Preparation And Drug Controlled Release Properties Of Dual Drug Loaded PMMA-based Composite Bone Cement

Polymethyl methacrylate(PMMA)bone cement is the most commonly used bone cement in clinical practice.It plays an important role in vertebroplasty,bone screw fixation and bone defect filling.It is often added with drugs for local anti-infection and anti-bone adjuvant treatment of osteoporosis.Because antibiotics are generally used in the early postoperative period,and in order to prevent drug resistance,it need to be released quickly,and anti-osteoporosis drugs need to be released for a long time.At present,the conventional drug-loaded bone cement cannot meet the on-demand release of different types of drugs.In response to the above problems,this paper proposes to prepare dual drug loaded gelatin microspheres with a core-shell structure [alendronate sodium(ALN)in the core,gentamicin sulfate(GS)in the shell],and physically blend with PMMA bone cement.By regulating the diameter and content of dual drug loaded gelatin microspheres,the effects of rapid release of antibiotics and sustained release of anti-osteoporosis drugs are achieved.In addition,on this basis,in order to further increase the cumulative release of the drug,ALN and GS were loaded into the interior and surface of the poly(methyl methacrylate-acrylic acid)[P(MMA-AA)]water-absorbing microspheres by dispersion polymerization.Using the water absorption channel formed by compounding with PMMA bone cement to reverse the drug release.The solidification characteristics,mechanical properties,micro-morphology and antibacterial properties of the composite bone cement were characterized,and the drug controlled release mechanism was analyzed.The main research results obtained are as follows:(1)The diameter of the dual drug loaded gelatin microspheres increases with the concentration of the gelatin solution,and the drug encapsulation ratio also increases.The in vitro drug release experiment showed that the dual drug loaded gelatin microspheres/PMMA bone cement achieved the release of GS within 5 weeks,and ALN was released in large quantities from the 4th week and continued to the peak-shaving release behavior of the 10 th week;the addition of dual drug loaded gelatin microspheres improves the setting properties of the composite bone cement,and its mechanical properties meet the needs of use;antibacterial experiments show that the antibacterial properties of the composite bone cement have improved significantly.(2)The diameter of the ALN loaded P(MMA-AA)microspheres decreases as the content of the dispersant polyvinylpyrrolidone(PVP)increases,and the drug encapsulation ratio is above 97%.In vitro drug release experiments show that the dual drug loaded P(MMA-AA)water-swellable bone cement achieves relatively short-term quick release and long-term sustained release of GS and ALN.Compared with dual drug loaded gelatin microspheres/PMMA composite bone cement,The drug release ratio is improved,the release cycle of GS is shortened to 3 weeks,and the release cycle of ALN is extended to 12 weeks.The dual drug loaded P(MMA-AA)water-swellable bone cement has water-absorbable swellable characteristics,its setting characteristics are improved,and the mechanics properties meet the needs of use,and it has good antibacterial properties.