Optimization of particle size and encapsulation efficiency of vancomycin nanoparticles by response surface methodology.

Treating vancomycin-resistant Staphylococcus aureus strains requires high doses of vancomycin, which might lead to adverse reactions such as nephrotoxicity and "red neck syndrome". Use of nanotechnology for antibiotic delivery is a promising approach to overcome antibiotic-resistance. The objective of this study was optimizing the particle size and encapsulation efficiency (EE) of vancomycin nanoparticles prepared from chitosan. The nanoparticles were prepared by ionotropic gelation method, at different combinations of chitosan concentration, chitosan/tripolyphosphate mass and vancomycin/chitosan mass, using Box-Behnken experimental design. Dynamic light scattering and ultracentrifugation were used to measure the nanoparticle size and EE, respectively. Vancomycin was quantified in samples by spectrophotometery. The optimum conditions were determined by subsequent regression analysis and multicriteria decision analysis of the output data. The nanoparticle size and EE were greatly influenced by the independent variables, which had interactive effects on both responses. The optimum conditions for production of nanoparticles were chitosan concentration of 0.5-1.2 mg/ml, chitosan/tripolyphosphate mass ratio of 3-3.5 and vancomycin/chitosan mass ratio of 1, which yielded nanoparticles between 130 and 150 nm with encapsulation efficiencies of 60-69%. The size and EE of vancomycin nanoparticles were optimized by the proposed procedure.