Vancomycin-Loaded Gel Ocular Drug Delivery System for Treatment of Endophthalmitis

Year 2024, Volume: 28 Issue: 3, 579 - 588, 30.06.2024

Ebru Erdal

https://doi.org/10.16984/saufenbilder.1354947

Abstract

In case of endophthalmitis, which develops as a result of microbial infection of the intraocular tissues, is not treated, it can lead to anatomical or functional losses in the eye. Intravitreal injections are the most preferred method in the treatment of endophthalmitis, which can be exogenous or endogenous. The combination of antibiotics effective against bacteria has disadvantages such as re-injection, unresponsiveness to treatment, and drug toxicity. Treatment in which antibiotics effective against both gram (+) and gram (-) bacteria are used in combination has disadvantages such as re-injection, unresponsiveness to treatment, and drug toxicity. In order to overcome these disadvantages, studies are carried out to develop injectable forms of active substances that provide long-term release. In this study, the antibiotic Vancomycin (Van), which is frequently used in the treatment of endophthalmitis, was loaded into alginate hydrogels; characterization, in vitro release and toxicity were determined. Its morphology was visualized by environmental scanning electron microscopy (ESEM) and Fourier transform infrared (FTIR) spectroscopy was used to characterize changes in chemical structure. The release of Van from the hydrogels continued for more than 2 weeks. It was determined that the toxicity of free Van decreased with loading of hydrogels. Its antibacterial activity was evaluated with the disc diffusion test and it was determined that it was more effective against Staphylococcus aureus.

Keywords

Endophthalmitis, Vancomycin, Hydrogel, Alginate, Antibacterial

Supporting Institution

Ankara Yıldırım Beyazıt Üniversitesi, BAP

Project Number

THD-2023-2475

Thanks

This study was financially supported by Ankara Yıldırım Beyazıt University with the project number THD-2023-2475.

References

• [1] M. L. Durand, "Endophthalmitis," Clinical Microbiology and Infection, vol. 19, no. 3, pp. 227-234, 2013.
• [2] S.-J. Sheu, "Endophthalmitis," Korean Journal of Ophthalmology, vol. 31, no. 4, pp. 283-289, 2017.
• [3] M. Kernt, A. Kampik, "Endophthalmitis: Pathogenesis, clinical presentation, management, and perspectives," (in English), Clinical Ophthalmology, vol. 4, pp. 121-135, 2010.
• [4] C. Fabiani, M. Agarwal, M. Dogra, G. M. Tosi, J. L. Davis, "Exogenous Endophthalmitis," Ocular immunology and inflammation, pp. 1-10, 2022.
• [5] K. Vaziri, S. G. Schwartz, K. Kishor, H. W. Flynn, "Endophthalmitis: state of the art," (in English), Clinical Ophthalmology, vol. 9, pp. 95-108, 2015.
• [6] T. Imamura, M. Kakinoki, D. Hira, T. Kitagawa, S. Ueshima, M. Kakumoto, T. Terada, I. Kawamoto, M. Murase, M. Ohji, "Pharmacokinetics of Intravitreal Vancomycin and Ceftazidime in Silicone Oil-Filled Macaque Eyes," (in English), Translational Vision Science and Technology, vol. 10, no. 3, Mar 2021.
• [7] D. B. Roth, H. W. Flynn, "Antibiotic selection in the treatment of endophthalmitis: The significance of drug combinations and synergy," (in English), Survey of Ophthalmology, vol. 41, no. 5, pp. 395-401, Mar-Apr 1997.
• [8] A. Fahr, X. Liu, "Drug delivery strategies for poorly water-soluble drugs," (in English), Expert Opinion on Drug Delivery, vol. 4, no. 4, pp. 403-416, Jul 2007.
• [9] P. van Hoogevest, X. L. Liu, A. Fahr, "Drug delivery strategies for poorly water-soluble drugs: the industrial perspective," (in English), Expert Opinion on Drug Delivery, vol. 8, no. 11, pp. 1481-1500, Nov 2011.
• [10] C. L. Schepens, A. Neetens, The vitreous and vitreoretinal interface. Springer Science & Business Media, 2012.
• [11] J. Kopeček, "Hydrogel biomaterials: a smart future?" Biomaterials, vol. 28, no. 34, pp. 5185-5192, 2007.
• [12] E. M. Ahmed, "Hydrogel: Preparation, characterization, and applications: A review," (in English), Journal of Advanced Research, vol. 6, no. 2, pp. 105-121, Mar 2015.
• [13] K. Deligkaris, T. S. Tadele, W. Olthuis, A. van den Berg, "Hydrogel-based devices for biomedical applications," (in English), Sensor Actuat B-Chemical, vol. 147, no. 2, pp. 765-774, Jun 3 2010.
• [14] A. Gürsoy, "Kontrollü salım sistemleri," Kontrollü Salım Sistemleri Derneği, İstanbul, pp. 3-6, 2002.
• [15] D. A. Gyles, L. D. Castro, J. O. C. Silva, R. M. Ribeiro-Costa, "A review of the designs and prominent biomedical advances of natural and synthetic hydrogel formulations," (in English), European Polymer Journal, vol. 88, pp. 373-392, Mar 2017.
• [16] S. Garg, A. Garg, R. Vishwavidyalaya, "Hydrogel: Classification, properties, preparation and technical features," Asian Journal of Biomaterial Research, vol. 2, no. 6, pp. 163-170, 2016.
• [17] M. Zhang, X. Zhao, "Alginate hydrogel dressings for advanced wound management," (in English), International Journal of Biological Macromolecules, vol. 162, pp. 1414-1428, Nov 1 2020.
• [18] A. D. Augst, H. J. Kong, D. J. Mooney, "Alginate hydrogels as biomaterials," Macromolecular bioscience, vol. 6, no. 8, pp. 623-633, 2006.
• [19] Y. A. Khan, K. Ozaltin, A. Bernal-Ballen, A. Di Martino, "Chitosan-alginate hydrogels for simultaneous and sustained releases of ciprofloxacin, amoxicillin and vancomycin for combination therapy," (in English), Journal of Drug Delivery Science and Technology, vol. 61, Feb 2021.
• [20] R. Supino, "MTT assays," In vitro toxicity testing protocols, pp. 137-149, 1995.
• [21] C. J. Maxwell, A. M. Soltisz, W. W. Rich, A. Choi, M. A. Reilly, K. E. Swindle-Reilly, "Tunable alginate hydrogels as injectable drug delivery vehicles for optic neuropathy," (in English), Journal of Biomedical Materials Research Part A, vol. 110, no. 10, pp. 1621-1635, Oct 2022.
• [22] B. Sadeghi, M. Jamali, S. Kia, N. A. AMINI, S. Ghafari, "Synthesis and characterization of silver nanoparticles for antibacterial activity," International Journal of Nano Dimension, Vol. 1 no. 2, pp. 119-124, 2010.
• [23] L. Y. Xue, T. Deng, R. Guo, L. Peng, J. Guo, F. Tang, J. Lin, S. Jiang, H. Lu, X. Liu, L. A. Deng, "A Composite Hydrogel Containing Mesoporous Silica Nanoparticles Loaded with Artemisia argyi Extract for Improving Chronic Wound Healing" (in English), Frontiers in Bioengineering and Biotechnology, vol. 10, Mar 25 2022.
• [24] S. Najafi-Soulari, H. Shekarchizadeh, M. Kadivar, "Encapsulation optimization of lemon balm antioxidants in calcium alginate hydrogels," Journal of Biomaterials science, Polymer edition, vol. 27, no. 16, pp. 1631-1644, 2016.
• [25] S. Jabeen, M. Maswal, O. A. Chat, G. M. Rather, A. A. Dar, "Rheological behavior and Ibuprofen delivery applications of pH responsive composite alginate hydrogels," Colloids and Surfaces B: Biointerfaces, vol. 139, pp. 211-218, 2016.
• [26] G. Lawrie, I. Keen, B. Drew, A. Chandler-Temple, L. Rintoul, P. Fredericks, L. Grøndahl, "Interactions between alginate and chitosan biopolymers characterized using FTIR and XPS," Biomacromolecules, vol. 8, no. 8, pp. 2533-2541, 2007.
• [27] Q. Yao, P. Nooeaid, J. A. Roether, Y. Dong, Q. Zhang, A. R. Boccaccini, "Bioglass®-based scaffolds incorporating polycaprolactone and chitosan coatings for controlled vancomycin delivery," Ceramics International, vol. 39, no. 7, pp. 7517-7522, 2013.
• [28] A. Kaur, D. Goyal, R. Kumar, "Surfactant mediated interaction of vancomycin with silver nanoparticles," Applied Surface Science, vol. 449, pp. 23-30, 2018.
• [29] F. Hajiahmadi, M. Y. Alikhani, H. Shariatifar, M. R. Arabestani, D. Ahmadvand, "The bactericidal effect of liposomal vancomycin as a topical combating system against Methicillin-resistant Staphylococcus aureus skin wound infection in mice," Medical Journal of the Islamic Republic of Iran, vol. 33, p. 153, 2019.
• [30] H. Miyake, D. Miyazaki, Y. Shimizu, S.I. Sasaki, T. Baba, Y. Inoue, K. Matsuura, "Toxicities of and inflammatory responses to moxifloxacin, cefuroxime, and vancomycin on retinal vascular cells" (in English), Scientific Reports, vol. 9, Jul 5 2019.
• [31] R. G. Finch, D. Greenwood, R. J. Whitley, S. R. Norrby, Antibiotic and chemotherapy e-book. Elsevier Health Sciences, 2010.
• [32] J. Pauwels I. Spriet, X. Fu, S. Von Winckelmann, L. Willems, J. Hoogmartens, A. V. Schepdael, "Chemical Stability and Compatibility Study of Vancomycin for Administration by Continuous Infusion in Intensive Care Units," Journal of liquid chromatography & related technologies, vol. 34, no. 17, pp. 1965-1975, 2011.
• [33] M. Schafer, T. R. Schneider, G. M. Sheldrick, "Crystal structure of vancomycin," (in English), Structure, vol. 4, no. 12, pp. 1509-1515, Dec 15 1996.