ABSTRACT
The use of 3D scaffolds based on mesoporous bioactive glasses (MBG) enhanced with therapeutic ions, biomolecules and cells is emerging as a strategy to improve bone healing. In this paper, the osteogenic capability of ZnO-enriched MBG scaffolds loaded or not with osteostatin (OST) and human mesenchymal stem cells (MSC) was evaluated after implantation in New Zealand rabbits. Cylindrical meso-macroporous scaffolds with composition (mol %) 82.2SiO2-10.3CaO-3.3P2O5-4.2ZnO (4ZN) were obtained by rapid prototyping and then, coated with gelatin for easy handling and potentiating the release of inorganic ions and OST. Bone defects (7.5 mm diameter, 12 mm depth) were drilled in the distal femoral epiphysis and filled with 4ZN, 4ZN + MSC, 4ZN + OST or 4ZN + MSC + OST materials to evaluate and compare their osteogenic features. Rabbits were sacrificed at 3 months extracting the distal third of bone specimens for necropsy, histological, and microtomography (µCT) evaluations. Systems investigated exhibited bone regeneration capability. Thus, trabecular bone volume density (BV/TV) values obtained from µCT showed that the good bone healing capability of 4ZN was significantly improved by the scaffolds coated with OST and MSC. Our findings in vivo suggest the interest of these MBG complete systems to improve bone repair in the clinical practice.
Subject(s)
Fractures, Bone/therapy , Glass/chemistry , Mesenchymal Stem Cells/cytology , Parathyroid Hormone-Related Protein/chemistry , Peptide Fragments/chemistry , Tissue Scaffolds/chemistry , Zinc Oxide/chemistry , Animals , Biocompatible Materials , Bone Regeneration , Female , Ions , Materials Testing , Osteogenesis , Porosity , Rabbits , X-Ray Microtomography , Zinc/chemistryABSTRACT
Biodegradable scaffolds composed of beta-tricalcium phosphate, and a natural hydrogel, agarose, were prepared by a shaping method based on the thermal gelation of the polymeric component. This technique was modified to facilitate the inclusion, during the scaffold preparation stage, of therapeutic agents that could improve the graft performance. Vancomycin was included in materials containing different amounts of agarose and ceramic without affecting the scaffold consolidation process. These materials, easily injectable, behave like a reinforced hydrogel whose swelling behavior and drug release rate depend on their composition.
Subject(s)
Calcium Phosphates/chemistry , Sepharose/chemistry , Microscopy, Electron, Scanning , Porosity , Sepharose/ultrastructure , Vancomycin/chemistry , Viscosity , X-Ray DiffractionABSTRACT
Mesoporous silica SBA-15 was prepared to evaluate its application as gentamicin drug delivery system. Two procedures were used to evaluate the delivery: calcined powder and disk conformed. The samples were charged with gentamicin sulphate and the experiments were carried out in vitro. No significant difference between powder and disk was observed in the tests. The release profiles exhibited a pronounced initial burst release effect of 60%, followed by a very slow release pattern. A new HPLC method was employed for calculated gentamicin amount in the delivery test. This method requires a small amount of sample, very advisable in these kinds of assays.
Subject(s)
Drug Delivery Systems/methods , Gentamicins/analysis , Chromatography, High Pressure Liquid/methods , Delayed-Action Preparations/administration & dosage , Delayed-Action Preparations/analysis , Delayed-Action Preparations/chemistry , Drug Evaluation, Preclinical/methods , Gentamicins/administration & dosage , Gentamicins/chemistry , Technology, Pharmaceutical/methodsABSTRACT
Cephalexin containing gypsum and apatite/gypsum cements have been synthesised. The presence of cephalexin into the cements does not alter neither the physico-chemical behaviour of the cements nor produce structural changes on them. These cements behave as drug delivery systems when soaked in simulated body fluid. The release of the drug is different depending on the composition. For gypsum cements, the cephalexin is quickly released, helped by a dissolution process of the matrix, whereas the drug release is more controlled by the hydroxyapatite presence in hydroxyapatite/gypsum samples. Apatite containing cements do not only show a different drug release process, also the paste viscosity is lower and a faster formation "in vitro" of an apatite-type layer on their surface is observed.
Subject(s)
Anti-Bacterial Agents/chemistry , Bone Cements/chemistry , Calcium Sulfate/chemistry , Cephalexin/chemistry , Anti-Bacterial Agents/pharmacokinetics , Calorimetry, Differential Scanning , Cephalexin/pharmacokinetics , Microscopy, Electron, Scanning , Spectroscopy, Fourier Transform Infrared , X-Ray DiffractionABSTRACT
In the present paper we present data showing that the effect of the binding of the antitumour drug Pt-pentamidine to nucleosomal DNA is the opposite to that of the cis-DDP compound since it causes strong stabilization of the double helix to heat denaturation and because in nucleosome:Pt-pentamidine complexes the nucleosomal denatured DNA is able to reassociate at 71 degrees C. Upon binding, the pentamidine ligand, by itself, also produces stabilization of the nucleosomal DNA but the effect is lower than that induced by Pt-pentamidine. It seems that in Pt-pentamidine:nucleosome complexes about 50% of the adducts are formed during the first hour of incubation of the nucleosomes with the drug since the increase in Tm of the DNA of these complexes is 53% of the total increase in Tm of the DNA of the Pt-pentamidine:nucleosome complexes formed in 48 h. The 'in vitro' screening of the antiproliferative activity of Pt-pentamidine against 60 tumour cell lines indicated that this antitumour compound shows higher antiproliferative activity against small cell lung, non-small cell lung and melanoma cancer lines than against the rest of the cell lines.
