Construction of Gelatin Microsphere/Magnesium Phosphate Bone Cement Composite Drug Sustained Delivery System

Abstract

Emulsification crosslinking method was applied to prepare drug-loaded gelatin microspheres, of which the particle size was mainly between 100-300 μm. The influence of the crosslinking agent content, drug content and rotation speed on the drug-loading rate and encapsulation efficiency and the influence of the drug content and rotation speed on the microspheres' diameter were analyzed. The drug-loaded gelatin microspheres were deliberately combined with magnesium phosphate cement to produce porous magnesium phosphate composite bone cement with drug slow-release property, and then the changes of porosity of the composite system in the process of microsphere degradation and the drug release characteristics of the composite system in vitro were both explored. Results show that with the increase of glucose concentration, both the drug-loading rate and encapsulation efficiency increase firstly and then decrease, while both the drug content and the drug-loading rate increase and the encapsulation efficiency increases firstly and then decreases. Both the drug-loading rate and encapsulation efficiency decrease with the increase of rotation speed. Comprehensive analysis show that the gelatin microspheres with high drug-loading rate and suitable diameter can be obtained under the condition of rotation speed of 400 r/min, glucose concentration of 0.5 g/mL and the mass ratio of drug to gelatin of 1:2. The drug release characteristics in vitro were studied by immersing the magnesium phosphate cement, which was combined with different proportions of drug-loaded microspheres, into the Tris-HCl buffer solution. Results show that in the early releasing stage of 1-10 h, the drug release rate is rapid and then it obviously slows down. After being released for 7 d, microspheres almost degraded completely and the drug release ratio reaches 60%-89%. Drug slow-release property is achieved to some extent.