In Vitro Experimental Research Of Calcium Phosphate Cement And Methotrexate Compounds

Objective:To explore the changes of setting time, mechanical properties and microstructrue of composite of various CPC-MTX, and to provide basic results of the bone filling materials that can suppress recurrence of bone tumors. To develop a novel drug delivery system based on calcium phosphate cement (CPC) with Methotrexate(MTX) as a model drug and to study its drug release test in vitro. Methods:Four MTX mass fractions are tested: 0%(group A), 0.1%(group B), 0.2%(group C),and 0.5%(group D), each group had 16 samples. The pasties of CPC-MTX were put in the prepared modular appliances and made into cylinder composites (diameter 0.8cm, height 1.2cm). To measure the setting time with Gillmore's double needles method; to measure the axial direction compressive strength, transversal compressive strength and diametral tensile strength with CSS-2002 electronic universal experimental machine; to observe the changes of CPC's microstructrue with MTX comparing with conventional CPC without MTX. The results of the four groups were compared with variance analysis. Three MTX mass fraction were tested: 0.1%,0.2%,0.5%,after harden, the pasties of CPC-MTX were put into simulated body fluid at 37°C . The concentration of MTX were tested by high efficiency liquid chromatography at specified time, drawing its drug delivering curve and exploring its drug delivering rule. Results: The average initial time and final time(min.) of A,B,C, D groups are: 22.1,40.5; 22.5,40.8; 23.5,41.4; 24.7,42.3.The setting time of conventional CPC (c-CPC) is prolonged when c-CPC contained increasing concentration of MTX, but the setting times of B, C, D groups all have no significant difference compared with group A (p > 0.05). The average axial, transversal and diametral tensile strength(Mpa) are: 39.99, 35.43, 12.32; 34.53, 33.23, 10.73; 33.94, 32.45,9.65;32.38,30.81,6.63. All indexes of groups B,C have no significant difference compared with group A (p > 0.05), the fraction of group D are significantly lower than group A (p<0.05). Microporous crystal structure of CPC and the diversities of microstructrue of c-CPC containing MTX can be distinctly observed with high resolution SEM. The granules of MTX can be observed to attached on surface or deposited in micropores of CPC without changing the fundamental structure. MTX could be released slowly and stably from the MTX-loaded CPC, there was a significant prophase of drug release and was found to agree with the Higuchi equation. The drug release rate and concentration is concerned with the quantity of MTX and had nothing to do with the thickness and shape of CPC. Conclusions:The microstructrue of c-CPC did not change when containing suitable MTX. There were no significant differences of setting time between the four groups. But significant decreasing of index of 0.5% group can be observed compared with c-CPC, and there were no statistic significance of the other groups. However, the stress-bearing of group D is between cancelled bone and cortical bone and can be used in clinical application. A stable drug delivery system can be developed by loading MTX into CPC and the controlled delivery drug concentration can be attained.The effect of both bone repair and medicational therapy can be attained in clinic with this system.