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Liposomes loaded with rifampicin and tobromycin for anti-Staphylococcus aureus action

M.N. DeSilva, W.W. Zhao, S.T. Schultz, K. Whang, L. Chu
Naval Medical Research Unit San Antonio, US

Keywords: liposomes, multi drug resistant bacteria, antibiotics, antibacterial activities


Reducing patient recovery time and potential post surgical complications of warfighters after traumatic injury is of importance for the military. However, a current medical challenge in treating warfighters with traumatic injuries is bacterial infection due to multi-drug resistant bacteria. These infections can delay wound healing and increase the rate of mortality in severe cases of infections. We are developing a nanosystem for preserving functionality and controlling delivery of antibiotics for an extended period of time which exerts antibacterial activities for a broad spectrum of bacterial species. In this study, we investigated the efficiency of entrapping two antibiotics, rifampicin and tobramycin, [active against Staphylococcus aureus (Sa, ATCC 12600) and Methicillinresistant strain of Sa (MRSA, BAA-1720)] in liposomes synthesized by a modified dehydration-rehydration liposome method for preserving and controlling delivery of antibiotics. The particle size, entrapment efficiency, and antibacterial activities were determined. Encapsulation efficiency of liposomes decreased with decrease in drug concentration. For rifampicin, initial drug loadings of 40 mg, 20 mg and 10 mg resulted in entrapment efficiencies of 64.8 ± 17.3%, 49.6 ± 1.9, and 39.2 ± 9.7%, respectively, and for tobramycin they were 26.7 ± 4.7%, 24.3 ± 5.3% and 22.5 ± 3.5%, respectively. The type of drug also affected encapsulation efficiency. The average particle sizes of liposomes in the mixture was approximately 200-300 nm and 300-500 nm for tobramycin and rifampicin, respectively, and they also varied depending on the amount of drug that was used for liposome synthesis. In vitro antibiotic release studies were performed for 7- 9 days in phosphate-buffered saline (PBS) at 37°C. The results demonstrated that liposomes released sufficient amount of antibiotics, and antibacterial activities were maintained over this period against Sa while preserving the antibiotic functionality. Currently, we are investigating a variety of ways to incorporate these liposome systems into various antimicrobial agent delivery systems.
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