Use of Materials Based on Polymeric Silica as Bone-Targeted Drug Delivery Systems for Metronidazole.

Katarzyna Czarnobaj,Magdalena Prokopowicz,Katarzyna Greber

doi:10.3390/ijms20061311

Katarzyna Czarnobaj, Magdalena Prokopowicz + Show 1 more

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https://doi.org/10.3390/ijms20061311

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Abstract

Mesostructured ordered silica-based materials are the promising candidates for local drug delivery systems in bone disease due to their uniform pore size and distribution, and high surface area which affect their excellent adsorption properties, good biocompatibility and bioactivity, and versatile functionalization so that their properties can be controlled. Ordered mesoporous silica (MCM-41 type) was synthesized by a surfactant-assisted sol-gel process using tetraethoxysilane as a silica precursor and hexadecyltrimethylammonium bromide as the structure-directing agent. Functionalized silica materials containing various types of organic groups (3-aminopropyl, 3-mercaptopropyl, or 3-glycidyloxypropyl groups) were synthesized by the post-grafting method onto pre-made mesoporous silica. Comparative studies of their structural characteristics, the surface mineralization activity and release properties for the model drug Metronidazole (MT) were then conducted. It has been found that porosity parameters, mineralization activity and adsorption/release of metronidazole from mesoporous channels of silica can be regulated using functional groups which are chemically bounded with an outer silica surface. The preferential mineral nucleation was found on negatively charged surfaces—MCM-41, and mercaptopropyl and glycidyloxypropyl functionalized silica (MCM-SH and MCM-epoxy, respectively) in simulated body fluid (SBF solution), as well as a sustained release of MT. In contrast to them, aminopropyl-functionalized samples (MCM-NH2) achieved a high MT release rate. These results confirm the potential of silica-based materials for local therapeutic applications (as drug carriers and bone substitutes) in bone disease.

Highlights

The most common ways of delivering drugs to the body are oral and parenteral administration
The ability of biomaterials to integrate with bone tissue can be evaluated using the simulated body fluid (SBF) test to study the in vitro formation of bone-like apatite at the surface of such materials when immersed in SBF [29]
The mineralization activity of oxide materials decides both the chemical composition and the surface properties, especially the porosity and hydrophilicity of the surface [30]. These aspects suggest that ordered mesoporous silica materials, such as MCM-41 or functionalized MCM-41, thanks to high surface area, appropriate size of pores and the occurrence of reactive groups (-OH, -NH2, -SH, -epoxy), are the promising candidates as bioactive bone tissue substitutes

Summary

Introduction

The most common ways of delivering drugs to the body are oral and parenteral administration. These manners have lower efficiency for some therapies, e.g., treatment of bone diseases/infections. The desired carrier in the local treatment of bones diseases should demonstrate the possibility to simultaneously introduce in situ drug release in combination with the filling and regeneration of the tissue defect, for example to stimulate the growth of the natural tissue helping in its replacement or complementation [1,2,3]. The ordered mesoporous silica-based materials are the leading candidates in tissue reconstruction technology. Their characteristic features include a low susceptibility to bacterial colonization, and absolute resistance to corrosion, unlike metallic implants. Because of their high surface area, controllable pore size, narrow pore size distribution, thermal and mechanical stability and easy surface functionalization, they may be used as carrier designated for the controlled release of therapeutic drugs [4,5,6,7,8,9,10]

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