Abstract
In this study we have investigated the suitability of a number of different mesoporous silica nanoparticle structures for carrying a drug cargo. We have fully characterized the nanoparticles in terms of their physical parameters; size, surface area, internal pore size and structure. These data are all required if we are to make an informed judgement on the suitability of the structure for drug delivery in vivo. With these parameters in mind, we investigated the loading/unloading profile of a model therapeutic into the pore structure of the nanoparticles. We demonstrate that the release can be controlled by capping the pores on the nanoparticles to achieve temporal control of the unloading. We have also examined the rate and mechanism of the degradation of the nanoparticles over an extended period of time. The eventual dissolution of the nanoparticles after cargo release is a desirable property for a drug delivery system.
Highlights
Mesoporous silica nanoparticles (MSNPs) are receiving increasing interest from the scientific community for their potential as drug delivery systems both in vitro and in vivo
The silica surface has a high density of silanol groups which can be modified with a wide range of organic functional groups [3], allowing for modification with targeting agents such as peptides, antibodies or folic acid, or biocompatible polymers such as polyethylene glycol (PEG) to minimize opsonization which would lead to the rapid clearance of the nanoparticles [4]
The MSNPs were capped with a repeating sandwich layer of the polycation, poly-allylamine hydrochloride (PAH; Sigma-Aldrich) and the polyanion, poly-sodium 4-styrene sulfonate (PSS; Sigma). 200 mg MSNP was added to 20 mL Capping Buffer (20 mM Tris, 20 mM NaCl, pH 8.5) and resuspended by sonication for three minutes
Summary
Mesoporous silica nanoparticles (MSNPs) are receiving increasing interest from the scientific community for their potential as drug delivery systems both in vitro and in vivo (see [1], references 1–17). MSNPs typically have particle diameters in the 50-300 nm range and narrow pore size distributions of the order 2-6 nm. Their structure and morphology are controllable at both the nanometre and micrometre scale, yielding high surface area and pore volumes of the MSNPs and enabling a high cargo carrying capacity. The microvasculature surrounding tumours is highly permeable and leaky, and tumours have less efficient efflux mechanisms (the EPR effect) which will influence the overall bio-distribution. This means that nanoparticles of the right size will likely passively accumulate at the tumour site. We have evaluated the nanoparticles in terms of their physical and nanostructural attributes, interaction with model-drug molecules, and timedependent behaviour in conditions that mimic those of the human body
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