Encapsulation in emulsion microgels: A high-tech strategy for the rational use of antibiotics

Abstract

Background and Objectives: The search of new effective antibacterial drugs and the development of more advanced dosage and delivery systems for existing antibiotics (AB) are actual research objectives for biomedical science. During the study emulsion microgels (EM), based on whey protein isolate, containing antibacterial drugs (cefazolin (CZ), ceftriaxone (CT)) were obtained by ultrasonic homogenization method. The effect of AB-loaded EM on E. coli strain was studied in comparison to free AB. Materials and Methods: The formation of oil-in-water microemulsions stabilized by whey protein isolate (WPI) in saline was carried out using the method of spontaneous emulsification during ultrasonic homogenization using a rod ultrasonic homogenizer. This approach is based on the denaturation of protein under ultrasonic influence on a solution of biomolecules with the subsequent formation of a microgel shell on the surface of oil droplets. Quantitative characteristics of antibiotics loading and its release from microgels were determined spectrophotometrically. Visualization and calculation of EMs particle sizes were carried out using an optical microscope. The study of AB-loaded EM antibacterial action was performed in liquid nutrient media followed by seeding onto nutrient agar. The experiment was followed with live-dead test, carried out by flow cytometry with cell visualization. Results: The rate and characteristics of AB release from the obtained carriers in various model media, as well as the antimicrobial activity of microgels, have been studied. It has been found that the release of AB from synthesized carriers on the first day of the experiment is 10% in all studied model systems. The total amount of AB released over 144 hours reaches 20% in saline solution and 30% in artificial urine. According to the results of the experiment, all samples of EM, containing CZ caused inhibition of E. coli growth within 7 days. Of these, total suppression of bacterial growth was observed within 1 day for EM 1 : 3 and 1 days for EM 1 : 5, on the remaining days – partial growth suppression. Free CZ remained active during the first day. EM, containing CT, demonstrated an antibacterial effect for 14 days. In this case, the bactericidal nature of the action was observed within 10 days for EM 1 : 3 and 13 days for EM 1 : 5. Free CT also had an antimicrobial effect for 14 days, but the duration of the period of complete growth inhibition in all control samples was significantly shorter compared to EM samples. Conclusion: The immobilization of antibacterial drugs (CZ, CT) into emulsion microgels not only does not lead to a decrease in their effectiveness, but also makes it possible to significantly increase the duration and intensity of action of these drugs. The results obtained are of interest for further study of the possibilities of using emulsion MGs based on WMB as carriers of antibacterial drugs.

Keywords

• antibiotics
• cephalosporins
• emulsion microgels
• whey protein isolate