Abstract: BACKGROUND: At present, the most common choice for treatment of bone joint tuberculosis is oral and systemic anti-tuberculosis drugs, but drug-resistant tuberculosis strains and drug side effects are prone to occur, and the local drug concentration is low at the lesion. Biodegradable microspheres buried in the lesions can be given at a specific point, delay drug release and control the rate of release, providing a new treatment for the treatment of bone joint tuberculosis.
OBJECTIVE: To design orthogonal experiments to optimize the preparation process parameters of rifampicin-loaded silk fibroin microspheres, and prepare sustained-release microspheres with round morphology, uniform particle size, high drug loading and encapsulation rates, and to explore the release behavior of the microsphere in vitro drug experiment.
METHODS: Using silk fibroin solution as the water phase, liquid paraffin as the oil phase, and Span-80 as the emulsifier, the silk fibroin drug-loaded microspheres loaded with rifampicin were prepared by the emulsification solvent positive method. Orthogonal experiment was designed to investigate stirring speed (300, 500, 700, 900 r/min), isopropanol and silk fibroin solution volume ratio (1:1, 2:1, 4:1, 6:1), water-oil volume ratio (1:6, 1:8, 1:10, 1:12), emulsifier content (2%, 4%, 6%, 8%) and temperature (25, 35, 45, 55 °C) influences on the morphology, drug loading rate and encapsulation rate of drug-loaded microspheres. 
RESULTS AND CONCLUSION: Orthogonal experiment results showed that the best process parameters were the stirring speed of 900 r/min, the volume ratio of isopropanol to silk fibroin solution of 1:1, the volume ratio of water to oil of 1:6, the Span-80 concentration of 2%, and the temperature of 55 °C. Under this condition to make silk fibroin microspheres, the surface of the microsphere was smooth, with good spherical effect; the microsphere size was about 11.18 µm; drug-loaded rate was 10.56%; encapsulated rate was 42.78%; cumulative release rate of 68.4% in 144 hours. Microsphere is stable and sustained on drug release, and has a good drug release effect.

Key words: material, silk fibroin, microsphere, drug-loaded microsphere, orthogonal experiment, emulsification solvent evaporation method, drug-loaded rate, encapsulation rate, cumulative drug release rate, sustained release