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