Amino-modified mesoporous silica SBA-15 as bifunctional drug delivery system for cefazolin: Release profile and mineralization potential

doi:10.1016/j.matlet.2018.05.059

Materials Letters

Volume 227, 15 September 2018, Pages 136-140

https://doi.org/10.1016/j.matlet.2018.05.059 Get rights and content

Highlights

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The SBA-NH₂ exhibited higher adsorption efficiency of cefazolin compared to SBA-15.
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The prolonged cefazolin release profile from SBA-NH₂ was achieved.
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The SBA-NH₂ provided a complete cefazolin release in controlled manner.
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Progressive hydroxycarbonate apatite formation was observed for SBA-15 and SBA-NH₂.
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The SBA-NH₂ was characterized by delayed hydroxycarbonate apatite formation.

Abstract

In this paper the amino-modified mesoporous silica (SBA-NH₂) was investigated as a potential bifunctional drug delivery system for cefazolin with both prolonged drug release and mineralization properties. The primary SBA-15 was synthesized using sol-gel method and surface functionalization was carried out using post-synthesis grafting. The obtained SBA-NH₂ was characterized by higher adsorption efficiency of cefazolin with drug release prolonged to 7 days compared to primary SBA-15. The amino-modified SBA-15 exhibited also mineralization potential after immersion in simulated body fluid (SBF) with delayed hydroxycarbonate apatite (HCA) formation compared to SBA-15 which did not interrupt the cefazolin release in controlled manner. A bone-mineral-mimicking layer of HCA was formed on the SBA-NH₂ surface after 28 days in SBF.

Graphical abstract

Introduction

Ordered mesoporous silica materials SBA-15 understood as novel drug carriers which play an important role as biomaterial in orthopaedics are present in literature [1], due to their mineralization potential in simulated body fluid (SBF) leading to self formation of surface hydroxycarbonate apatite (HCA) with morphology and chemical composition similar to human bone apatite. Moreover SBA-15 are proven to be biocompatible and bioinert in tissue [2].

We are interested in the investigation of in vitro potential of amino-modified SBA-15 mesoporous silica (SBA-NH₂) as bifunctional drug delivery system for cefazolin which is a semi-synthetic cephalosporin for parenteral administration use in bacterial bone infections. The preferable electrostatic attraction between positively charged silica surface (R-NH₃⁺) and negatively charged cefazolin ions (Cef-COO⁻) might increase the drug loading capacity and prolong the release profile. After surgical implantation the proposed SBA-NH₂ bifunctional system should release the cefazolin in prolonged manner directly in the infected bone tissue and after complete drug release it should support the bone regeneration via delayed HCA formation. Such system will reduce the systemic side effects of administered drug and its later removal is not necessary because of its biocompatible composition with human bone apatite.

Section snippets

Synthesis and surface functionalization of SBA-15

The SBA-15 synthesis was performed according to the procedure proposed by Zhao et al. [3]. Material was obtained in sol-gel method using Pluronic P123 surfactant (Sigma-Aldrich, average M_n = 5800) as a structure directing agent and tetraethyl orthosilicate (TEOS, Sigma-Aldrich) as the precursor of silica. The synthesized and calcinated SBA-15 was filtered, rehydroxylated in HCl (18 wt%, POCH) for 24 h, then sieved through a 500 μm mesh to uniformize the silica grains (fraction 200–500 μm) and

Results and discussion

As presented in Fig. 1a the adsorption efficiency (%Ads) of the SBA-NH₂ was 6 times higher compared to SBA-15. The surface modification significantly increased the amount of drug adsorbed (from 1.3 ± 0.7 mg to 7.5 ± 0.9 mg per 100 mg for SBA-15 and SBA-NH₂, respectively) via chemisorption due to favourable electrostatic attraction between protonated silica surface (R-NH₃⁺) and Cef anions (Cef-COO⁻) in 0.05 M phosphate buffer. For SBA-15 the electrostatic repulsion between negatively charged

Conclusion

The surface amino-modified SBA-15 mesoporous silica led to the 6-times increase of the total amount of adsorbed Cef and caused the prolongation of Cef release to 7 days compared to unmodified SBA-15. Both SBA-15 and SBA-NH₂ exhibited the mineralization potential, with delayed HCA formation observed for SBA-NH₂ which provided the complete Cef release in controlled manner. Thus SBA-NH₂ material might be a potential bifunctional drug delivery system with both prolonged drug release and delayed

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