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DEBASISH MONDAL, Andri K Riau, Elavazhagan Murugan, Thet Tun Aung, Bo Liedberg, Subbu S Venkatraman, Jodhbir S Mehta; Vancomycin incorporated collagen hydrogel implant for the prevention of ocular infections . Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4135.
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© ARVO (1962-2015); The Authors (2016-present)
To develop a sustained delivery system to improve the release kinetics of vancomycin as well as its therapeutic effectiveness to prevent postoperative corneal infection.
Vancomycin was incorporated into an engineered collagen hydrogel (10 and 15 wt%) scaffold through N-ethyl-N'-[3-dimethylaminopropyl] carbodiimide/N-hydroxy succinimide (EDC/NHS) crosslinking technique. Vancomycin incorporation into the collagen hydrogel was examined by fourier transform infrared spectroscopy (FTIR) and quantified spectrophotometrically after collagen digestion with collagenase. Mechanical stability of hydrogel was measured by Instron instrument. In vitro release profile of vancomycin was measured in PBS at 37°C. Structural integrity of released vancomycin was assessed by circular dichroism (CD) spectroscopy. The minimum inhibitory concentration (MIC) of control and released vancomycin against S.aureus (SA) was determined by inoculating with bacterial suspension (106 colony-forming unit/ml). The wells were examined spectrophotometrically for visible bacterial growth as evidenced by turbidity after 24h incubation at 37°C.
FTIR spectrum showed the incorporation of vancomycin in the collagen hydrogel as evidenced by presence of characteristic peaks of vancomycin (3075 cm-1, 1640 cm-1, and 1545 cm-1and 1423 cm-1, the bands were attributed to phenolic O-H, C=O stretching, C=C and C-C mode of vibration, respectively). Mechanical test result showed 15% collagen hydrogel yielded significantly higher tensile strength compared to the 10% hydrogel (0.317 ± 0.021 and 0.259 ± 0.007 MPa for 15% and 10% respectively, p=0.03). The addition of vancomycin in the hydrogel slightly reduced the tensile strength and Young’s modulus, but the difference was not significant (p=0.3). Vancomycin release pattern and amount was same for the different percentage (10% and 15%) hydrogel (p>0.05). The release was in a sustained manner for 7 days period with concentrations above the theoretical MIC of vancomycin against SA (2 µg/ml). Antimicrobial assay showed that the MIC of released vancomycin up to day 5 was the same as control (1 µg/ml), but MIC on day 7 was increased to 4 µg/ml. CD result revealed significant perturbation of vancomycin structure on day 7.
Our study suggests that collagen hydrogel implant can be used as a delivery system of vancomycin for 7 days above MIC, to prevent the postoperative ocular infection.
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