Document Type : Short Communication


1 Department of Comparative Biosciences, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran

2 Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran


Sustained release drug formulations are frequently developed to reduce dosage frequency and to improve outcomes of drug therapy. This study evaluates the pharmacokinetic (PK) parameters of a novel injectable danofloxacin (DANO) formulation in comparison with a conventional product in an animal model. A recently synthesized DANO formulation, prepared by incorporation of DANO-loaded mesoporous silica nanoparticles in liposomes and integration of liposomes in chitosan and β-glycerophosphate solution (lipogel) along with the conventional DANO product were injected subcutaneously (SC) in rabbits. Blood samples were collected at specific time points and DANO concentrations in plasma samples were measured. The PK parameters including maximum concentration (Cmax), time to reach Cmax (Tmax), area under the concentrationversustime curves (AUC), area under the first moment concentration-time curve (AUMC) and mean residence time (MRT) were studied by non-compartmental analyses. The values of MRT (156.00 ± 20.00 hr), AUC (15.30 ± 3.00 µg mL-1 perhr) and Tmax (4.70 ± 1.60 hr) for lipogel formulation were higher than those of the conventional product (8.50 ± 3.60 hr, 3.70 ± 2.00 µg mL-1 per hr and 0.80 ± 0.26 hr, respectively). However, Cmax values for lipogel formulation (0.41 ± 0.15 µg mL-1) were significantly lower than those of the conventional drug product (0.68 ± 0.09 µg mL-1). It was concluded that the novel DANO lipogel effectively slowed down the drug absorption and the incorporation of liposomes in hydrogel could be a useful approach to maintain the therapeutic drug level for a longer period; however, more studies are needed in this field.


  1. Medlicott NJ, Waldron NA, Foster TP. Sustained release veterinary parenteral products. Adv Drug Deliv Rev 2004; 56(10):1345-1365.
  2. Rathbone MJ. Delivering drugs to farmed animals using controlled release science and technology. Int J Sci Med Edu 2012; 6: S118-S128.
  3. Balamurugan M. Chitosan: a perfect polymer used in fabricating gene delivery and novel drug delivery system. Int J Pharm Pharm Sci 2012; 4(3): 54-56.
  4. Mohseni M, Gilani K, Mortazavi SA. Preparation and characterization of rifampin loaded mesoporous silica nanoparticles as a potential system for pulmonary drug delivery. Iran J Pharm Res 2015; 14(1):27-34.
  5. Yang F, Sun N, Liu YM, et al. Estimating danofloxacin withdrawal time in broiler chickens based on physiologically based pharmacokinetics modeling. J Vet Pharmacol Ther 2015; 38(2):174-182.
  6. Kiani K, Rassouli A, Hosseinzadeh Ardakani Y, et al. Preparation and evaluation of a thermosensitive liposomal hydrogel for sustained delivery of dano-floxacin using mesoporous silica nanoparticles. Iran J Vet Med 2016; 10(4):295-305.
  7. Ruel-Gariépy E, Leclair G, Hildgen P, et al. Thermosensitive chitosan-based hydrogel containing liposomes for the delivery of hydrophilic molecules. J Control Release 2002; 82(2-3):373-383.
  8. Shashi K, Satinder K, Bharat P. Complete review on liposomes. Int Res J Pharm 2012; 3(7):10-16.
  9. Mulik R, Kulkarni V, Murthy RSR. Chitosan-based thermosensitive hydrogel containing liposomes for sustained delivery of cytarabine. Drug Dev Ind Pharm 2009; 35(1):49-56.
  10. McKellar Q, Gibson I, Monteiro A, et al. Pharmacokinetics of enrofloxacin and danofloxacin in plasma, inflammatory exudate, and bronchial secretions of calves following subcutaneous administration. Anti-microb Agents Chemother 1999; 43(8): 1988-1992.
  11. Xiao X, Pei L, Jiang LJ, et al. In vivo pharmaco-kinetic/pharmacodynamic profiles of danofloxacin in rabbits infected with salmonella typhimurium after oral administration. Front Pharmacol 2018; 9:391. doi: 10.3389/fphar.2018.00391.
  12. Fernández-Varón E, Marin P, Escudero E, et al. Pharmacokinetic-pharmacodynamic integration of danofloxacin after intravenous, intramuscular and subcutaneous administration to rabbits. J Vet Pharmacol Ther 2007; 30(1): 18-24.
  13. Baggot JD, Giguère S. Principles of antimicrobial drug bioavailability and disposition. In: Giguère S, Prescott JF, Dowling PM (Eds). Antimicrobial therapy in veterinary medicine. 5th ed. Iowa, USA: Wiley-Blackwell 2013; 41-78.
  14. Sárközy G. Quinolones: a class of antimicrobial agents. Vet Med -Czech 2001; 46 (9–10): 257-274.
  15. Saikia C, Gogoi P, Maji TK. Chitosan: a promising biopolymer in drug delivery applications. J Mol Genet Med 2015; S4-006. doi:10.4172/1747-0862.S4-006.
  16. Shi Y, Zhang X, Li J, et al. Preparation and pharmacokinetics of an injectable thermosensitive hydrogel of diminazene aceturate. J Drug Deliv Sci Technol 2013; 23(6): 531-535.
  17. Geng ZX, Li H-M, Tian J, et al. Study of pharmacokinetics of an in situ forming gel system for controlled delivery of florfenicol in pigs. J Vet Pharmcol Ther 2015; 38(6): 596-600.
  18. Elmas M, Yazar E, Baş AL, et al. Comparative pharmaco-kinetics of enrofloxacin and tissue concentrations of parent drug and ciprofloxacin after intramuscular administrations of free and liposome-encapsulated enrofloxacin in rabbits. J Vet Med B Infect Dis Vet Public Health 2002; 49(10): 507-512.
  19. Marshall BM, Levy SB. Food animals and anti-microbials: impacts on human health. Clin Microbiol Rev 2011; 24(4): 718-733.