Biodegradable polymer casting films for drug delivery and cell culture

Abstract

In this work, for the first time, films were obtained based on biodegradable polyhydroxyalkanoates (PHAs) - a copolymer of 3-hydroxybutyrate-co-3-hydroxyvalerate P(3HB-co-3HV) and a copolymer of 3-hydroxybutyrate-co-4-hydroxybutyrate P(3HB-co-4HB), containing drugs of different chemical structure and action - antibiotics (ceftazidime, doripenem), antiseptic (chlorhexidine) and tissue regeneration stimulator (Actovegin) for drug delivery and cell culture. Using SEM, AFM and measuring the contact angles of water wetting, it is shown how PHAs composition and loading of films of P(3HB-co-3HV) and P(3HB-co-4HB) with drugs affect the porosity, roughness indicators and adhesive properties of the surface. The constructed films are a depot form of drug, the release of which in vitro is realized for a long time, without burst releases, corresponds to Korsmeyer-Peppas and Higuchi models with diffusion character. Films loaded with antibiotics have pronounced antibacterial activity and suppress the development of pathogens S. aureus and E. coli, without a pronounced negative effect on the adhesion and proliferation of epidermal cells. In the cultures of human keratinocytes HaCaT it was shown that the presence of actovegin, as well as ceftazidime in the films, exhibits a stimulating effect, increasing their number. The results demonstrate the suitability of the depot-films for cellular technologies and are promising for the reconstruction of tissues complicated by infection.