for the in vitro cytotoxicity testing of medical devices. Our results are promising in that they provide a new structural substrate for the dual concomitant differential-controlled release of large amounts of high (antibiofilm and potentially other therapeutic proteins) and low molecular weight (antibacterial) bioactive agents.