1.D.73 The Mesoporous Silica Nanopore (SilNP) Family
An MCM-41-type mesoporous silica nanoparticle (MSN) material with a large average pore diameter (5.4 nm) has been synthesized and characterized (Slowing et al. 2007). The in vitro uptake and release profiles of cytochrome c by the MSN were investigated. The enzymatic activity of the released protein was quantitatively analyzed and compared with that of the native cytochrome c in physiological buffer solutions. It was found that the enzymes released from the MSNs are still functional and highly active in catalyzing the oxidation of 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonate) (ABTS) by hydrogen peroxide. In contrast to the fact that cytochrome c is a cell-membrane-impermeable protein, the cytochrome c-encapsulated MSNs could be internalized by live human cervical cancer cells (HeLa), and the protein could be released into the cytoplasm. Slowing et al. 2007 envision that these MSNs with large pores could serve as a transmembrane delivery vehicle for controlled release of membrane-impermeable proteins in live cells, which could lead to biotechnological applications including therapeutics and metabolic manipulation of cells. Furthermore, BBB-impermeable mesoporous silica nanoparticle codelivery system markedly enhanced the transport efficiency to the brain in vivo by BN1-functionalized. These findings indicate that designed aqueous molecules not only are capable of traversing the BBB but also serve as a viable strategy for central-nervous-system-targeted drug delivery (Zhang et al. 2024).
Scanning electrochemical microscopy (SECM) has been used to study the dynamics of molecular transport across the ultrathin silica nanoporous membrane consisting of sub-3 nm-in-diameter perpendicular channels. Yao et al. 2018 focused on the quantitative assessment of permselectivity and permeability of this membrane, and the effect of radial electrical double layer (EDL) on them. By SECM imaging, it was phenomenologically observed that the membrane, with a negatively charged surface, exhibited permselectivity to anionic molecules, for instance hexacyanoruthenate(II) (Ru(CN)6(4-)). Permselective transport of Ru(CN)6(4-) was more favored at a high concentrations of KCl. The high permeability (up to 35 mum/sec) was ascribed to the straight channel structure and ultrahigh channel density of 4 x 1012/cm2. Moreover, the permeability was varied from 35 mum/sec to 2.5 mum/sec when decreasing the concentration of KCl from 1.0 M to 0.01 M, corroborating the electrostatic origin of membrane permselectivity. On the other hand, the simulated concentration profiles at both sides of the membrane suggested that molecular transport across the membrane was mainly driven by the large transmembrane concentration gradient. These results help to quantitatively understand the molecular transport selectivity and dynamics across nanoporous membranes, and to allow rational design of artificial molecular sieving membranes (Yao et al. 2018).
A drug release model based on mesocellular foam silica (MCF) for Biopharmaceutics Classification System (BCS) II drugs has been described (Liu et al. 2019). A three-level two-factorial design was carried out for the exploration of the influence of the pore size of MCF (X1) and drug-loading degree (X2) for drug release behavior. Cumulative release in 1 h (Y1), cumulative release in 24 h (Y2), and rate constant k (Y3) were selected as dependent response variables. A series of MCFs (7MCF, 12MCF, and 17MCF) with arithmetic increased pore diameters was synthesized as drug carriers. The morphologies and structures of MCFs and pore size distributions were detected by scanning EM, transmission EM, and nitrogen adsorption analysis. With celecoxib as a model drug, nine drug-loaded samples were prepared and further characterized by differential scanning calorimetry and X-ray diffraction analyses (Liu et al. 2019).