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.

Self-Setting Calcium Orthophosphate Formulations: Cements, Concretes, Pastes and Putties

“…For example, crystals of mannitol, CH 2 OH(CHOH) 4 CH 2 OH, were tested as an air-entraining agent; however, both loss of workability during the cement mixing and severe depreciation of mechanical properties were discovered simultaneously [296][297][298][299][300][301]. Other porogenic agents (e.g., oxygen peroxide [302] in the liquid phase and/or iced [303], sucrose granules, NaHCO 3 and Na 2 HPO 4 crystals of 125 -250 µm in size [304], poly(D,L-lactic-co-glycolic acid) microparticles with the average size of 66 ± 25 µm [305][306][307][308][309][310], pectin microspheres [311], calcium sulfate [46], calcite [219], NaCl crystals varying in size from 420 μm to 1 mm [312,313], gelatin microspheres [314,315], vesicants [316], cetyltrimethyl ammonium bromide [317], polytrimethylene carbonate [318], some immiscible liquids) have been also tested to create porosity. These additives could be applied on pre-set cements only, while the solubility degree of the particulates during the setting reaction influences both the content and dimensions of the macroporosity.…”

Changes in the drug release pattern of fresh and set simvastatin-loaded brushite cement

“…Moreover, in several studies [18][19][20][21][22] the conditions used were not indicated. Hence, most studies in the literature disregard the fact that the release pattern may change depending on the time the cement was set for; only Canal et al compared the drug release patterns of cements set for different times (1 h vs 7 days), but this was done on apatitic cements only [10].…”

Effect of hydroxyapatite-containing microspheres embedded into three-dimensional magnesium phosphate scaffolds on the controlled release of lysozyme and in vitro biodegradation

“…20,21 In most cases, the MS-containing composite structures were usually aimed to overcome the conventional limitations of tissue engineering scaffolds, especially poor drug delivery ability. Based on recent publications, it would be feasible to achieve a sustained release of a single biomolecule or sequential delivery of dual bioactive molecules for the tissue engineering application.…”