Carmen Rueda

Loading and release of doxycycline hyclate from strontium-substituted calcium phosphate cement

Novel Sr-substituted calcium phosphate cement (CPC) loaded with doxycycline hyclate (DOXY-h) was employed to elucidate the effect of strontium substitution on antibiotic delivery. The cement was prepared using as reactants Sr-substituted beta-tricalcium phosphate (Sr-beta-TCP) and acidic monocalcium phosphate monohydrate. Two different methods were used to load DOXY-h: (i) the adsorption on CPC by incubating the set cement in drug-containing solutions; and (ii) the use of antibiotic solution as the cement liquid phase. The results revealed that the Sr-substituted cement efficiently adsorbs the antibiotic, which is attributed to an enhanced accessibility to the drug-binding sites within this CPC. DOXY-h desorption is influenced by the initial adsorbed amount and the cement matrix type. Furthermore, the fraction of drug released from CPCs set with DOXY-h solution was higher, and the release rate was faster for the CPC prepared with 26.7% Sr-beta-TCP. The analysis of releasing profiles points to Fickian diffusion as the mechanism responsible for antibiotic delivery. We can conclude that Sr substitution in secondary calcium phosphate cements improves their efficiency for DOXY-h adsorption and release. The antibiotic loading method provides a way to switch from rapid and complete to slower and prolonged drug release.

Effect of silica gel on the cohesion, properties and biological performance of brushite cement

The cohesion of calcium phosphate cements can be improved by the addition of substances to either the solid or liquid phase during the setting reaction. This study reports the effect of silica gel on brushite cement cohesion. The cement was prepared using a mixture of beta-tricalcium phosphate (beta-TCP) and monocalcium phosphate monohydrate as the solid phase, while the liquid phase comprised carboxylic acids silica gel. This cement presents a shorter final setting time (FST), better cohesion and higher amount of unreacted beta-TCP than the cement prepared without silica gel. Furthermore, in vivo experiments using rabbits as an animal model showed that after 8 weeks of implantation cements modified with silica gel showed a similar new bone formation volume and more remaining graft in comparison with unmodified cements. Thus, the silica gel could be efficiently applied to reduce cement disintegration and to decrease the resorption rate of brushite cements.

The effect of hyaluronic acid on brushite cement cohesion

The improvement of calcium phosphate cement (CPC) cohesion is essential for its application in highly blood perfused regions. This study reports the effectiveness of hyaluronic acids of different molecular weights in the enhancement of brushite cement cohesion. The cement was prepared using a powder phase composed of a mixture of beta-tricalcium phosphate and monocalcium phosphate monohydrate, whereas the liquid phase was formed by 0.5M citric acid solution modified by the addition of hyaluronic acid of different molecular weights. It was found that medium and high molecular weight hyaluronic acid enhances the cement cohesion and scarcely affects the cement mechanical properties. However, concentrations >0.5% (w/v) were less efficient to prevent the cement disintegration. It is concluded that hyaluronic acid could be applied efficiently to reduce brushite cement disintegration.

Magnesium substitution in brushite cements for enhanced bone tissue regeneration.

We have synthesized calcium phosphate cements doped with different amounts of magnesium (Mg-CPC) with a twofold purpose: i) to evaluate in vitro the osteoblast cell response to this material, and ii) to compare the bone regeneration capacity of the doped material with a calcium cement prepared without magnesium (CPC). Cell proliferation and in vivo response increased in the Mg-CPCs in comparison with CPC. The Mg-CPCs have promoted higher new bone formation than the CPC (p<0.05). The cytocompatibility and histomorfometric analysis performed in the rabbit calvaria showed that the incorporation of magnesium ions in CPC improves osteoblasts proliferation and provides higher new bone formation. The development of a bone substitute with controllable biodegradable properties and improved bone regeneration can be considered a step toward personalized therapy that can adapt to patient needs and clinical situations.

Effect of physicochemical properties of a cement based on silicocarnotite/calcium silicate on in vitro cell adhesion and in vivo cement degradation

A silicon calcium phosphate cement (Si-CPC) was developed to produce a composite of calcium phosphate and calcium silicate. The silicon cements prepared with low silicon (Si) content were composed of crystalline phases of brushite and silicocarnotite. However, the cements prepared with high Si content were mainly composed of amorphous phases of silicocarnotite, hydroxyapatite and calcium silicate. The cement porosity was about 40% with a shift of the average pore diameter to the nanometric range with increasing Si content. Interestingly, this new cement system provides a matrix with a high specific surface area of up to 29 m(2) g(-1). The cytocompatibility of the new Si-doped cements was tested with a human osteoblast-like cell line (MG-63) showing an enhancement of cell proliferation (up to threefold) when compared with unsubstituted material. Cements with a high silica content also improved the cell attachment. The in vivo results indicated that Si-CPCs induce the formation of new bone tissue, and modify cement resorption. We conclude that this cement provides an optimal environment to enhance osteoblast growth and proliferation that could be of interest in bone engineering.

Changes in the flow properties of phospholipid dispersions induced by procaine hydrochloride. Effect of pH and temperature.

Since local anaesthetics are known to interact with membrane lipids, we have examined the changes taken place by procaine hydrochloride in lipid matrices as a function of pH. Rheological methods might give useful information on the association of this anaesthetic with soybean lecithin. The procaine interacted with negatively charged phospholipid polar head groups at pH 4. This system exhibits a loosening in the tight arrangement of phospholipid molecules caused by the addition of procaine as a function of this anaesthetics concentration. The flow enthalpy values as a function of procaine-lipid ratio shows biphasic behaviour and suggests a phase transition when the anaesthetic concentration goes from 10 to 14 mM and temperatures dip below 10 degrees C.

Strontium Ions Substitution in Brushite Crystals: The Role of Strontium Chloride

The incorporation of strontium chloride to brushite cement was successful to introduce strontium ions within the lattice of brushite crystals. The effect of strontium ions on brushite cement properties was concentration dependent; such that, the addition of 5% and 10% (w/w) SrCl2 significantly increased the cement FST and the addition of 10% SrCl2 decreased the cement tensile strength. Further, cement weight loss was shown to be increased by cement modification with SrCl2. The combination of ionic substitution and the degradability of brushite cements would constitute a system for the local delivery of strontium ions in the treatment of osteoporosis.

Mucopolysaccharides in aqueous solutions: effect of ionic strength on titration curves☆

We study the changes taking place in hyaluronic acid, chondroitin 4-sulfate (C4-S) and condroitin 6-sulfate (C6-S), at ionic strengths of 0.10, 0.15, and 0.20 in NaCl, in a neutralization process in aqueous solution. We apply the equation of Henderson Hasselbalch modified for polyelectrolytes and evaluate the changes in the electrostatic free energy starting from the pK curves as a function of the dissociation degree. For a dissociation degree next to 0.4 corresponding to the -COOH group of the hyaluronic acid, we observed a change in the conformation of the three glycosaminoglycans studied. This conformational change takes place as a consequence of the break of intramolecular links and the beginning of the ionization process. The macromolecules in solution show a structure of random coil sufficiently expanded so that the interaction among the close ionizable groups is negligible.

Development of tutorial videos to guide students of pharmacy and optics and optometry to achieve academic abilities

11th International Technology, Education and Development Conference, Valencia, Spain, 6-8 March, 2017