Gentamicin Release from Hydroxyapatite-based Bioceramic Coating on Titanium
DOI:
https://doi.org/10.18485/Keywords:
Coatings, Bioceramics, Hydroxyapatite, Titanium, Gentamicin, Diffusion, ModelingAbstract
Novel antibacterial bioceramic hydroxyapatite/poly(vinyl alcohol)/chitosan/gentamicin (HAP/PVA/CS/Gent) coating on titanium substrate was successfully produced for bone tissues implants, to enable a drug delivery directly at the infection site and avoid the systemic antibiotic administration in the case of post-operative hospital infections. This study represents novel two compartmental model with General fractional derivative of distributed order used to investigate the release of gentamicin in surrounding tissue. The gentamicin release profile was represented as time dependence of ratio between mass of released gentamicin, determined by high-performance liquid chromatography (HPLC), and initial mass of gentamicin in the coating. It has been proved that proposed a two compartmental model with General fractional derivative of distributed order exhibited excellent agreement between experimental values and calculated values from the model, and enabled the determination of gentamicin diffusion coefficient in entire time period.
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Abdulghani, S., & Mitchell, G. R. (2019). Biomaterials for in situ tissue regeneration: A review. Biomolecules, 9(11). https://doi.org/10.3390/biom9110750
Atanackovic, T. M., Pilipovic, S., Stankovic, B., & Zorica, D. (2014). Fractional Calculus with applications in Mechanics: Vibrations and Diffusion Processes. ISTE, London, John Wiley & Sons, New York.
Atanackovic, T. M., Radojević, V., Petrović, M., & Mišković Stanković, V. (2025). Model of Stress–Strain Dependence for Poly(Vinyl Alcohol)-Based Hydrogels. Polymer Engineering and Science, 4573–4580. https://doi.org/10.1002/pen.27275
Brezinski, C. (2007). NUMERICAL METHODS FOR LAPLACE TRANSFORM INVERSION. Springer Science Business.
Chouirfa, H., Bouloussa, H., Migonney, V., & Falentin-Daudré, C. (2019). Review of titanium surface modification techniques and coatings for antibacterial applications. Acta Biomaterialia, 83, 37–54. https://doi.org/10.1016/j.actbio.2018.10.036
Churilov, A., Medvedev, A., & Shepeljavyi, A. (2009). Mathematical model of non-basal testosterone regulation in the male by pulse modulated feedback. Automatica, 45(1), 78– 85.
https://www.sciencedirect.com/science/article/abs/pii/S00051 09808003890?via%3Dihub
Copot, D., & Ionescu, C. M. (2014). Drug delivery system for general anesthesia: Where are we? Conference Proceedings - IEEE International Conference on Systems, Man and Cybernetics, 2014-Janua(January), 2452–2457. https://doi.org/10.1109/smc.2014.6974294
Copot, D., Magin, R. L., De Keyser, R., & Ionescu, C. (2017). Data- driven modelling of drug tissue trapping using anomalous kinetics. Chaos, Solitons and Fractals, 102, 441–446. https://doi.org/10.1016/j.chaos.2017.03.031
Dokoumetzidis, A., & MacHeras, P. (2009). Fractional kinetics in drug absorption and disposition processes. Journal of Pharmacokinetics and Pharmacodynamics, 36(2), 165–178. https://doi.org/10.1007/s10928-009-9116-x
Dokoumetzidis, A., Magin, R., & Macheras, P. (2010). A commentary on fractionalization of multi-compartmental models. Journal of Pharmacokinetics and Pharmacodynamics, 37(2), 203–207. https://doi.org/10.1007/s10928-010-9153-5
Drexler, D. A., Kovács, L., Sápi, J., Harmati, I., & Benyó, Z. (2011). Model-based analysis and synthesis of tumor growth under angiogenic inhibition: a case study. IFAC Proceedings Volumes, 44(1), 3753–3758.
https://doi.org/10.3182/20110828-6-IT-1002.02107
Fiume, E., Magnaterra, G., Rahdar, A., Verné, E., & Baino, F. (2021). Hydroxyapatite for biomedical applications: A short overview. Ceramics, 4(4), 542–563. https://doi.org/10.3390/ceramics4040039
Ionescu, C., Lopes, A., Copot, D., Machado, J. A. T., & Bates, J. H.
T. (2017). The role of fractional calculus in modeling biological phenomena: A review. Communications in Nonlinear Science and Numerical Simulation, 51, 141–159. https://www.sciencedirect.com/science/article/abs/pii/S10075 70417301119?via%3Dihub
Ionescu, C. M., Copot, D., & De Keyser, R. (2017). Anesthesiologist in the Loop and Predictive Algorithm to Maintain Hypnosis While Mimicking Surgical Disturbance. IFAC-PapersOnLine, 50(1), 15080–15085.
https://www.sciencedirect.com/science/article/pii/S24058963 1733447X?via%3Dihub
Kaur, M., & Singh, K. (2019). Review on titanium and titanium based alloys as biomaterials for orthopaedic applications. 102(December 2018), 844–862.
https://www.sciencedirect.com/science/article/pii/S09284931 18338232
Kiss, B., Sápi, J., & Kovács, L. (2013). Imaging method for model- based control of tumor diseases. SISY 2013 - IEEE 11th International Symposium on Intelligent Systems and Informatics, Proceedings, October 2015, 271–275. https://doi.org/10.1109/SISY.2013.6662584
Kovács, L., Benyó, B., Bokor, J., & Benyó, Z. (2011). Induced L2- norm minimization of glucose–insulin system for Type I diabetic patients. Computer Methods and Programs in Biomedicine, 102(2), 105–118. https://doi.org/10.1016/J.CMPB.2010.06.019
Mahanty, A., & Shikha, D. (2022). Changes in the morphology, mechanical strength and biocompatibility of polymer and metal/polymer fabricated hydroxyapatite for orthopaedic implants: A review. Journal of Polymer Engineering, 42(4), 298–322. https://doi.org/10.1515/polyeng-2021-0171
Masters, E. A., Trombetta, R. P., de Mesy Bentley, K. L., Boyce, B. F., Gill, A. L., Gill, S. R., Nishitani, K., Ishikawa, M., Morita,
Y., Ito, H., Bello-Irizarry, S. N., Ninomiya, M., Brodell, J. D.,
Lee, C. C., Hao, S. P., Oh, I., Xie, C., Awad, H. A., Daiss, J.
L., … Muthukrishnan, G. (2019). Evolving concepts in bone infection: redefining “biofilm”, “acute vs. chronic osteomyelitis”, “the immune proteome” and “local antibiotic therapy.” Bone Research, 7(1). https://doi.org/10.1038/s41413-019-0061-z
Mišković-Stanković, V., & Atanackovic, T. (2024). Novel antibacterial biomaterials for medical applications and modeling of drug release process. In Novel Antibacterial Biomaterials for Medical Applications and Modeling of Drug Release Process. https://doi.org/10.1201/9781032668895
Miskovic-Stankovic, V., & Atanackovic, T. M. (2023). On a System of Equations with General Fractional Derivatives Arising in Diffusion Theory. Fractal and Fractional, 7(7), 1–13. https://doi.org/10.3390/fractalfract7070518
Miskovic-Stankovic, V., Janev, M., & Atanackovic, T. M. (2023). Two compartmental fractional derivative model with general fractional derivative. Journal of Pharmacokinetics and Pharmacodynamics, 50(2), 79–87.
https://doi.org/10.1007/s10928-022-09834-8
Mišković-Stanković, V., Janković, A., Grujić, S., Matić-Bujagić, I., Radojević, V., Vukašinović-Sekulić, M., Kojić, V., Djošić, M., & Atanacković, T. M. (2024). Diffusion models of gentamicin released in poly(vinyl alcohol)/chitosan hydrogel. Journal of the Serbian Chemical Society, 89(5), 627–641. https://doi.org/10.2298/JSC231207010M
Mišković-Stanković, V., Stevanović, M., & Atanackovic, T. M. (2025). Bioceramic coatings electrodeposited on titanium surface aimed for medical applications. Journal of Solid State Electrochemistry, 0123456789.
https://doi.org/10.1007/s10008-025-06368-0
Podlubny, I. (1999). Fractional Differential Equations. Academic Press, San Diego.
Popović, J. K., Atanacković, M. T., Pilipović, A. S., Rapaić, M. R., Pilipović, S., & Atanacković, T. M. (2010). A new approach to the compartmental analysis in pharmacokinetics: Fractional time evolution of diclofenac. Journal of Pharmacokinetics and Pharmacodynamics, 37(2), 119–134. https://doi.org/10.1007/s10928-009-9147-3
Popović, J. K., Dolićanin, D., Rapaić, M. R., Popović, S. L., Pilipović, S., & Atanacković, T. M. (2011). A nonlinear two compartmental fractional derivative model. European Journal of Drug Metabolism and Pharmacokinetics, 36(4), 189–196. https://doi.org/10.1007/s13318-011-0057-6
Popović, J. K., Spasić, D. T., Tošić, J., Kolarović, J. L., Malti, R., Mitić, I. M., Pilipović, S., & Atanacković, T. M. (2015). Fractional model for pharmacokinetics of high dose methotrexate in children with acute lymphoblastic leukaemia. Communications in Nonlinear Science and Numerical Simulation, 22(1–3), 451–471. https://www.sciencedirect.com/science/article/abs/pii/S10075 70414003979?via%3Dihub
Rajšić, I., Lazarević, S., Đanić, M., Al-Salami, H., Mooranian, A., Vukmirović, S., Mikov, M., & Goločorbin-Kon, S. (2022). Plasma Distribution of Methotrexate and Its Polyglutamates in Pediatric Acute Lymphoblastic Leukemia: Preliminary Insights. European Journal of Drug Metabolism and Pharmacokinetics, 47(1), 127–134.
Raut, H. K., Das, R., Liu, Z., Liu, X., & Ramakrishna, S. (2020). Biocompatibility of Biomaterials for Tissue Regeneration or Replacement. Biotechnology Journal, 15(12), 1–14. https://doi.org/10.1002/biot.202000160
Rescigno, A. (2003). Foundations of Pharmacokinetics. Springer New York, NY. https://doi.org/https://doi.org/10.1007/b105300
Samko, S. G., & Cardoso, R. P. (2003). Integral equations of the first kind of Sonine type. International Journal of Mathematics and Mathematical Sciences, 2003(57), 3609–3632. https://doi.org/10.1155/S0161171203211455
Sopasakis, P., Sarimveis, H., Macheras, P., & Dokoumetzidis, A. (2018). Fractional calculus in pharmacokinetics. Journal of Pharmacokinetics and Pharmacodynamics, 45(1), 107–125. https://doi.org/10.1007/s10928-017-9547-8
Stepanovska, J., Matejka, R., Rosina, J., Bacakova, L., & Kolarova,
H. (2020). Treatments for enhancing the biocompatibility of titanium implants. Biomedical Papers, 164(1), 23–33. https://doi.org/10.5507/bp.2019.062
Stevanović, M., Djošić, M., Janković, A., Kojić, V., Stojanović, J., Grujić, S., Bujagić, I. M., Rhee, K. Y., & Mišković-Stanković,
V. (2021). The chitosan-based bioactive composite coating on titanium. Journal of Materials Research and Technology, 15, 4461–4474.
https://www.sciencedirect.com/science/article/pii/S22387854 21012102
Stevanović, M., Djošić, M., Janković, A., Kojić, V., Vukašinović- Sekulić, M., Stojanović, J., Odović, J., Crevar Sakač, M., Kyong Yop, R., & Mišković-Stanković, V. (2020). Antibacterial graphene-based hydroxyapatite/chitosan coating with gentamicin for potential applications in bone tissue engineering. Journal of Biomedical Materials Research - Part A, 108(11), 2175–2189. https://doi.org/10.1002/jbm.a.36974
Stevanović, M., Djošić, M., Janković, A., Nešović, K., Kojić, V., Stojanović, J., Grujić, S., Matić Bujagić, I., Rhee, K. Y., & Mišković-Stanković, V. (2020). Assessing the bioactivity of gentamicin-preloaded hydroxyapatite/Chitosan composite coating on titanium substrate. ACS Omega, 5(25), 15433– 15445. https://doi.org/10.1021/acsomega.0c01583
Stevanović, M., Đošić, M., Janković, A., Kojić, V., Vukašinović- Sekulić, M., Stojanović, J., Odović, J., Crevar Sakač, M., Rhee,
K. Y. Y. Y., & Mišković-Stanković, V. (2018). Gentamicin- Loaded Bioactive Hydroxyapatite/Chitosan Composite Coating Electrodeposited on Titanium. ACS Biomaterials Science and Engineering, 4(12), 3994–4007. https://doi.org/10.1021/acsbiomaterials.8b00859
Tarasov, V. E. (2021). General fractional dynamics. Mathematics, 9(13), 1–26. https://doi.org/10.3390/math9131464
Verotta, D. (2010). Fractional compartmental models and multi-term Mittag-Leffler response functions. Journal of Pharmacokinetics and Pharmacodynamics, 37(2), 209–215. https://doi.org/10.1007/s10928-010-9155-3
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