Francisco Balas

Flexible Porous Metal-Organic Frameworks for a Controlled Drug Delivery

Flexible nanoporous chromium or iron terephtalates (BDC) MIL-53(Cr, Fe) or M(OH)[BDC] have been used as matrices for the adsorption and in vitro drug delivery of Ibuprofen (or alpha- p-isobutylphenylpropionic acid). Both MIL-53(Cr) and MIL-53(Fe) solids adsorb around 20 wt % of Ibuprofen (Ibuprofen/dehydrated MIL-53 molar ratio = 0.22(1)), indicating that the amount of inserted drug does not depend on the metal (Cr, Fe) constitutive of the hybrid framework. Structural and spectroscopic characterizations are provided for the solid filled with Ibuprofen. In each case, the very slow and complete delivery of Ibuprofen was achieved under physiological conditions after 3 weeks with a predictable zero-order kinetics, which highlights the unique properties of flexible hybrid solids for adapting their pore opening to optimize the drug-matrix interactions.

Influence of composition and surface characteristics on the in vitro bioactivity of SiO2−CaO−P2O5−MgO sol-gel glasses

Glasses in the system SiO(2)-CaO-P(2)O(5)-MgO were prepared by the sol-gel method. These glasses featured SiO(2) contents in the range 60-80 mol %, 4 mol % of P(2)O(5), and a CaO/MgO molar ratio of 4. Because of their composition and surface properties, all the glasses showed in vitro bioactivity, as evidenced by the formation of an apatite-like layer on their surface when soaked in an acellular medium with ionic composition similar to human blood plasma. An increase in the CaO content of the glasses also caused an increase in their porosity. Higher porosity facilitated the apatite nucleation on the sample surface during the first days of the in vitro test. On the other hand, those glasses with higher SiO(2) content also showed higher surface area values, as well as higher calcium phosphate layer growth rates. For longer soaking periods, the grown layer was analyzed, revealing a two-phase composition: apatite and whitlockite.

L-Trp adsorption into silica mesoporous materials to promote bone formation

The properties of ordered mesoporous silicas as bioactive materials, able to induce bone-tissue regeneration, have been combined with their abilities to host and release specific biomolecules in a controlled fashion. The possibility of locally deliver peptides and proteins is of great scientific importance because it opens new paths for the design of implantable biomaterials than can promote bone formation where needed. These biomaterials can host such biofactors, and their adsorption can be enhanced by chemically modifying the silica surface, with the aim of encouraging host-guest interaction and, thereby, increasing the loading capacity of the biomaterial matrix. L-Tryptophan (L-Trp) is a hydrophobic amino acid present in the three-dimensional structure of numerous proteins, and it is used here as model system to predict peptide delivery systems. Unmodified, silanol-rich, bioactive SBA-15 ordered mesoporous silica has been found to be incapable of confining L-Trp in its mesopores due to the hydrophobic character of this molecule. Organically modifying SBA-15 with quaternary amines results in approximately two-thirds of the silica surface being functionalized, increases the surface hydrophobicity allowing an increased L-Trp loading, and also induces different release kinetics. The control of the L-Trp release is the first step in controlled and localized protein delivery technologies, and opens novel perspectives for designing bioactive silica-based devices suitable for bone-healing applications.

Surface electrochemistry of mesoporous silicas as a key factor in the design of tailored delivery devices.

The fundamental mechanisms of biologically active molecule adsorption and release from ordered mesoporous silica are discussed in terms of the variation of surface electrochemistry after functionalization. Specifically, ordered mesoporous SBA-15 has been grafted with aminopropyl, etilenediamine, phosphatoethyl, propyl methacrylate, and carboxylic acid groups at different degrees of functionalization. To test the molecular adsorption and release features, three molecules of clinical interest have been selected, namely, antiresorptive zoledronic acid, amino acid L-tryptophan, and protein bovine serum albumin. Molecular loading and delivery aspects have been studied by emphasizing the host-guest interactions, which determine the adsorption and release behavior. It has been found that careful control of surface electrochemistry by functionalization determines the bioactive molecule adsorption whereas the release can be mainly thought of as a diffusion matter dependent on the surface area and molecule size. This enhanced approach opens up new ways to optimize molecule loading for specific clinical needs.

In vitro structural changes in porous HA/β-TCP scaffolds in simulated body fluid

Porous scaffolds of biphasic calcium phosphate (hydroxyapatite/beta-tricalcium phosphate (beta-TCP)) have been fabricated and changes induced both in phase composition and porous architecture by immersion in simulated body fluid (SBF) under static and orbital stirring conditions have been studied. The starting porous scaffolds exhibit a low and randomized micro- and mesoporosity, an interconnected macroporosity centered at 100 and 0.6microm, a fractal connectivity of D=2.981 and total percent porosity of ca. 80%. After immersion for up to 60days the micro- and mesoporosity increase slightly, which could be attributed to dissolution of the beta-TCP phase confirmed by transmission electron microscopy. The effects of the change in the porous framework with SBF immersion time favor the bioactive behavior of the tested materials, inducing a nucleation and growth of a nanocrystalline apatite phase as the interconnected macroporosity centered at 0.6microm is reduced. The macroporosity centered at 100microm is still stable after 60days in SBF. Therefore, these biphasic calcium phosphate porous scaffolds combine bioactive behavior with the stability of interconnected macroporosity over large periods of soaking time in SBF under static and orbital stirring conditions.

Silica Materials for Medical Applications

The two main applications of silica-based materials in medicine and biotechnology, i.e. for bone-repairing devices and for drug delivery systems, are presented and discussed. The influence of the structure and chemical composition in the final characteristics and properties of every silica-based material is also shown as a function of the both applications presented. The adequate combination of the synthesis techniques, template systems and additives leads to the development of materials that merge the bioactive behavior with the drug carrier ability. These systems could be excellent candidates as materials for the development of devices for tissue engineering.

Drug Confinement and Delivery in Ceramic Implants

Ordered silica-based mesoporous materials could be specially designed and chemically modified for the adsorption of drugs that would be locally released. The drug adsorption and release kinetics are controlled by several factors such as pore size, volume, architecture and chemistry of the silica walls.

Reported nanosafety practices in research laboratories worldwide.

An online survey shows that most researchers do not use suitable personal and laboratory protection equipment when handling nanomaterials that could become airborne.

Surface functionalization for tailoring the aggregation and magnetic behaviour of silica-coated iron oxide nanostructures

We report here a detailed structural and magnetic study of different silica nanocapsules containing uniform and highly crystalline maghemite nanoparticles. The magnetic phase consists of 5 nm triethylene glycol (TREG)- or dimercaptosuccinic acid (DMSA)-coated maghemite particles. TREG-coated nanoparticles were synthesized by thermal decomposition. In a second step, TREG ligands were exchanged by DMSA. After the ligand exchange, the ζ potential of the particles changed from -10 to -40 mV, whereas the hydrodynamic size remained constant at around 15 nm. Particles coated by TREG and DMSA were encapsulated in silica following a sol-gel procedure. The encapsulation of TREG-coated nanoparticles led to large magnetic aggregates, which were embedded in coalesced silica structures. However, DMSA-coated nanoparticles led to small magnetic clusters inserted in silica spheres of around 100 nm. The final nanostructures can be described as the result of several competing factors at play. Magnetic measurements indicate that in the TREG-coated nanoparticles the interparticle magnetic interaction scenario has not dramatically changed after the silica encapsulation, whereas in the DMSA-coated nanoparticles, the magnetic interactions were screened due to the function of the silica template. Moreover, the analysis of the AC susceptibility suggests that our systems essentially behave as cluster spin glass systems.

Insights into the microwave-assisted preparation of supported iron oxide nanoparticles on silica-type mesoporous materials

A detailed investigation on the microwave-assisted preparation of iron oxide nanoparticles on mesoporous Si-SBA-15 support is described, employing a dedicated single-mode microwave reactor with internal reaction temperature control. Using iron(II) chloride as iron precursor and ethanol as solvent, extensive optimization studies demonstrate that after 3–5 min at 150–200 °C well-defined 3–5 nm iron oxide nanoparticles (Fe2O3, hematite phase) are obtained. In contrast to the chosen reaction temperature, reaction time and stirring efficiency are of critical importance in the preparation of these supported nanoparticles. Extended reaction times (>10 min) lead to a significant proportion of larger aggregates while inefficient stirring also produces low quality nanoparticles as a result of poor dispersion and delivery of the iron precursor to the mesoporous support. Carefully executed control studies between microwave and conventionally heated experiments applying otherwise identical reaction conditions demonstrate that the quality of the obtained supported iron oxide nanoparticles is largely independent on the heating mode, as long as a the exact same temperature profile can be maintained.