The Preparation of Liposomal Formulations of Gentamicin and Ceftiofur Used in Veterinary Medicine

Yıl 2023, , 554 - 559, 28.09.2023

Hasan Susar , Murat Çelebi , Çağla Çelebi , Özlem Çoban , Hüseyin Şen , İzzet Karahan

https://doi.org/10.53424/balikesirsbd.1262051

Öz

Objective: The aim of this study is to produce liposomal drugs that are scarcely found in veterinary medicine. Therefore, the current study was designed to produce liposomal formulations of ceftiofur and gentamicin for veterinary use and to perform their quality control studies. Materials and Methods: The Bangham Method was chosen for the preparation of liposomal formulations of gentamicin and ceftiofur. Results: The particle size, polydispersity index and zeta potential were found to be 3934.67 nm, 0.471, -10.3 mV for Ceftiofur-1 coded formulation, 4573.0 nm, 0.308, -9.9 mV for Ceftiofur-2 coded formulation, 479.4 nm, 0.437, -44.8 mV for Ceftiofur-3 coded formulation, respectively. The particle size, polydispersity index and zeta potential were found to be 5185.67 nm, 0.599, -6.5 mV for Gentamicin-1 coded formulation, 4228.0 nm, 0.505, -7.8 mV for Gentamicin-2 coded formulation, 2138.67 nm, 0.565, -6.5 mV for Gentamicin-3 coded formulation, respectively. The encapsulation efficiency of liposomal formulations containing ceftiofur; 82.85%, 95.74%, and 92.06% was found for ceftiofur-1, ceftiofur-2 and ceftiofur 3, respectively. Conclusion: The liposomal formulations of ceftiofur and gentamicin were successfully prepared and their quality control studies were carried out. It was concluded that pharmacokinetic/pharmacodynamic studies should be performed to evaluate the efficacy of liposomal formulations.

Anahtar Kelimeler

Drug, Formulation, Liposome, Veterinary.

Destekleyen Kurum

This research was supported by Balıkesir University Scientific Research Projects Unit

Proje Numarası

2020/095

Teşekkür

We thank the Drugs and Pharmaceutical Technology Application and Research Center of Karadeniz Teknik University and the Balıkesir University Science and Technology Application and Research Center for their support in conducting the study.

Veteriner Hekimlikte Kullanılan Gentamicin ve Seftiofur'un Lipozomal Formülasyonlarının Hazırlanması

Öz

veteriner kullanım için seftiofur ve gentamisinin lipozomal formülasyonlarını üretmek ve kalite kontrol çalışmalarını yapmak hedefleriyle tasarlanmıştır. Gereç ve Yöntem: Gentamisin ve seftiofur’un lipozomal formülasyonlarının hazırlanması amacıyla Bangham Metodu tercih edildi. Bulgular: Sonuç olarak; seftiofur-1 lipozomunun partikül boyutu 3934.67 nm, polidispersite indeksi 0.471, zeta potansiyeli -10.3 mV'dir; Ceftiofur-2 lipozomunda; parçacık boyutu 4573.00 nm, polidispersite indeksi 0.308, zeta potansiyeli -09.9 mV; Ceftiofur-3 lipozomlarında; parçacık boyutu 479.40 nm, polidispersite indeksi 0.437, zeta potansiyeli -44.8 mV ölçülmüştür. Gentamisin-1 lipozomunda; parçacık boyutu 5185.67 nm, polidispersite indeksi 0.599, zeta potansiyeli -06.5 mV; Gentamisin-2 lipozomunda; parçacık boyutu 4228.00 nm, polidispersite indeksi 0.599, zeta potansiyeli -07.8 mV; Gentamisin-3 lipozomunda; parçacık boyutu 2138.67 nm, polidispersite indeksi 0.565, zeta potansiyeli -06.5 mV ölçülmüştür. Sonuç: Seftiofur ve gentamisinin başarılı bir şekilde lipozomal formülasyonları hazırlandı ve kalite kontrol çalışmaları gerçekleştirildi. Lipozomal formülasyonların etkinliklerinin değerlendirilmesi için ise farmakokinetik/farmakodinamik çalışmaların yapılması gerektiği kanaatine varıldı.

Proje Numarası

2020/095

Kaynakça

• Al-Darraji, A., Donahue, R., Tripathi, H., Peng, H., Levitan, B., Chelvarajan, L., Abdel-Latif, A. (2020). Liposomal delivery of azithromycin enhances its immunotherapeutic efficacy and reduces toxicity in myocardial infarction. Scientific Reports, 10. https://doi.org/0.1038/s41598-020-73593-0.
• Ali, B. H., Al Za'abi, M., Blunden, G., & Nemmar, A. (2011). Experimental gentamicin nephrotoxicity and agents that modify it: a mini-review of recent research. Basic & Clinical Pharmacology & Toxicology, 109(4), 225-232. https://doi.org/10.1111/j.17427843.2011.00728.x.
• Bangham, A. D., Standish, M. M., & Watkins, J. C. (1965). Diffusion of univalent ions across the lamellae of swollen phospholipids. Journal of Molecular Biology, 13(1), 238-IN227. https://doi.org/10.1016/S0022-2836(65)80093-6.
• Beltrán-Gracia, E., López-Camacho, A., Higuera-Ciapara, I., Velázquez-Fernández, J. B., & Vallejo-Cardona, A. A. (2019). Nanomedicine review: clinical developments in liposomal applications. Cancer Nanotechnology, 10(1), 11. https://doi.org/10.1186/s12645-019-0055-y.
• Cavanagh, K. (2012). Plumb’s Veterinary Drug Handbook. Pocket-7th edition. The Canadian Veterinary Journal, 53(12), 1284.
• Chou, C. K., Li, Y. C., Chen, S. M., Shih, Y. M., & Lee, J. A. (2015). Chitosan prevents gentamicin-induced nephrotoxicity via a carbonyl stress-dependent pathway. BioMed Research International, 2015, 675714. https://doi.org/10.1155/2015/675714.
• Çoban, Ö., Barut, B., Yalçın, C. Ö., Özel, A., & Bıyıklıoğlu, Z. (2020). Development and in vitro evaluation of BSA-coated liposomes containing Zn (II) phthalocyanine-containing ferrocene groups for photodynamic therapy of lung cancer. Journal of Organometallic Chemistry, 925, 121469. https://doi.org/10.1016/j.jorganchem.2020.121469.
• Çoban, Ö., Yıldırım, S., & Bakır, T. (2021). Alpha-lipoic acid and cyanocobalamin co-loaded nanoemulsions: development, characterization, and evaluation of stability. Journal of Pharmaceutical Innovation. https://doi.org/10.1007/s12247-020-09531-4.
• Gonzalez Gomez, A., Syed, S., Marshall, K., & Hosseinidoust, Z. (2019). Liposomal nanovesicles for efficient encapsulation of staphylococcal antibiotics. ACS Omega, 4(6), 10866-10876. doi:10.1021/acsomega.9b00825.
• Grazia Calvagno, M. C., Christian; Paolino, Donatella; Cosco, Donato; Iannone, Michelangelo; Castelli, Francesco; Doldo, Patrizia; Fresta, Massimo;. (2007). Effects of lipid composition and preparation conditions on physical-chemical properties, technological parameters and in vitro biological activity of gemcitabine-loaded liposomes. Current Drug Delivery, 4(1), 89-101(113).
• Gupta, A., Mumtaz, S., Li, C.-H., Hussain, I., & Rotello, V. M. (2019). Combatting antibiotic-resistant bacteria using nanomaterials. Chemical Society Reviews, 48(2), 415-427. https://doi.org/10.1039/C7CS00748E.
• Hornish, R. E., & Kotarski, S. F. (2002). Cephalosporins in veterinary medicine - ceftiofur use in food animals. Current Topics in Medicinal Chemistry, 2(7), 717-731. https://doi.org/10.2174/1568026023393679.
• Kayaalp, O. (2018). Aminoglikozidler. In O. Kayaalp (Ed.), Akılcıl Tedavi Yönünden Tıbbi Farmakoloji (pp. 233–241). Ankara: Pelikan Yayıncılık.
• Kim, E. M., & Jeong, H. J. (2021). Liposomes: biomedical applications. Chonnam Medical J., 57(1), 27-35. https://doi.org/10.4068/cmj.2021.57.1.27.
• Lasic, D. D. (1998). Novel applications of liposomes. Trends in Biotechnology, 16(7), 307-321. doi:10.1016/s0167-7799(98)01220-7.
• Liu, S., Guo, D., Guo, Y., & Zhou, W. (2011). Preparation and pharmacokinetics of ceftiofur sodium liposomes in cows. Journal of Veterinary Pharmacology and Therapeutics, 34(1), 35-41. https://doi.org/10.1111/j.1365-2885.2010.01190.x.
• Mugabe, C., Azghani, A. O., & Omri, A. (2005). Liposome-mediated gentamicin delivery: development and activity against resistant strains of Pseudomonas aeruginosa isolated from cystic fibrosis patients. Journal of Antimicrobial Chemotherapy, 55(2), 269-271. doi:10.1093/jac/ dkh518.
• Pattni, B. S., Chupin, V. V., & Torchilin, V. P. (2015). New developments in liposomal drug delivery. Chemical Reviews, 115(19), 10938-10966. https://doi.org/10.1021/acs.chemrev.5b00046.
• Saddiqi, M. E., Kadir, A. A., Abdullah, F. F. J., Zakaria, M. Z. A. B., & Banke, I. S. (2022). Preparation, characterization and in vitro cytotoxicity evaluation of free and liposome-encapsulated tylosin. OpenNano, 100108. https://doi.org/10.1016/ j.onano.2022.100108.
• Shen, S., Wu, Y., Liu, Y., & Wu, D. (2017). High drug-loading nanomedicines: progress, current status, and prospects. International Journal of Nanomedicine, 12, 4085-4109. doi:10.2147/ijn.S132780.
• Vilos, C., Constandil, L., Rodas, P. I., Cantin, M., Zepeda, K., Herrera, N., & Velasquez, L. A. (2014). Evaluation of ceftiofur-PHBV microparticles in rats. Drug Design, Development and Therapy, 8, 651-666. https://doi.org/10.2147/dddt.S60444.
• Wagner, K., Vorauer-Uhl, K., & Katinger, H. (2006). Nebulization of liposomal rhcu/zn- Sod with a novel vibrating membrane nebulizer. Journal of Liposome Research, 16, 113–125. https://doi.org/10.1080/08982100600 680733.