Journal of Veterinary Science

The Korean Society of Veterinary Science (대한수의학회)
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Antibacterial activity of florfenicol composite nanogels against Staphylococcus aureus small colony variants

  • Liu, Jinhuan (Engineering Laboratory for Tarim Animal Diseases Diagnosis and Control, College of Animal Science, Tarim University) ;
  • Ju, Mujie (Engineering Laboratory for Tarim Animal Diseases Diagnosis and Control, College of Animal Science, Tarim University) ;
  • Wu, Yifei (Engineering Laboratory for Tarim Animal Diseases Diagnosis and Control, College of Animal Science, Tarim University) ;
  • Leng, Nannan (Engineering Laboratory for Tarim Animal Diseases Diagnosis and Control, College of Animal Science, Tarim University) ;
  • Algharib, Samah Attia (Department of Clinical Pathology, Faculty of Veterinary Medicine, Benha University) ;
  • Luo, Wanhe (Engineering Laboratory for Tarim Animal Diseases Diagnosis and Control, College of Animal Science, Tarim University)
  • Received : 2022.03.04
  • Accepted : 2022.08.02
  • Published : 2022.09.30
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Abstract

Background: Florfenicol might be ineffective for treating Staphylococcus aureus small colony variants (SCVs) mastitis. Objectives: In this study, florfenicol-loaded chitosan (CS)-sodium tripolyphosphate (TPP) composite nanogels were prepared to allow targeted delivery to SCV infected sites. Methods: The formulation screening, the characteristics, in vitro release, antibacterial activity, therapeutic efficacy, and biosafety of the florfenicol composite nanogels were studied. Results: The optimized formulation was obtained when the CS and TPP were 10 and 5 mg/mL, respectively. The encapsulation efficiency, loading capacity, size, polydispersity index, and zeta potential of the optimized florfenicol composite nanogels were 87.3% ± 2.7%, 5.8% ± 1.4%, 280.3 ± 1.5 nm, 0.15 ± 0.03, and 36.3 ± 1.4 mv, respectively. Optical and scanning electron microscopy showed that spherical particles with a relatively uniform distribution and drugs might be incorporated in cross-linked polymeric networks. The in vitro release study showed that the florfenicol composite nanogels exhibited a biphasic pattern with the sustained release of 72.2% ± 1.8% at 48 h in pH 5.5 phosphate-buffered saline. The minimal inhibitory concentrations of commercial florfenicol solution and florfenicol composite nanogels against SCVs were 1 and 0.25 ㎍/mL, respectively. The time-killing curves and live-dead bacterial staining showed that the florfenicol composite nanogels were concentration-dependent. Furthermore, the florfenicol composite nanogels displayed good therapeutic efficacy against SCVs mastitis. Biological safety studies showed that the florfenicol composite nanogels might be a biocompatible preparation because of their non-toxic effects on the renal tissue and liver. Conclusions: Florfenicol composite nanogels might improve the treatment of SCV infections.

Keywords

Acknowledgement

The article is financially supported by the President fund of Tarim University (TDZKSS202144) and the Program for Young and Middle-aged Technology Innovation Leading Talents (2019CB029).

References

  1. Fung-Tomc J, Kolek B, Bonner DP. Ciprofloxacin-induced, low-level resistance to structurally unrelated antibiotics in Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother. 1993;37(6):1289-1296. https://doi.org/10.1128/AAC.37.6.1289
  2. Sommerhauser J, Kloppert B, Wolter W, Zschock M, Sobiraj A, Failing K. The epidemiology of Staphylococcus aureus infections from subclinical mastitis in dairy cows during a control programme. Vet Microbiol. 2003;96(1):91-102. https://doi.org/10.1016/S0378-1135(03)00204-9
  3. Algharib SA, Dawood A, Xie S. Nanoparticles for treatment of bovine Staphylococcus aureus mastitis. Drug Deliv. 2020;27(1):292-308. https://doi.org/10.1080/10717544.2020.1724209
  4. Foster TJ. The Staphylococcus aureus "superbug". J Clin Invest. 2004;114(12):1693-1696. https://doi.org/10.1172/JCI200423825
  5. Zhou K, Li C, Chen D, Pan Y, Tao Y, Qu W, et al. A review on nanosystems as an effective approach against infections of Staphylococcus aureus. Int J Nanomedicine. 2018;13:7333-7347. https://doi.org/10.2147/IJN.S169935
  6. Luo W, Liu J, Zhang S, Song W, Algharib SA, Chen W. Enhanced antibacterial activity of tilmicosin against Staphylococcus aureus small colony variants by chitosan oligosaccharide-sodium carboxymethyl cellulose composite nanogels. J Vet Sci. 2022;23(1):e1. https://doi.org/10.4142/jvs.21208
  7. von Eiff C, Becker K, Metze D, Lubritz G, Hockmann J, Schwarz T, et al. Intracellular persistence of Staphylococcus aureus small-colony variants within keratinocytes: a cause for antibiotic treatment failure in a patient with Darier's disease. Clin Infect Dis. 2001;32(11):1643-1647. https://doi.org/10.1086/320519
  8. Blickwede M, Valentin-Weigand P, Rohde M, Schwarz S. Effects of subinhibitory concentrations of florfenicol on morphology, growth, and viability of Staphylococcus aureus. J Vet Med B Infect Dis Vet Public Health. 2004;51(6):293-296. https://doi.org/10.1111/j.1439-0450.2004.00767.x
  9. Smith GW, Gehring R, Craigmill AL, Webb AI, Riviere JE. Extralabel intramammary use of drugs in dairy cattle. J Am Vet Med Assoc. 2005;226(12):1994-1996. https://doi.org/10.2460/javma.2005.226.1994
  10. Algharib SA, Dawood A, Zhou K, Chen D, Li C, Meng K, et al. Designing, structural determination and biological effects of rifaximin loaded chitosan- carboxymethyl chitosan nanogel. Carbohydr Polym. 2020;248:116782. https://doi.org/10.1016/j.carbpol.2020.116782
  11. Liu J, Ju M, Guan D, Song W, Algharib S, Luo W. Composite inclusion complexes containing sodium alginate composite nanogels for pH-responsive valnemulin hydrochloride release. J Mol Struct. 2022;1263:133054. https://doi.org/10.1016/j.molstruc.2022.133054
  12. Liu Y, Chen D, Zhang A, Xiao M, Li Z, Luo W, et al. Composite inclusion complexes containing hyaluronic acid/chitosan nanosystems for dual responsive enrofloxacin release. Carbohydr Polym. 2021;252:117162. https://doi.org/10.1016/j.carbpol.2020.117162
  13. Kalam MA. The potential application of hyaluronic acid coated chitosan nanoparticles in ocular delivery of dexamethasone. Int J Biol Macromol. 2016;89:559-568. https://doi.org/10.1016/j.ijbiomac.2016.05.016
  14. Algharib S, Dawood A, Zhou K, Chen D, Li C, Meng K, et al. Preparation of chitosan nanoparticles by ionotropic gelation technique: effects of formulation parameters and in vitro characterization. J Mol Struct. 2022;1252:132129. https://doi.org/10.1016/j.molstruc.2021.132129
  15. Ikram R, Mohamed Jan B, Abdul Qadir M, Sidek A, Stylianakis MM, Kenanakis G. Recent advances in chitin and chitosan/graphene-based bio-nanocomposites for energetic applications. Polymers (Basel). 2021;13(19):3266. https://doi.org/10.3390/polym13193266
  16. Agnihotri SA, Mallikarjuna NN, Aminabhavi TM. Recent advances on chitosan-based micro- and nanoparticles in drug delivery. J Control Release. 2004;100(1):5-28. https://doi.org/10.1016/j.jconrel.2004.08.010
  17. Muxika A, Etxabide A, Uranga J, Guerrero P, de la Caba K. Chitosan as a bioactive polymer: processing, properties and applications. Int J Biol Macromol. 2017;105(Pt 2):1358-1368. https://doi.org/10.1016/j.ijbiomac.2017.07.087
  18. Wang X, Wang S, Zhang Y. Advance of the application of nano-controlled release system in ophthalmic drug delivery. Drug Deliv. 2016;23(8):2897-2901. https://doi.org/10.3109/10717544.2015.1116025
  19. Sharaf OM, Al-Gamal MS, Ibrahim GA, Dabiza NM, Salem SS, El-Ssayad MF, et al. Evaluation and characterization of some protective culture metabolites in free and nano-chitosan-loaded forms against common contaminants of Egyptian cheese. Carbohydr Polym. 2019;223:115094. https://doi.org/10.1016/j.carbpol.2019.115094
  20. Alkasir R, Liu X, Zahra M, Ferreri M, Su J, Han B. Characteristics of Staphylococcus aureus small colony variant and its parent strain isolated from chronic mastitis at a dairy farm in Beijing, China. Microb Drug Resist. 2013;19(2):138-145. https://doi.org/10.1089/mdr.2012.0086
  21. Wang XF, Zhang SL, Zhu LY, Xie SY, Dong Z, Wang Y, et al. Enhancement of antibacterial activity of tilmicosin against Staphylococcus aureus by solid lipid nanoparticles in vitro and in vivo. Vet J. 2012;191(1):115-120. https://doi.org/10.1016/j.tvjl.2010.11.019
  22. Brakstad OG, Aasbakk K, Maeland JA. Detection of Staphylococcus aureus by polymerase chain reaction amplification of the nuc gene. J Clin Microbiol. 1992;30(7):1654-1660. https://doi.org/10.1128/jcm.30.7.1654-1660.1992
  23. Tong J, Hou X, Cui D, Chen W, Yao H, Xiong B, et al. A berberine hydrochloride-carboxymethyl chitosan hydrogel protects against Staphylococcus aureus infection in a rat mastitis model. Carbohydr Polym. 2022;278:118910. https://doi.org/10.1016/j.carbpol.2021.118910
  24. Suo H, Hussain M, Wang H, Zhou N, Tao J, Jiang H, et al. Injectable and pH-sensitive hyaluronic acid-based hydrogels with on-demand release of antimicrobial peptides for infected wound healing. Biomacromolecules. 2021;22(7):3049-3059. https://doi.org/10.1021/acs.biomac.1c00502
  25. Grimaudo MA, Concheiro A, Alvarez-Lorenzo C. Nanogels for regenerative medicine. J Control Release. 2019;313:148-160. https://doi.org/10.1016/j.jconrel.2019.09.015
  26. van de Manakker F, Vermonden T, van Nostrum CF, Hennink WE. Cyclodextrin-based polymeric materials: synthesis, properties, and pharmaceutical/biomedical applications. Biomacromolecules. 2009;10(12):3157-3175. https://doi.org/10.1021/bm901065f
  27. Zhou K, Wang X, Chen D, Yuan Y, Wang S, Li C, et al. Enhanced treatment effects of tilmicosin against Staphylococcus aureus cow mastitis by self-assembly sodium alginate-chitosan nanogel. Pharmaceutics. 2019;11(10):524. https://doi.org/10.3390/pharmaceutics11100524
  28. Li C, Zhou K, Chen D, Xu W, Tao Y, Pan Y, et al. Solid lipid nanoparticles with enteric coating for improving stability, palatability, and oral bioavailability of enrofloxacin. Int J Nanomedicine. 2019;14:1619-1631. https://doi.org/10.2147/IJN.S183479
  29. Luo W, Qin H, Chen D, Wu M, Meng K, Zhang A, et al. The dose regimen formulation of tilmicosin against Lawsonia intracellularis in pigs by pharmacokinetic-pharmacodynamic (PK-PD) model. Microb Pathog. 2020;147:104389. https://doi.org/10.1016/j.micpath.2020.104389