Degradable Drug Carriers: Vanishing Mesoporous Silica Nanoparticles

Moeller, Karin und Bein, Thomas (2019): Degradable Drug Carriers: Vanishing Mesoporous Silica Nanoparticles. In: Chemistry of Materials, Bd. 31, Nr. 12: S. 4364-4378

Abstract

The versatile potential of mesoporous silica nanoparticles (MSNs) as drug delivery agents for cytotoxic or chemically sensitive (macro)molecules has been demonstrated in numerous in vitro and in vivo studies. Nevertheless, translation of MSNs into clinical applications still appears to be difficult for several reasons-one prominent concern being the uncertainty about the fate of these nanoparticles in the body. The degradability of drug carriers is a prerequisite for avoiding potentially hazardous effects upon application in living systems. Furthermore, a timely degradation might even enhance medical efficacy through efficient drug release. Knowledge about the stability of drug carrier systems and about the parameters that might influence their degradation process is therefore very valuable for developing optimal carrier designs. Hence, the hydrolytic stability/degradation of MSNs is expected to be a key feature regarding potential medical applications of mesoporous silica. So far, conclusive studies addressing the hydrolytic or biodegradability of MSNs are limited and the available data sometimes appear to be contradictory. Here, we performed a comprehensive evaluation comparing the degradability of a number of different MSNs under biomedically relevant conditions by using low particle concentrations. We synthesized MSNs at acidic, neutral, or basic pH. MSNs at basic pH were prepared as pure silica MSNs and as hybrid MSNs containing functional amino and mercapto groups as well as containing additional redox-sensitive disulfide entities, all integrated via co-condensation. These samples were synthesized following a common recipe, even when changing the particle size, in order to minimize the influence of particle preparation on the dissolution kinetics. The degradation process was monitored in different buffers over short and long exposure times using pristine particles or MSNs decorated with a variety of frequently used surface attachments. The quantitative assessment of the degradation process by inductively coupled plasma-optical emission spectrometry was complemented with transmission electron microscopy as well as UV-vis and FTIR spectroscopy. Cross-polarized and directly polarized Si-29 solid-state NMR was applied to identify differences in connectivity in the silica network. We find that the dissolution rate at low concentrations is predominantly governed by (i) the silica network connectivity, determined by the synthesis pH and co-condensation, and (ii) the silica building blocks. Thus, co-condensed MSNs with "interrupted" networks made under basic conditions degrade fastest and nearly completely within a few hours independent of particle size, while additional disulfide linkers in the pore walls retard this process. This is strongly contrasted by the behavior of purely siliceous MSNs, which are very stable when made under acidic conditions but show increasing degradability when made at higher pH. Hence, in this study, we demonstrate that the aqueous stability of mesoporous silica nanoparticles can be widely tuned from almost complete to nearly no degradability under medically relevant conditions. These results establish a new set of design rules for the adaptation of multifunctional MSNs to the requirements of desired scenarios in targeted drug delivery.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Chemie und Pharmazie > Department Chemie ; Physik
• Themengebiete: 500 Naturwissenschaften und Mathematik > 540 Chemie ; 500 Naturwissenschaften und Mathematik > 530 Physik
• ISSN: 0897-4756
• Sprache: Englisch