Chitosan-modified ceftazidime loaded polyhydroxyalkanoates microparticles: preparation, characterization and antibacterial evaluation in vitro: Original scientific article

Anastasiya Murueva; Natalia Zhila; Alexey  Dudaev; Ekaterina  Shishatskaya; Tatiana Volova

doi:10.5599/admet.2645

Authors

Anastasiya Murueva Institute of Biophysics SB RAS, Federal Research Center “Krasnoyarsk Science Center SB RAS”, 50/50 Akademgorodok, Krasnoyarsk 660036, Russia and Siberian Federal University, 79 Svobodnyi av., Krasnoyarsk 660041, Russia https://orcid.org/0009-0006-5423-6002
Natalia Zhila Institute of Biophysics SB RAS, Federal Research Center “Krasnoyarsk Science Center SB RAS”, 50/50 Akademgorodok, Krasnoyarsk 660036, Russia and Siberian Federal University, 79 Svobodnyi av., Krasnoyarsk 660041, Russia https://orcid.org/0000-0002-6256-0025
Alexey Dudaev Institute of Biophysics SB RAS, Federal Research Center “Krasnoyarsk Science Center SB RAS”, 50/50 Akademgorodok, Krasnoyarsk 660036, Russia and Siberian Federal University, 79 Svobodnyi av., Krasnoyarsk 660041, Russia https://orcid.org/0000-0003-4873-126X
Ekaterina Shishatskaya Institute of Biophysics SB RAS, Federal Research Center “Krasnoyarsk Science Center SB RAS”, 50/50 Akademgorodok, Krasnoyarsk 660036, Russia and Siberian Federal University, 79 Svobodnyi av., Krasnoyarsk 660041, Russia https://orcid.org/0000-0001-7967-243X
Tatiana Volova Institute of Biophysics SB RAS, Federal Research Center “Krasnoyarsk Science Center SB RAS”, 50/50 Akademgorodok, Krasnoyarsk 660036, Russia and Siberian Federal University, 79 Svobodnyi av., Krasnoyarsk 660041, Russia https://orcid.org/0000-0001-9392-156X

DOI:

https://doi.org/10.5599/admet.2645

Keywords:

degradable polyhydroxyalkanoates, P(3HB), copolymer P(3HB-3HV-3HHх);, solvent evaporation, structure and properties, ; antibacterial drug, release kinetics, hemolysis;, keratinocyte proliferation

Abstract

Background and purpose: The use of drug delivery systems to enhance the efficacy of existing antimicrobial drugs is one of the promising approaches to combat bacterial resistance. The simultaneous presence of a polycationic biopolymer (chitosan) and an antibacterial drug (ceftazidime) in polyhydroxyalkanoates microparticles is more effective since it allows such carriers to have a more pronounced therapeutic effect. In this study, chitosan-modified ceftazidime-loaded poly(3-hydroxybutyrate-3-hydroxyvalerate-3-hydroxy-hexanoate) (P(3HB-3HV-3HHх)) microparticles were prepared and investigated as a drug delivery system. Experimental approach: The obtained microparticles were characterized in terms of their particle size, polydispersity index (PDI), zeta potential, encapsulation efficiency, drug release studies in vitro, cytotoxicity and antibacterial properties in cell cultures. Key results: The microparticles had spherical shapes with diameters from 0.6 to 1.6 µm. The constructed chitosan-modified ceftazidime-loaded microparticles 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. In vitro cell viability and proliferation studies on designed microparticles investigated using HaCaT (human keratinocyte skin cell lines) showed good cell proliferation. The hemolytic activity of chitosan-modified P(3HB- 3HV-3HHх) microparticles evaluated by hemolysis assay demonstrated good blood compatibility. Chitosan-modified microparticles enhanced the antibacterial activity of ceftazidime, being effective against E. coli and St. aureus. Conclusion: Thus, the obtained drug delivery systems based on PHAs and chitosan in the form of microparticles can be promising means in treating infectious skin diseases for topical use.

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