title: Method for the physical analysis of drug-bone cement composite.
abstract: Skeletal metastases are often complicated by progression to impending or pathologic fracture and fixation with polymethylmethacrylate (PMMA) bone cement is used for stabilization and pain relief. Adjuvant therapy involving the delivery of PMMA composites mixed with antibiotic or chemotherapeutic agents requires an understanding of the rate of drug diffusion from the cement in addition to measurement of its mechanical properties pre- and postelution of drug. We have developed a method for the analysis of drug diffusion rate and mechanical properties of drug-cement composites using PMMA/methotrexate as a model system. The analysis method revealed the addition of methotrexate to PMMA in concentrations of 1.8 g methotrexate per 40 g PMMA did not change the compression modulus of the cement pre- or postelution of drug. The PMMA/methotrexate composites displayed an average diffusion rate of 50 ng/(mm2)(hour) during the first 6 hours, which decreased to 10 ng/(mm2)(hour) by 36 hours. Diffusion modeling predicts the 20 x 13-mm cylindrical PMMA/methotrexate samples used by the method deliver 10% of the total methotrexate content within 80 hours and 25% of the total within 133 days.
authors.affiliation: Department of Orthopaedic Surgery, Albert Einstein Medical Center, Philadelphia, PA 19141, USA. handalj@einstein.edu
authors.forename: John A
authors.initials: JA
authors.lastname: Handal
authors.forename: Richard F
authors.initials: RF
authors.lastname: Frisch
authors.forename: William L
authors.initials: WL
authors.lastname: Weaver
authors.forename: Eric A
authors.initials: EA
authors.lastname: Williams
authors.forename: Darlise
authors.initials: D
authors.lastname: Dimatteo
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D001843:Bone Cements; D019245:Compressive Strength; D004058:Diffusion; D004337:Drug Carriers; D006801:Humans; D008422:Materials Testing / Q000379:methods*; D008727:Methotrexate / Q000008:administration & dosage*; D008768:Methylmethacrylates
chemical_list: D000964:Antimetabolites, Antineoplastic; D001843:Bone Cements; D004337:Drug Carriers; D008768:Methylmethacrylates; C506662:vertebroplastic; D008727:Methotrexate