title: Controlled release properties and final macroporosity of a pectin microspheres-calcium phosphate composite bone cement.
abstract: The use of calcium phosphate cements (CPC) is restricted by their lack of macroporosity and poor drug release properties. To overcome these two limitations, incorporating degradable polymer microparticles into CPC is an attractive option, as polymer microparticles could help to control drug release and induce macroporosity after degradation. Although few authors have yet tested synthetic polymers, the potentiality of polysaccharides' assuming this role has never been explored. Low-methoxy amidated pectins (LMAP) constitute valuable candidates because of their biocompatibility and ionic and pH sensitivity. In this study, the potentiality of a LMAP with a degree of esterification (DE) of 30 and a degree of amidation (DA) of 19 was explored. The aim of this study was to explore the influence of LMAP microspheres within the composite on the cement properties, drug release ability and final macroporosity after microspheres degradation. Three LMAP incorporation ratios, 2%, 4% and 6% w/w were tested, and ibuprofen was chosen as the model drug. In comparison with the CPC reference, the resulting composites presented reduced setting times and lowered the mechanical properties, which remained acceptable for an implantation in moderate-stress-bearing locations. Sustained release of ibuprofen was obtained on at least 45days, and release rates were found to be controlled by the LMAP ratio, which modulated drug diffusion. After 4months of degradation study, the resulting CPC appeared macroporous, with a maximum macroporosity of nearly 30% for the highest LMAP incorporation ratio, and interconnectivity between pores could be observed. In conclusion, LMAP appear as interesting candidates to generate macroporous bone cements with tailored release properties and macroporosity by adjusting the pectin content within the composites.
authors.affiliation: Université de Toulouse, CIRIMAT, UPS-INPT-CNRS, Faculté de Pharmacie, 118 Route de Narbonne, 31062 Toulouse Cedex 4, France. girod@cict.fr
authors.forename: S
authors.initials: S
authors.lastname: Girod Fullana
authors.forename: H
authors.initials: H
authors.lastname: Ternet
authors.forename: M
authors.initials: M
authors.lastname: Freche
authors.forename: J L
authors.initials: JL
authors.lastname: Lacout
authors.forename: F
authors.initials: F
authors.lastname: Rodriguez
mesh_terms: D000042:Absorption; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry; D001843:Bone Cements / Q000737:chemistry*; D002130:Calcium Phosphates / Q000737:chemistry*; D003460:Crystallization / Q000379:methods; D003692:Delayed-Action Preparations / Q000737:chemistry; D004058:Diffusion; D004339:Drug Compounding / Q000379:methods; D007052:Ibuprofen / Q000737:chemistry*; D008863:Microspheres; D010368:Pectins / Q000737:chemistry*; D016062:Porosity
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001843:Bone Cements; D002130:Calcium Phosphates; D003692:Delayed-Action Preparations; D010368:Pectins; C020243:calcium phosphate; D007052:Ibuprofen