Study On Preparation And Physicochemical Properties Of Gelatin Microspheres Loaded With Steroidal Saponins From Ophiopogon Japonicus

Bone defects are common clinical disease.It is the focus and difficulty of bone tissue engineering research.Steroidal saponins facilitate the osteoblastic differentiation by increasing the expression of osteocalcin,alkaline phosphatase and type Ⅰ collagen,thereby promoting osteoinduction and osteointegration of osteoblasts,and promoting the proliferation of osteoblasts by accelerating the cell cycle.However,steroidal saponins have the problems of fast degradation and mismatch with bone repair cycle.The sustained-release technology of drug microsphere provides feasibility for the efficient applications of steroidal saponins.Steroidal saponins and the carrier are combined into a delivery system,which is compounded with bone graft alternative materials,and then gradually releases steroidal saponins in vivo as the carrier degrades,thereby prolonging the action time of steroidal saponins.Based on this,steroidal saponins can be developed into a new dosage form for microspheres used to repair bone defects.In this thesis,biodegradable gelatin was selected as the carrier material,and the emulsion cross-linking method was used to prepare gelatin microspheres loaded with steroidal saponins.The preparation process and formulation optimization of microspheres were discussed,and the physicochemical properties of the microspheres were investigated.The results show that the optimal preparation process was optimized by single-factor test and star point design-effect surface method: the mass ratio of steroid saponins to gelatin was 1:2.169,the emulsion time was 30 min,the emulsion temperature was 40 ℃,the emulsion speed was 824 r/min,the phase volume ratio of water to oil was 1:5,the content of emulsifier was 3.125 ml,and the solidification time was 43 min.The physicochemical properties of the microspheres were investigated.The results showed that the drug loading and encapsulation rate of the microspheres were 35% and 87%,respectively.The gelatin microspheres loaded with steroidal saponins were light yellow powder,and the microspheres showed regular spherical shape with uniform particle size distribution and no adhesion under optical microscope and SEM.FTIR and XRD results indicated that steroidal saponins was successfully encapsulated in the gelatin microspheres.The in vitro release tests showed that the microspheres released about 84% of steroidal saponins within 10 days,which had a certain slow release effect,and the in vitro release of the microspheres was consistent with the first order release kinetic model.Studies on the stability of the microspheres showed that it should not be preserved under high temperature and high humidity,it can be released at normal temperature(25℃)and normally wet(75%).The application of steroidal saponins in bone repair materials has a large theoretical and practical value.Based on the present findings,if more in-depth and detailed studies are conducted,gelatin microspheres loaded with steroidal saponins are expected to become a new dosage form for the treatment of bone defects,which will definitely have good prospects for long-term treatment in bone tissue engineering.