BINARY ANTIBIOTIC NANOPARTICLES FOR SUSTAINED DRUG RELEASE AND ANTIBACTERIAL ACTION

Abstract

One of the important issues nowadays is the rising antibiotic resistance of bacteria, which is due to their ability to undergo horizontal gene transfer, allowing them to exchange genes, as well as acquire mutations that lead to the development of antibiotic resistance. Unfortunately, the development of novel antibiotcs is an intricate and costly process. However, innovative nanoformulations for delivery of antibiotic and other antimicrobial materials provides a promising avenue for advancement in pharmaceutical research without the need for development of new antibiotics. In the current research, novel binary antibiotic nanoparticles were formulated. The nanoparticles consist of mixed nanocrystals of anionic antibiotic (Cefoperazone) and cationic antiobiotic (Tetracycline) sterically stabilized with a surface active polymer (Poloxamer 407) and further coated with a cationic surfactant (HDTAB). The cationic surface functionality is aimed to produce electrostatic adherence of the particles to the negatively charged bacterial cell walls leading to sustained high local antibiotic concentration. The current approach results in an marked enhancement in antimicrobial efficacy compared to application of the free antibiotics at equivalent overall concentrations. This approach also allows the the binary antibiotic nanoparticles to completely dissolve with time leaving no nanoparticulate matter post use. The antimicrobial efficacy of the particles was evaluated on both Gram negative and Gram positive bacterial strains, Escherichia coli and Staphylococcus aureus. The results showed that the developed particles significantly enhanced antimicrobial action, leading to a substantial reduction in bacterial viability at concentrations ranging from 0.25 mM to 0.125 mM, which is below the concentration at which both antibiotics become ineffective against these bacterial strains. We discovered that the produced binary antibiotic delivery system showed moderate cytotoxicity on HeLa cells due to solubility and transfer of the selected cationic surfactant, hexadecyltrimethylammonium bromide to the cell membranes. Further research needs to be conducted to investigate the use of an alternative cationic coating, such as octadecyltrimethylammonium bromide on the surface of the binary antibiotic particles. Octadecyltrimethylammonium bromide is known to be practically insoluble in water, which may allow for a reduction in cytotoxicity of the coated particles and improve their cytototoxicity profile.