Functionalized Mesoporous Silica Nanoparticles as Delivery Systems for Doxorubicin: Drug Loading and Release

Candace M Day,Sanjay Garg,Sally E Plush,Martin J Sweetman,Yunmei Song

doi:10.3390/app11136121

Candace M Day, Sanjay Garg + Show 3 more

Open Access

https://doi.org/10.3390/app11136121

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Journal: Applied Sciences	Publication Date: Jun 30, 2021
Citations: 7	License type: CC BY 4.0

Affiliation: University of South Australia

Abstract

Functionalized nanoparticles have played a major role in the field of targeted therapy, owing to their ability to control the release and for the selective delivery of entrapped materials to tumours. In this work, we described the loading capacity and in vitro release kinetics of mesoporous silica nanoparticles (MSNs), functionalized with Poly-L-Histidine and Tamoxifen. The model drug Doxorubicin (DOX) was successfully encapsulated into MSN-based systems, using the technique of solvent immersion. A post-surface grafting loading method was investigated on functionalized systems, with DOX loading content determined using HPLC. Dialysis bag diffusion was employed to investigate the release kinetics of DOX-loaded-systems at pH 7.4 and 5. The amount of DOX released from native MSNs systems over a 72 h period at pH 5 was approximately 40%; and at pH 7.4 ≈ 30%. A moderate pH dependent release behaviour was observed with both our functionalized systems: DOX@MSN-PLH and DOX@MSN-PLH-TAM; with approximately 5% of DOX released from DOX@MSN-PLH-TAM at pH 7.4 and about 9% released at pH 7.4 over 72 h. The maximal cumulated release of DOX molecules from DOX@MSN-PLH after 72 h was ≈18% at pH 7.4 and ≈23% at pH 5, respectively. The outcome of this work offers a promising contribution towards building future stimuli-responsive nano-drug delivery systems.

Highlights

IntroductionPublisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations
By developing advanced drug delivery systems (DDSs), therapeutic compounds of interest can be entrapped within nanoparticle matrices or conjugated to different nanosystems [2,3], drug molecules can be delivered to designated molecular targets at much lower doses, and over longer time periods [2,3,4]
DOX was successfully encapsulated into three mesoporous silica nanoparticles (MSNs)-based systems, namely MSN, MSN-PLH and MSN-PLH-TAM, using a post grafting loading method

Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Means loaded) are grafted with solution of DOX, the DOX molecules diffuse into the porous channels of the MSNs. The resulting DOX@MSNs (in which @ means loaded) are grafted with PLH and TAM, method, functionalized MSN-PLH-TAM willthe be post-surface immersed into a stirred solution of forming fully (Figure 2a). The resulting DOX@MSN-PLH-TAM particles are collected centrifugation In our this novel systems interested (Figure 1),inusing the unconventional post-surface grafting study,MSN-based we are the loading of DOX into our novel MSN-based loading The This unconventional post-surface grafting of loading approach which each surface functionalization withwhich the pre-surface This isduring expected to step avoidofthe leakage of DOX molecules may occur grafting method. Hance the release of entrapped DOX molecules in acidic tumour microenvironments

General Methods and Materials

Loading of DOX onto MSN-Based Systems

In-Vitro Release Kinetics

Drug Loading

Conclusions