Electrosprayed mesoporous particles for improved aqueous solubility of a poorly water soluble anticancer agent: in vitro and ex vivo evaluation

open access articleEncapsulation of poorly water-soluble drugs into mesoporous materials (e.g. silica) has evolved as a favorable strategy to improve drug solubility and bioavailability. Several techniques (e.g. spray drying, solvent evaporation, microwave irradiation) have been utilized for the encapsulation of active pharmaceutical ingredients (APIs) into inorganic porous matrices. In the present work, a novel chalcone (KAZ3) with anticancer properties was successfully synthesized by Claisen-Schmidt condensation. KAZ3 was loaded into mesoporous (SBA-15 and MCM-41) and non-porous (fumed silica, FS) materials via two techniques; electrohydrodynamic atomization (EHDA) and solvent impregnation. The effect of both loading methods on the physicochemical properties of the particles (e.g. size, charge, entrapment efficiency, crystallinity, dissolution and permeability) was investigated. Results indicated that EHDA technique can load the active in a complete amorphous form within the pores of the silica particles. In contrast, reduced crystallinity (~79%) was obtained for the solvent impregnated formulations. EHDA engineered formulations significantly improved drug dissolution up to 30-fold, compared to the crystalline drug. Ex vivo studies showed EHDA formulations to exhibit higher permeability across rat intestine than their solvent impregnated counterparts. Cytocompatibility studies on Caco-2 cells demonstrated moderate toxicity at high concentrations of the anticancer agent. The findings of the present study clearly show the immense potential of EHDA as a loading technique for mesoporous materials to produce poorly water-soluble API carriers of high payload at ambient conditions. Furthermore, the scale up potential in EHDA technologies indicate a viable route to enhance drug encapsulation and dissolution rate of loaded porous inorganic materials

A novel approach to modelling water transport and drug diffusion through the stratum corneum

<p>Abstract</p> <p>Background</p> <p>The potential of using skin as an alternative path for systemically administering active drugs has attracted considerable interest, since the creation of novel drugs capable of diffusing through the skin would provide a great step towards easily applicable -and more humane- therapeutic solutions. However, for drugs to be able to diffuse, they necessarily have to cross a permeability barrier: the <it>stratum corneum </it>(SC), the uppermost set of skin layers. The precise mechanism by which drugs penetrate the skin is generally thought to be diffusion of molecules through this set of layers following a "tortuous pathway" around corneocytes, i.e. impermeable dead cells.</p> <p>Results</p> <p>In this work, we simulate water transport and drug diffusion using a three-dimensional porous media model. Our numerical simulations show that diffusion takes place through the SC regardless of the direction and magnitude of the fluid pressure gradient, while the magnitude of the concentrations calculated are consistent with experimental studies.</p> <p>Conclusions</p> <p>Our results support the possibility for designing arbitrary drugs capable of diffusing through the skin, the time-delivery of which is solely restricted by their diffusion and solubility properties.</p

Carbon Adsorbents With Dual Porosity for Efficient Removal of Uremic Toxins and Cytokines from Human Plasma

Abstract The number of patients with chronic kidney disease increases while the number of available donor organs stays at approximately the same level. Unavoidable accumulation of the uremic toxins and cytokines for these patients comes as the result of malfunctioning kidneys and their high levels in the blood result in high morbidity and mortality. Unfortunately, the existing methods, like hemodialysis and hemofiltration, provide only partial removal of uremic toxins and/or cytokines from patients’ blood. Consequently, there is an increasing need for the development of the extracorporeal treatments which will enable removal of broad spectrum of uremic toxins that are usually removed by healthy kidneys. Therefore, in this work we developed and tested ordered mesoporous carbons as new sorbents with dual porosity (micro/meso) that provide selective and efficient removal of a broad range of uremic toxins from human plasma. The new sorbents, CMK-3 are developed by nanocasting methods and have two distinct pore domains, i.e. micropores and mesopores, therefore show high adsorption capacity towards small water soluble toxins (creatinine), protein-bound molecules (indoxyl sulfate and hippuric acid), middle molecules (β-2-microglobulin) and cytokines of different size (IL-6 and IL-8). Our results show that small amounts of CMK-3 could provide selective and complete blood purification

Silver decorated mesoporous carbons for the treatment of acute and chronic wounds, in a tissue regeneration context

Introduction: Silver decorated mesoporous carbons are interesting systems that may offer effective solutions for advanced wound care products by combining the well-known antimicrobial activity of silver nanoparticles with the versatile properties of ordered mesoporous carbons. Silver is being used as a topical antimicrobial agent, especially in wound repair. However, while silver shows bactericidal properties, it is also cytotoxic at high concentrations. Therefore, the incorporation of silver into ordered mesoporous carbons allows to exploit both silver’s biological effects and mesoporous carbons’ biocompatibility and versatility with the purpose of conceiving silver-doped materials in light of the growing health concern in wound care. Methods: The wound healing potential of an ordered mesoporous carbon also doped with two different loadings of silver nanoparticles (2 wt% and 10 wt%), was investigated through a biological assessment study based on different assays (cell viability, inflammation, antibacterial tests, macrophage-conditioned fibroblast and human keratinocyte cell cultures). Results: The results show silver-doped ordered mesoporous carbons to positively condition cell viability, with a cell viability percentage >70% even for 10 wt% Ag, to modulate the expression of inflammatory cytokines and of genes involved in tissue repair (KRT6a, VEGFA, IVN) and remodeling (MMP9, TIMP3) in different cell systems. Furthermore, along with the biocompatibility and the bioactivity, the silver-doped ordered mesoporous carbons still retain an antibacterial effect, as shown by a maximum of 13.1% of inhibited area in the Halo test. The obtained results clearly showed that the silver-doped ordered mesoporous carbons exhibit both good biocompatibility and antibacterial effect with enhanced re-epithelialization, angiogenesis promotion and tissue regeneration. Discussion: These findings suggest that the exceptional properties of silver-doped ordered mesoporous carbons could be exploited in the treatment of acute and chronic wounds and that such carbon materials could be potential candidates for use in medical devices for wound healing purposes, in particular, the 10 wt% loading, as the results showed to be the most effective