Characterization and Evaluation of Zero-Order Release System Comprising Glycero-(9,10-trioxolane)-trialeate and PLA: Opportunity for Packaging and Biomedicine Applications

Glycerol-(9,10-trioxolane) trioleate (OTOA) is a promising material that combines good plasticizing properties for PLA with profound antimicrobial activity, which makes it suitable for application in state-of-the-art biomedical and packaging materials with added functionality. On the other hand, application of OTOA in PLA-based antibacterial materials is hindered by a lack of knowledge on kinetics of the OTOA release. In this work, the release of glycero-(9,10-trioxolane) trioleate (OTOA) from PLA films with 50% OTOA content was studied during incubation in normal saline solution, and for the first time, the kinetics of OTOA release from PLA film was evaluated. Morphological, thermal, structural and mechanical properties of the PLA + 50% OTOA films were studied during incubation in normal saline and corresponding OTOA release using differential scanning calorimetry (DSC), X-ray diffraction (XRD), Fourier-transform infrared (FTIR) spectroscopy and mechanical tests. It was confirmed by DSC and XRD that incubation in the saline solution and corresponding OTOA release from PLA film does not lead to significant changes in the structure of the polymer matrix. Thus, the formation of more disturbed α' crystalline phase of PLA due to partial hydrolysis of amorphous zones and/or most unstable crystallites in the PLA/OTOA semi-crystalline structure was observed. The degree of crystallinity of PLA + OTOA film was also slightly increased at the prolonged stages of OTOA release. PLA + 50% OTOA film retained its strength properties after incubation in normal saline, with a slight increase in the elastic modulus and tensile strength, accompanied by a significant decrease in relative elongation at break. The obtained results showed that PLA + 50% OTOA film could be characterized by sustained OTOA release with the amount of released OTOA exceeding 50% of the initial content in the PLA film. The OTOA release profile was close to zero-order kinetics, which is beneficial in order to provide stable drug release pattern. Developed PLA + 50% OTOA films showed a strong and stable antibacterial effect against <i>Raoultella terrigena</i> and <i>Escherichia coli</i>, bacterial strains with multidrug resistance behavior. The resulting PLA + OTOA films could be used in a variety of biomedical and packaging applications, including wound dressings and antibacterial food packaging.