Ulrika Brohede

Mesoporous silica-based nanomaterials for drug delivery: evaluation of structural properties associated with release rate.

We present here a study of the controlled release of amino acid-derived amphiphilic molecules from the internal pore structure of mesoporous nanoparticle drug delivery systems with different structural properties, namely cubic and hexagonal structures of various degrees of complexity. The internal pore surface of the nanomaterials presented has been functionalised with amine moieties through a one-pot method. Release profiles obtained by conductivity measurements are interpreted in terms of specific structural and textural parameters of the porous nanoparticles, such as pore geometry and connectivity. Results indicate that diffusion coefficients are lower by as much 4 orders of magnitude in two-dimensional structures in comparison to three-dimensional mesoporous solids. A fast release in turn is observed from mesocaged materials AMS-9 and AMS-8, where the presence of structural defects is thought to lead to a slightly lower diffusion coefficient in the latter. We conclude that the use of single or mixed phases of these porous systems can be utilized to provide sustained release over long time periods and expect their use in a variety of formulations.

In vitro characterization of bioactive titanium dioxide/hydroxyapatite surfaces functionalized with BMP-2

Poor implant fixation and bone resorption are two of the major challenges in modern orthopedics and are caused by poor bone/implant integration. In this work, bioactive crystalline titanium dioxide (TiO(2))/hydroxyapatite (HA) surfaces, functionalized with bone morphogenetic protein 2 (BMP-2), were evaluated as potential implant coatings for improved osseointegration. The outer layer consisted of HA, which is known to be osteoconductive, and may promote improved initial bone attachment when functionalized with active molecules such as BMP-2 in a soaking process. The inner layer of crystalline TiO(2) is bioactive and ensures long-term fixation of the implant, once the hydroxyapatite has been resorbed. The in vitro response of mesenchymal stem cells on bioactive crystalline TiO(2)/HA surfaces functionalized with BMP-2 was examined and compared with the cell behavior on nonfunctionalized HA layers, crystalline TiO(2) surfaces, and native titanium oxide surfaces. The crystalline TiO(2) and the HA surfaces showed to be more favorable than the native titanium oxide surface in terms of cell viability and cell morphology as well as initial cell differentiation. Furthermore, cell differentiation on BMP-2-functionalized HA surfaces was found to be significantly higher than on the other surfaces indicating that the simple soaking process can be used for incorporating active molecules, promoting fast bone osseointegration to HA layers.

Bone response to a novel Ti–Ta–Nb–Zr alloy

Commercially pure titanium (cp-Ti) is regarded as the state-of-the-art material for bone-anchored dental devices, whereas the mechanically stronger alloy (Ti-6Al-4V), made of titanium, aluminum (Al) and vanadium (V), is regarded as the material of choice for high-load applications. There is a call for the development of new alloys, not only to eliminate the potential toxic effect of Al and V but also to meet the challenges imposed on dental and maxillofacial reconstructive devices, for example. The present work evaluates a novel, dual-stage, acid-etched, Ti-Ta-Nb-Zr alloy implant, consisting of elements that create low toxicity, with the potential to promote osseointegration in vivo. The alloy implants (denoted Ti-Ta-Nb-Zr) were evaluated after 7 days and 28 days in a rat tibia model, with reference to commercially pure titanium grade 4 (denoted Ti). Analyses were performed with respect to removal torque, histomorphometry and gene expression. The Ti-Ta-Nb-Zr showed a significant increase in implant stability over time in contrast to the Ti. Further, the histological and gene expression analyses suggested faster healing around the Ti-Ta-Nb-Zr, as judged by the enhanced remodeling, and mineralization, of the early-formed woven bone and the multiple positive correlations between genes denoting inflammation, bone formation and remodeling. Based on the present experiments, it is concluded that the Ti-Ta-Nb-Zr alloy becomes osseointegrated to at least a similar degree to that of pure titanium implants. This alloy is therefore emerging as a novel implant material for clinical evaluation.

Sustained Release from Mesoporous Nanoparticles: Evaluation of Structural Properties Associated with Release Rate

We present here a detailed study of the controlled release of amino acid derived amphiphilic molecules from the internal pore structure of mesoporous nanoparticle drug delivery systems with different structural properties; namely cubic and hexagonal structures of various degrees of complexity. The internal pore surface of the nanomaterials presented has been functionalised with amine moieties through a one pot method. Release profiles obtained by Alternating Ionic Current measurements are interpreted in terms of specific structural and textural parameters of the porous nanoparticles such as pore geometry and connectivity. Results indicate that diffusion coefficients are lower by as much as four orders of magnitude in 2-dimensional structures in comparison to 3-dimensional mesoporous solids. A fast release in turn is observed from mesocaged materials AMS-9 and AMS-8 where the presence of structural defects is thought to lead to a slightly lower diffusion coefficient in the latter. Amount of pore wall functionalisation and number of binding sites on the model drug are found to have little effect on the drug release rate.

Proton Absorption in As-Synthesized Mesoporous Silica Nanoparticles as a Structure-Function Relationship Probing Mechanism

A new method to investigate the effect of pore geometry on diffusion processes in mesoporous silica nanoparticles and other types of micro- and mesoporous structures is put forward. The method is based on the study of proton diffusion from a liquid surrounding the mesoporous particles into the particle pore system. The proton diffusion properties are assessed for a variety of as-synthesized mesoporous nano- and microparticles with two-dimensional and three-dimensional connectivity. Results show that the diffusion coefficients are higher for the proton absorption process than for the release of surfactant template molecules, and that they overall follow the same trend with the more complex three-dimensional mesocaged particles showing the highest diffusion coefficients. The pore geometry (cylindrical pores versus cage-type pores) and structure connectivity are found to play a key role for the effects observed. The results put forward in the present work should offer a valuable tool in the development of porous nanomaterials in a range of applications including the use as catalysis and separation enhancers in the petrochemical industry, as scaffolds for hydrogen storage, and as drug delivery vehicles for sustained release and gene transfection.

Fast Loading, Slow Release – A New Strategy for Incorporating Antibiotics to Hydroxyapatite

The aim of this study was to investigate if it is possible to fast load hydroxyapatite with antibiotics and still obtain a slow but therapeutic release of drugs during several hours. Physical vapour deposition was used to coat commercially pure titanium with a layer of anatase TiO2. On top of this, a layer of hydroxyapatite was deposited using biomimetic precipitation. This hydroxyapatite coating was then soaked in solutions containing antibiotics for various amounts of times. The release rate of the antibiotics was measured in PBS during 22 hours. The released amount was compared with the results from an antimicrobial susceptibility test and proved to be sufficient to kill several ml of bacterial broth during the time of the release measurements. It was shown that the soaking time does not affect the release rate and the results suggest that it is possible to develop implants with the option to add antibiotics to their surface at the site of surgery by a simple soaking method.

Percolating ion transport in binary mixtures with high dielectric loss

Percolating ion transport in binary mixtures with high dielectric loss: Dry dielectric spectroscopy recordings and wet time-dependent salt release measurements.

Targeted Local Delivery of Bisphosphonate From Orthopaedic Implants

Two methods of loading bisphosphonate (BP) into hydroxylapatite (HA) coatings on crystalline TiO2 surfaces were investigated to improve bone ingrowth to implant surfaces. In the study the BP pamidronate was used. Ti-plates coated with crystalline TiO2 were soaked in phosphate buffer saline (PBS) for 7 days at 40° C and thereafter soaked in solutions of BP, 0.5 mg/ml for 15 or 60 minutes (fast loading method). In the second method BP was dissolved into PBS in different concentrations before immersion of the discs for 7 days (co-precipitation method). Surface and bulk were analysed using electron spectroscopy for chemical analysis, scanning electron microscope and x-ray diffraction. Release of BP was studied using alternating ionic current method. It was shown that fast loading by soaking in a BP solution for 15 minutes was sufficient to load BP into a HA coating. Co-precipitation showed that a thin layer of calcium phosphate crystals containing BP can be deposited directly onto a crystalline TiO2 surface.