Thin films of cross-linked polylactic acid as tailored platforms for controlled drug release

Abstract

Drug-loaded polymers are desirable for the controlled administration of bioactive molecules to biological media because polymer viscoelasticity can be translated into benefits of tissue-contacting materials. Here, we report on plasma-assisted deposition of polyester thin films performed via thermal evaporation of polylactic acid (PLA). The films can be produced with the chemical composition and polymer topology precisely tuned by the discharge power. At low power, weakly cross-linked films are produced with the chemical motif resembling that of PLA, the molar mass distribution peaking at ~350 g × mol−1 and skewing to larger species. At high power, highly cross-linked films are produced with a worse resemblance to PLA. The films swell and dissolve in water, releasing oligomers with the dissolution kinetics spanning over a broad time scale of 10−1–104 s. The released oligomers undergo hydrolysis at the time scale of days and with the final product of lactic acid, meeting the biocompatibility demands. When dissolving, the films expose micrometre-sized pores or buckling instabilities, depending on the discharge power. The phenomenon can be used for controlled release of nisin, an antibacterial peptide so that an hour-delayed release is achieved via the pore-mediated diffusion, whereas a minute-delayed release is achieved through the buckling. Nisin-loaded polyester plasma polymer films are effective against Micrococcus luteus, the bactericidal activity correlating with the drug release kinetics. Hence, the film design holds promise for developing advanced wound dressing materials and other tissue-contacting devices with tunable therapeutic effect. © 2021 Elsevier B.V.Czech Science FoundationGrant Agency of the Czech Republic [GA17-10813S]; Charles University [SVV 260 579/2021]; Ministry of Industry and Trade of the Czech Republic [TRIO FV10400]Univerzita Karlova v Praze, UK: SVV 260 579/2021; Grantová Agentura České Republiky, GA ČR: GA17-10813S; Ministerstvo Průmyslu a Obchodu, MPO: TRIO FV1040