Drug delivery systems in the form of biodegradable nanoparticles are becoming increasingly important in medicine. Among the representatives of the polyhydroxyalkanoate family, the most promising for use in biomedicine are copolymers of 3-hydroxybutyric acid with inclusions of 4 HB, 3HV or 3HHx monomers. In this regard, the aim of this work was to obtain a three-component copolymer P(3HB-co-3HV-co-3HHx) using Cupriavidus necator B-10646 and to design nanoparticles on its basis, including those loaded with the antibacterial drug ceftazidime.

P(3HB-co-3HV-co-3HHx) samples were synthesized by Cupriavidus necator B-10646 using oleic acid as a carbon substrate. P(3HB-co-3HV-co-3HHх) carriers were obtained via the emulsification method, loaded with ceftazidime and then characterized in terms of particle morphology and size, drug encapsulation and release. The safety and therapeutic efficacy of nanoparticles were assessed in NIH 3T3, E. coli and St. aureus cell cultures.

Using the emulsification method by changing the experimental conditions, nanoparticles with an average diameter from 450 to 900 nm and a zeta potential of -15 -21 mV were obtained. The sustained release of the drug was demonstrated over 28 days in PBS. The kinetics of ceftazidime release from P(3HB-co-3HV-co-3HHx) nanoparticles is described by the Higuchi and Korsmeyer–Peppas models, which corresponds to the diffusion mechanism. The developed polymer nanoparticles loaded with ceftazidime have antibacterial activity and suppress the development of St. aureus and E. coli, without negatively affecting the adhesion and proliferation of fibroblast cells. The number of viable NIH 3T3 fibroblasts cultured in the presence of P(3HB-3HV-3HHx) nanoparticles is comparable to the control.

The developed P(3HB-3HV-3HHx) nanoparticles can be recommended as promising carriers for the delivery of antibacterial drugs.

This study was funded by State Assignment of the Ministry of Science and Higher Education of the RF (Project No. FWES-2021-0025).