title: Acrylic injectable and self-curing formulations for the local release of bisphosphonates in bone tissue.
abstract: Two bisphosphonates (BPs), namely 1-hydroxy-2-[4-aminophenyl]ethane-1,1-diphosphonic acid (APBP) and 1-hydroxy-2-[3-indolyl]ethane-1,1-diphosphonic acid (IBP), have been synthesized and incorporated to acrylic injectable and self-curing formulations. Alendronic acid monosodium trihydrated salt (ALN) containing cement was formulated as control. These systems have potential applications in low density hard tissues affected by ailments characterized by a high osteoclastic resorption, i.e. osteoporosis and osteolysis. Values of curing parameters of APBP and IBP were acceptable to obtain pastes with enough fluency to be injected through a biopsy needle into the bone cavity. Working times ranged between 8 and 15 min and maximum temperature was around 50 degrees C. Cured systems stored for a month in synthetic body fluid had compressive strengths between 90 and 96 MPa and modulus between 1.2 and 1.3 GPa, which suggest mechanical stabilization after setting and in the short time. BPs were released in PBS at an initial rate depending on the corresponding chemical structure in the order ALN > APBP > IBP to give final concentrations in PBS of 2.21, 0.44, and 0.19 mol/mL for ALN, APBP, and IBP, respectively. Cytotoxicities of bisphosphonates were evaluated, IC(50) values being in the order APBP > ALN > IBP. Absence of cytotoxicity coming from leachables of the cured systems was observed in all cases independently of the BP. An improved cell growth and proliferation for the systems loaded with APBP and IBP compared with that loaded with ALN was observed, as assessed by measuring cell adhesion and proliferation, and total DNA content.
authors.affiliation: Institute of Polymer Science and Technology, CSIC. C/Juan de la Cierva 3, 28006-Madrid, Spain.
authors.forename: L M
authors.initials: LM
authors.lastname: Rodríguez-Lorenzo
authors.forename: M
authors.initials: M
authors.lastname: Fernández
authors.forename: J
authors.initials: J
authors.lastname: Parra
authors.forename: B
authors.initials: B
authors.lastname: Vázquez
authors.forename: A
authors.initials: A
authors.lastname: López-Bravo
authors.forename: J San
authors.initials: JS
authors.lastname: Román
mesh_terms: D000179:Acrylates / Q000737:chemistry; D000818:Animals; D001843:Bone Cements; D001842:Bone and Bones; D002478:Cells, Cultured; D004247:DNA / Q000032:analysis; D003692:Delayed-Action Preparations; D004164:Diphosphonates / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000633:toxicity; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D007267:Injections; D008422:Materials Testing; D010024:Osteoporosis / Q000188:drug therapy*; D011817:Rabbits
chemical_list: C525211:1-hydroxy-2-(3-indolyl)ethane-1,1-diphosphonic acid; C525210:1-hydroxy-2-(4-aminophenyl)ethane-1,1-diphosphonic acid; D000179:Acrylates; D001843:Bone Cements; D003692:Delayed-Action Preparations; D004164:Diphosphonates; D004247:DNA