Orthogonal optimization of vancomycin/poly(lactic-co-glycolic acid) microspheres: preparation and drug release in vitro

doi:10.3969/j.issn.2095-4344.1509

Abstract

Abstract:

BACKGROUND: Despite the advances in modern antibiotics and surgical techniques, the long-term systemic use of antibiotics for deep soft tissue infections or bone infections, especially methicillin-resistant Staphylococcus aureus infections, is susceptible to nephrotoxicity, ototoxicity and toxic and side effects on the gastrointestinal tract. Moreover, it is expensive and its efficacy is uncertain. The local drug delivery system can achieve sustained-release of high concentrations of antibiotics in the local infection, thereby more effectively controlling and treating infections, and significantly reducing the side effects of systemic antibiotic treatment. Vancomycin is encapsulated into poly(lactic-co-glycolic acid) copolymer microspheres carrying vancomycin are gradually degraded and absorbed in the body, and the effective inhibitory concentration of vancomycin can be maintained for a long time at the infection site to achieve local anti-infection effects.

OBJECTIVE: To optimize the preparation process of vancomycin/poly(lactic-co-glycolic acid) microspheres by orthogonal design experiments, then to prepare the vancomycin/poly(lactic-co-glycolic acid) sustained-release microspheres with uniform particle size, and to test their drug release and antibacterial properties in vitro at the same time.

METHODS: Using double-emulsion solvent evaporation method, taking the drug loading rate and entrapment efficiency of microspheres as the main indicators, the orthogonal experiments of four factors and three levels were carried out under four different process conditions, including the concentration of poly(lactic-co-glycolic acid) solution, the concentration of internal water phase, the polyvinyl alcohol concentration of external water phase and the speed of agitation.

RESULTS AND CONCLUSION: The optimum conditions were as follows: oil phase 9 mL: poly(lactic-co-glycolic acid) 500 mg, internal water phase 1 mL vancomycin 300 mg, external water phase: polyvinyl alcohol concentration was 3%, the speed: 400 r/min. When the other three factors were unchanged and the stirring rate was 400, 800 and 1 200 r/min, the microspheres with the particle size of (232±26), (157±23), (102±37) µm were prepared. For the microspheres with an average particle size of (102±37) µm, the drug loading rate was (17.40±1.87)% and the entrapment efficiency was (35.12±3.65)%. The drug release in vitro showed that the release rate of the microspheres on the 1^st day was (17.91±2.41)%, and there was a certain burst of release. After 2 days, the release rate gradually decreased and slowed down, the cumulative release was (58.78±1.54)% at the 12^th day, the average daily release was 1.41% from the 12^th to the 24^th day, and the total release was (75.31±1.02)% at the 24^th day. These findings indicate that using the optimal preparation process, we can prepare vancomycin/ poly(lactic-co-glycolic acid) sustained-release microspheres with uniform particle size and smooth drug release.

中国组织工程研究杂志出版内容重点：生物材料；骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性；组织工程

Key words: Vancomycin Resistance, Microspheres, Tissue Engineering

CLC Number:

R452

R313

Liu Yazhen, Qiu Xiaoming, Li Songkai. Orthogonal optimization of vancomycin/poly(lactic-co-glycolic acid) microspheres: preparation and drug release in vitro[J]. Chinese Journal of Tissue Engineering Research, 2019, 23(2): 211-217.

Figures/Tables 7

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