Drug loaded mesoporous silica nanoparticles for antimicrobial applications

摘要

Introduction: Mesoporous silica nanoparticles (MSNs) contain ordered arrangements of nanoscale pores (2-3 nm) templated by a surfactant in solution phase self-assembly. This porous, physically robust structure is ideal for the storage and release of drug. Traditionally, drug loading in MSN pores requires template removal and subsequent drug loading, resulting in low loading and short-term release, which are unsuitable for applications such as antimicrobial use. This study developed a synthesis for antimicrobial-templated MSNs. Objectives were to simplify synthesis and increase the degree of drug loading by templating pores with a self-assembling drug while maintaining an ordered mesoporous structure. It was hypothesized that this would result in inherently high drug loading and sustained release. Materials and Methods: MSNs were synthesized using a modified precipitation technique with tetraethyl orthosilicate as a silica source and a drug micellar network to template pores. Pore order was analyzed by X-ray diffraction (XRD). Pore size was calculated by N_2 adsorption. Drug loading was analyzed by thermogravimetric analysis. Field emission scanning and transmission electron microscopy (SEM and TEM) were used to Image particles. Drug release was monitored by UV-vis spectroscopy from suspended particles in PBS at 37°C. Results: Spherical 400 nm diameter particles were synthesized with an average drug content of 34% w/w. XRD revealed a semi-ordered pore structure with average d-spacing of 2.6 nm. Pore size was from 1.2 to 2 nm in diameter. Fig. 1 A shows a MSN fully loaded with drug post-synthesis, while B shows a particle post drug release. Cumulative drug release is shown in Fig. 2 as well as an incipient wetness-loaded MCM-41 MSN control. Discussion: Syntheses consistently produced spherical particles with high degrees of drug loading. Low, broad x-ray diffraction peaks are consistent with a disordered mesoporous structure, where pores are not necessarily aligned, but demonstrate an average periodicity (d-spacing). This d-spacing was approximately twice the pore width found by nitrogen adsorption, and agrees with SEM observations. SEM images demonstrate some drug loading obfuscating pore openings, but after drug removal these pores appear open and hollow, supporting the hypothesis that drug release was from pores and not just adsorbed material on the particle surface. Drug release was sustained over a longer period of time and at higher amounts than the traditional control (while still only releasing 34% of its total payload), showing promise for long term and high dosage antimicrobial applications. Conclusion: The novel synthesis developed in this study has produced MSNs with a high degree of internal pore drug loading exhibiting extended release. This was achieved while simplifying the synthesis procedure. These MSNs show great promise as carriers in composite applications such as drug eluting implants or antimicrobial surfaces for medical applications.