Insights into the intraparticle morphology of dendritic mesoporous silica nanoparticles from electron tomographic reconstructions.

HYPOTHESIS: Although many synthetic pathways allow to fine-tune the morphology of dendritic mesoporous silica nanoparticles (DMSNs), the control of their particle size and mesopore diameter remains a challenge. Our study focuses on either increasing the mean particle size or adjusting the pore size distribution, changing only one parameter (particle or pore size) at a time. The dependence of key morphological features (porosity; pore shape and pore dimensions) on radial distance from the particle center has been investigated in detail. EXPERIMENTS: Three-dimensional reconstructions of the particles obtained by scanning transmission electron microscopy (STEM) tomography were adapted as geometrical models for the quantification of intraparticle morphologies by radial porosity and chord length distribution analyses. Structural properties of the different synthesized DMSNs have been complementary characterized using TEM, SEM, nitrogen physisorption, and dynamic light scattering. FINDINGS: The successful independent tuning of particle and pore sizes of the DMSNs could be confirmed by conventional analysis methods. Unique morphological features, which influence the uptake and release of guest molecules in biomedical applications, were uncovered from analyzing the STEM tomography-based reconstructions. It includes the quantification of structural hierarchy, identification of intrawall openings and pores, as well as the distinction of pore shapes (conical vs. cylindrical).

Gastro-protective protein-silica nanoparticles formulation for oral drug delivery: In vitro release, cytotoxicity and mitochondrial activity.

Our contribution aims to provide an efficient solution to one of the major challenges of oral delivery of gastro-sensitive drugs, namely preventing their premature release and degradation in the gastric fluid in order to maximize the absorption in the small intestine. Our results show that a pH-responsive protein, i.e., succinylated ß-lactoglobulin (BL), together with the key attributes of mesoporous silica nanoparticles (MSNs), can synergetically reduce the release of the gastro-sensitive drug, omeprazole (OMP), in acidic pH and enhance the dissolution in intestinal pH conditions. Two families of MSNs were synthesized, MCM-48-based and dendritic-type MSNs, and both materials were additionally functionalized with trimethylsilyl groups to produce a hydrophobic surface that can further modulate the interaction of the MSNs with the succinylated protein in the nanoformulation. The methyl-functionalization of the MSNs also impacted on the physical state of the confined OMP and consequently on its release in near neutral pH. Our cytotoxicity screening revealed no particular mitochondrial dysfunction originating from the MSNs. Moreover, upon progressive release of the drug confined into dendritic-type MSNs, the cytotoxicity against tumorigenic and non-tumorigenic cells (Caco-2 and HCEC) was significantly lower in comparison to the drug pre-dissolved in DMSO.

A microfluidic approach to micromembrane synthesis for complex release profiles of nanocarriers.

Physically crosslinked microscale biomembranes synthesized from pure chitosan are designed and demonstrated for pH-triggered release of embedded functionalized mesoporous silica nanoparticles. Nanoparticle-loaded membranes are formed in a microfluidic channel at the junction between accurately controlled co-flowing streams to achieve highly tuneable membrane properties. After formation, the loaded membranes remain stable until contact with physiological acidic conditions, resulting in controlled nanoparticle release. Furthermore, nanoparticle-loaded membranes with complex layered architectures are synthesized using different flow schemes, thus enabling customized nanoparticle release profiles. These novel materials are well-suited for integration within small medical devices as well as off-chip applications.

Smart Protein-Based Formulation of Dendritic Mesoporous Silica Nanoparticles: Toward Oral Delivery of Insulin.

Oral insulin administration still represents a paramount quest that almost a century of continuous research attempts did not suffice to fulfill. Before pre-clinical development, oral insulin products have first to be optimized in terms of encapsulation efficiency, protection against proteolysis, and intestinal permeation ability. With the use of dendritic mesoporous silica nanoparticles (DMSNs) as an insulin host and together with a protein-based excipient, succinylated ß-lactoglobulin (BL), pH-responsive tablets permitted the shielding of insulin from early release/degradation in the stomach and mediated insulin permeation across the intestinal cellular membrane. Following an original in vitro cellular assay based on insulin starvation, direct cellular fluorescent visualization has evidenced how DMSNs could ensure the intestinal cellular transport of insulin.

In Vitro Dissolution, Cellular Membrane Permeability, and Anti-Inflammatory Response of Resveratrol-Encapsulated Mesoporous Silica Nanoparticles.

Sizing drugs down to the submicron and nanometer scale using nanoparticles has been extensively used in pharmaceutical industries to overcome the poor aqueous solubility of potential therapeutic agents. Here, we report the encapsulation and release of resveratrol, a promising anti-inflammatory and anticancer nutraceutical, from the mesopores of MCM-48-type silica nanospheres of various particle sizes, i.e., 90, 150, and 300 nm. Furthermore, the influence of the carrier pore size on drug solubility was also evaluated (3.5 vs 7 nm). From our results, it is observed that the saturated solubility could depend not only on the pore size but also on the particle size of the nanocarriers. Moreover, with our resveratrol-mesoporous silica nanoparticles formulation, we have observed that the permeability of resveratrol encapsulated in MCM-48 nanoparticles (90 nm) can be enhanced compared to a resveratrol suspension when tested through the human colon carcinoma cell monolayer (Caco-2). Using an in vitro NF-κB assay, we showed that resveratrol encapsulation did not alter its bioactivity and, at lower concentration, i.e., 5 µg mL-1, resveratrol encapsulation provided higher anti-inflammatory activity compared to both resveratrol suspension and solution. All combined, the reported results clearly highlight the potential of small size mesoporous silica nanoparticles as next generation nanocarriers for hydrophobic drugs and nutraceuticals.

Functionalization of mesoporous materials for lanthanide and actinide extraction.

Among the energy sources currently available that could address our insatiable appetite for energy and minimize our CO2 emission, solar, wind, and nuclear energy currently occupy an increasing portion of our energy portfolio. The energy associated with these sources can however only be harnessed after mineral resources containing valuable constituents such as actinides (Ac) and rare earth elements (REEs) are extracted, purified and transformed into components necessary for the conversion of energy into electricity. Unfortunately, the environmental impacts resulting from their manufacture including the generation of undesirable and, sometimes, radioactive wastes and the non-renewable nature of the mineral resources, to name a few, have emerged as challenges that should be addressed by the scientific community. In this perspective, the recent development of functionalized solid materials dedicated to selective elemental separation/pre-concentration could provide answers to several of the above-mentioned challenges. This review focuses on recent advances in the field of mesoporous solid-phase (SP) sorbents designed for REEs and Ac liquid-solid extraction. Particular attention will be devoted to silica and carbon sorbents functionalized with commonly known ligands, such as phosphorus or amide-containing functionalities. The extraction performances of these new systems are discussed in terms of sorption capacity and selectivity. In order to support potential industrial applications of the silica and carbon-based sorbents, their main drawbacks and advantages are highlighted and discussed.