Study On Calcium Phosphate Cement Loading Anti-TB Drug

ObjectiveTo develop a novel anti-TB porous calcium phosphate cements composite by incorporating the Rifampicin-loaded poly(lactic-co-glycolic acid) microspheres (RFP-PLGA Ms) and to evaluated the performance of the composite as a bone substitute in vitro and in vivo.MethodsThe biodegradable Rifampicin-loaded poly(lactic-co-glycolic acid) microspheres were prepared from poly(lactic-co-glycolic acid) using a double-emulsion solvent-extraction [(water-in-oil)-in-water] technique to encapsulate rifampicin. Drug-carried rate,envelopment rate and the characteristics of drug release in vitro were characterized. RFP-PLGA Ms were mixed with an calcium phosphate cement at there different weight ratios (10%,20%,30%) to generate an anti-TB drug delivery system.The porosity and the compression strength of the three composites were measureed to determine the proper weight ratio of RFP-PLGA Ms. The Wistar rat bone marrow stromal stem cells (rBMSCs) were also cultured with different leaching liquor of three kinds of materials (20% RFP-PLGA Ms/CPC, RFP/CPC,CPC). Cell viability analysis was performed by MTT assay, and alkaline phosphates was measured with alkaine phosphatase kit, and estimated cytotoxicity of materials. At 2.4. 8.12 weeks after implanted in the rabbit's femoral condyle,the muscles beside the femoral condyle were obtained and RFP in the muscles were measured by high performance liquid chromatography(HPLC). At 12 weeks the samples with the materials were obtained and evaluated by pathological anatomy.ResultsFor the 10%.20%.30% of RFP-PLGA/CPC composites, the total porosity, large porosity and compressive strength were (54.76±1.31)%,(13.67±1.62)%,(11.89±0.96)Mpa;(63.76±1.35)%,(23.87±1.67)%,(4.8±0.68) Mpa; (72.97±1.10)%,(37.87±2.08)%,(1.03±0.65) Mpa, respectively. RFP release in RFP-PLGA/CPC group was better than in RFP/CPC group (P<0.05), and the former maintained the RFP level at the minimum inhibitory concentration (MIC) over 10 times for a longer period. At 12 weeks RFP-PLGA/CPC were implanted, and the degradation of RFP-PLGA/CPC was significantly faster than in the control group. The former of bone ingrowth rate was (34.56±1.47)%, significantly higher than (1.56±0.84)% (P<0.05).ConclusionsRFP-PLGA Ms can significantly increase the porosity of CPC and promote its degradation. RFP can release for a long time and maintain an effective local anti-tuberculosis drug concentration, thus reducing the recurrence rate of bone tuberculosis. It can be used to repair tubercular skeletal defect.