Abstract
In this work, novel polymeric mixed micelles from Pluronic F127 and Cremophor EL were investigated as drug delivery systems for Norfloxacin as model antibiotic drug. The optimal molar ratio of surfactants was determined, in order to decrease critical micellar concentration (CMC) and prepare carriers with minimal surfactant concentrations. The particle size, zeta potential, and encapsulation efficiency were determined for both pure and mixed micelles with selected composition. In vitro release kinetics of Norfloxacin from micelles show that the composition of surfactant mixture generates tunable extended release. The mixed micelles exhibit good biocompatibility against normal fibroblasts MRC-5 cells, while some cytotoxicity was found in all micellar systems at high concentrations. The influence of the surfactant components in the carrier on the antibacterial properties of Norfloxacin was investigated. The drug loaded mixed micellar formulation exhibit good activity against clinical isolated strains, compared with the CLSI recommended standard strains (Staphylococcus aureus ATCC 25923, Enterococcus faecalis ATCC 29213, Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 25922). P. aeruginosa 5399 clinical strain shows low sensitivity to Norfloxacin in all tested micelle systems. The results suggest that Cremophor EL-Pluronic F127 mixed micelles can be considered as novel controlled release delivery systems for hydrophobic antimicrobial drugs.
Highlights
The adequate composition of the mixed polymeric micelles to ensure the minimum content of surfactants and a low value of critical micellar concentration (CMC) was evaluated from the non-ideal behavior of surfactant mixture, using Rubingh model
The self-assembling properties of the aqueous solution of Cremophor EL and Pluronic F127 have been studied and CMC values were calculated from the variation of pyrene fluorescence spectra, i.e, variation of the I3/I1 ratio with concentration of surfactant, as described in the previous section
F127 show lack of cytotoxicity up to no change in cell viability was measured for sample even at concen1.5 × 10 M, as it is reported in most paper for low concentrated polymeric solutions tration 8approximative times higherregion the CMC, decrease was noticed fordecrease the 3.2 ×
Summary
Infectious disease treatments continue to impose the extensive use of antibiotics. Despite the remarkable advances made in the last century in the synthesis of new drugs with antimicrobial activity, there are many deficiencies, such as high toxicity, low solubility, reduced bioavailability, and inadequate release profile for both new and old antibiotics successfully used in the present therapies. The main issue, remains the multidrug resistance, which produce a huge burden on the global health system. To overcome these drawbacks, in the last decades, nanosized drug delivery systems have been generate increasing interest of the scientific community, due to their unique 4.0/).
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