Silica-based mesoporous nanoparticles for controlled drug delivery

Abstract

Drug molecules with lack of specificity and solubility lead patients to take high doses of the drug to achieve sufficient therapeutic effects. This is a leading cause of adverse drug reactions, particularly for drugs with narrow therapeutic window or cytotoxic chemotherapeutics. To address these problems, there are various functional biocompatible drug carriers available in the market, which can deliver therapeutic agents to the target site in a controlled manner. Among the carriers developed thus far, mesoporous materials emerged as a promising candidate that can deliver a variety of drug molecules in a controllable and sustainable manner. In particular, mesoporous silica nanoparticles are widely used as a delivery reagent because silica possesses favourable chemical properties, thermal stability and biocompatibility. Currently, sol-gel-derived mesoporous silica nanoparticles in soft conditions are of main interest due to simplicity in production and modification and the capacity to maintain function of bioactive agents. The unique mesoporous structure of silica facilitates effective loading of drugs and their subsequent controlled release. The properties of mesopores, including pore size and porosity as well as the surface properties, can be altered depending on additives used to fabricate mesoporous silica nanoparticles. Active surface enables functionalisation to modify surface properties and link therapeutic molecules. The tuneable mesopore structure and modifiable surface of mesoporous silica nanoparticle allow incorporation of various classes of drug molecules and controlled delivery to the target sites. This review aims to present the state of knowledge of currently available drug delivery system and identify properties of an ideal drug carrier for specific application, focusing on mesoporous silica nanoparticles.

Keywords: Mesoporous silica nanoparticle; chemotherapy; controlled release; sol-gel process; targeted drug delivery.

Figure 1.

Diagrammatic presentation showing (a) the chemotherapeutic agent release from ‘smart’ pH-responsive TiO2 nanoparticles (adopted from Zhang et al.) and (b) (i) the fabrication process of TiO₂ nanotube and (ii) different methods of drug loading into TiO₂ nanotubes using HRP, involving immersion without surface modification of nanotubes (physisorption), immersion after OPDA modification of the upper nanotube layer (physisorption with hydrophobic cap), covalently linked HRP over the entire tubes (covalently linked nanotubes) and OPDA cap modified upper nanotube layer and HRP covalently linked lower nanotube layer (covalently linked with cap) (adopted from Song et al.). HRP: horseradish peroxidise; OPDA: octadecylphosphonic acid.

Figure 2.

Illustration of the sol-gel process in the synthesis of MSN. MSN: mesoporous silica nanoparticle; TEOS: tetraethyl orthosilicate.

Figure 3.

MSNs showing capping structure useful for controlled release. CdS: cadmium sulphide.

Figure 4.

Schematic presentation of PAA-MSN preparation process achieved from Li et al. PAA: poly(acrylic acid); MSN: mesoporous silica nanoparticle; CTAB: N-cetyltrimethylammonium bromide; TMB: trimethylbenzene.

Figure 5.

The graph showing greater DOX release from DOX in MSN-PAA in (a) 2 mM of glutathione medium compared to (b) without glutathione medium. PAA: poly(acrylic acid); MSN: mesoporous silica nanoparticle.