In vitro study and molecular modeling on 17-AAG-loaded polymethyl methacrylate bone cement for multiple myeloma

Abstract

Objective To explore the possibility of polymethyl methacrylate (PMMA) bone cement as the carrier for lipophilic drugs through in vitro cytotoxicity study and molecular modeling with PMMA and 17-allylamino-17-demethoxy-geldanamycin (17-AAG) loaded PMMA bone cement. Methods The 17-AAG loaded bone cement was made by mixing method. In vitro antitumor activity with MTT assay for PMMA, 17-AAG, the 24 h and 48 h released solution of 17-AAG loaded PMMA bone cement were evaluated. Through Material Studio 5.0, the interaction between 17-AAG and PMMA through the model of Amorphous Cell and energy optimization of Forcite was explored. Results The inhibition ratio of MMA for tumor cells is 9.21%± 0.06% with 50 μmol/L. The 24 h released solution of 17-AAG loaded PMMA bone cement (17-AAG∶PMMA=1∶4 000) inhibits the tumor cells 66.15%±0.43% which has a quick released influence on 17-AAG. The inhibition of 24 h released solution of 17-AAG-loaded PMMA bone cement (17-AAG∶PMMA=1∶1 000, 1∶2 000) shows no significance compared with PMMA released solution (P<0.05). The 48 h released solution of 17-AAG-PMMA (17-AAG∶PMMA=1∶1 000, 1∶2 000, 1∶4 000) inhibits U266 30.25%±4.47%, 30.24%±3.42%, 50.52%±5.20%, with a significant difference with PMMA. The molecular model showed that the interaction between 17-AAG and PMMA was van der Waalz bonds, which drove 17-AAG inside or on the surface of PMMA bone cement. Conclusion PMMA bone cement can be used as a carrier for lipophilic drugs. It has antitumor activity and influences the release of 17-AAG with different ratio, for example it has a sustained-released influence on 17-AAG in 17-AAG-PMMA (17-AAG∶PMMA=1∶1 000, 1∶2 000). Molecular model implies that 17-AAG exists inside or on the surface the PMMA bone cement through van der Waalz bonds. Key words: Multiple myeloma; Polymethacrylic acids; In vitro; Molecular mimicry