IN VIVO BIOCOMPATIBILITY EVALUATION OF NORFLOXACIN-LOADED CHITOSAN NANOFIBERS AND BORONIC ALDEHYDE-FUNCTIONALIZED DERIVATIVES IN RAT

Authors

  • C. I. FOIA Grigore T. Popa University of Medicine and Pharmacy Iasi, Romania
  • C. G. COMAN Grigore T. Popa University of Medicine and Pharmacy Iasi, Romania
  • Caroline CHABOT Université Catholique de Louvain, Cliniques Universitaires Saint-Luc, Bruxelles, Belgium
  • I. GARDIKIOTIS Grigore T. Popa University of Medicine and Pharmacy Iasi, Romania
  • Mioara TRANDAFIRESCU Grigore T. Popa University of Medicine and Pharmacy Iasi, Romania
  • Liliana Lăcrămioara PAVEL Dunarea de Jos University, Galati, Romania, Faculty of Medicine and Pharmacy
  • P. D. SÎRBU Grigore T. Popa University of Medicine and Pharmacy Iasi, Romania
  • Liliana MITITELU-TARTAU Grigore T. Popa University of Medicine and Pharmacy Iasi, Romania
  • T. VOLOSENIUC Grigore T. Popa University of Medicine and Pharmacy Iasi, Romania

DOI:

https://doi.org/10.22551/MSJ.2026.02.14

Abstract

Chitosan-based nanofibers can serve as carriers for antimicrobial agents, providing controlled drug release and biocompatibility, which are crucial for tissue integration and healing. This study aimed to evaluate the in vivo biocompatibility of norfloxacin-loaded chitosan nanofibers (NorC) and norfloxacin-loaded chitosan nanofibers functionalized with boronic aldehyde (NorCB), in comparison with standard wound treatments in rats. Materials and methods: NorC fibers were prepared via electrospinning of chitosan (CHIT) solution containing norfloxacin (Nor). NorCB fibers were obtained by imination of NorC fibers with boronic aldehyde. The study included four groups of Wistar rats: (i) a negative control group, which remained intact with no procedures performed, (ii) a positive control group with a simple incision covered by sulfadiazine-impregnated dressing as a clinically established reference for local antimicrobial protection, and (iii and iv) experimental groups with an incision covered by NorC, respectively NorCB nanoporous fibers. Biocompatibility was evaluated through clinical monitoring, as well as hematological, biochemical, and immunological blood analyses. All procedures were performed in compliance with institutional ethical guidelines for animal experimentation. Results: Both NorC and NorCB fibers did not impair liver or kidney function, did not induce local or systemic inflammatory responses, and preserved immune defense capacity. Laboratory parameters evaluated were comparable with those of the control groups. Functionalization with boronic aldehyde had no adverse impact on these outcomes. Conclusions: Nor-loaded CHIT nanofibers, with or without boronic agent functionalization, demonstrate good in vivo biocompatibility, maintaining organ function, immune competence, and absence of inflammatory effects. These findings support their potential as localized antibiotic delivery systems and advanced wound care materials.

References

1. Cartotto R, Johnson LS, Savetamal A, et al. American burn association clinical practice guidelines on burn shock resuscitation. J Burn Care Res 2024; 45(3): 565-589.

2. Roy S, Mukherjee P, Kundu S, Majumder D, Raychaudhuri V, Choudhury L. Microbial infections in burn patients. Acute Crit Care 2024; 39(2): 214-225.

3. Siu WS, Ma H, Leung PC. Review on current advancements in facilitation of burn wound healing. Bioengineering (Basel) 2025; 12(4): 428.

4. Garcia Garcia JA, Gonzalez Chavez AM, Orozco Grados JJ. Topical antimicrobial agents for the prevention of burn-wound infection. What do international guidelines recommend? A systematic review. World J Plast Surg 2022; 11(3): 3-12.

5. De Clercq A, Vervalcke J, De Petter C, et al. Pharmacokinetics and target attainment of fluoro-quinolones in older adults: a systematic review. Clin Pharmacokinet 2025; 65: 27-69.

6. Fàbrega A, Madurga S, Giralt E, Vila J. Mechanism of action of and resistance to quinolones. Microb Biotechnol 2009; 2(1): 40-61.

7. Dalhoff A. Global fluoroquinolone resistance epidemiology and implications for clinical use. Interdiscip Perspect Infect Dis 2012; 2012: 976273.

8. Jin SG. Recent applications of chitosan-based biomaterials as wound dressings. Int J Mol Sci 2026; 27(4): 1637.

9. Petroni S, Tagliaro I, Antonini C, et al. Chitosan-based biomaterials: insights into chemistry, properties, devices, and their biomedical applications. Mar Drugs 2023; 21(3): 147

10. Taokaew S, Chuenkaek T. Developments of core/shell chitosan-based nanofibers by electrospinning techniques: a review. Fibers 2024; 12(3): 26.

11. Balakrishnan P, Mohanty M, Umashankar PR, Jayakrishnan A. Evaluation of an in situ forming hydrogel wound dressing based on oxidized alginate and gelatin. Biomacromolecules 2013; 14(3): 822 830.

12. Ferraz MP. Wound dressing materials: bridging material science and clinical practice. Appl Sci 2025; 15(4): 1725.

13. Boateng JS, Catanzano O. Advanced therapeutic dressings for effective wound healing - A review. J Pharm Sci 2015; 104(11): 3653-3680.

14. Anisiei A, Andreica BI, Mititelu-Tartau L, et al. Biodegradable trimethyl chitosan nanofiber mats by electrospinning as bioabsorbable dressings for wound closure and healing. Int J Biol Macromol 2023; 249: 126056.

15. https://legislatie.just.ro/Public/DetaliiDocument/52457. Accessed 1.02.2026.

16. https://eur-lex.europa.eu/eli/dir/2010/63/oj. Accessed 1.02.2026.

17. Coman CG, Anisiei A, Cibotaru S, et al. Chitosan electrospun fibers encapsulating norfloxacin: The impact on the biochemical, oxidative and immunological profile in a rat burn model. Int J Mol Sci 2024; 25(23): 12709.

18. Ailincai D, Cibotaru S, Anisiei A, et al. Mesoporous chitosan nanofibers loaded with norfloxacin and coated with phenylboronic acid perform as bioabsorbable active dressings to accelerate the healing of burn wounds. Carbohydr Polym 2023; 318: 121135.

19. Cibotaru S, Anisiei A, Platon VM, et al. Imino quaternized chitosan/chitosan nanofibers loaded with norfloxacin as potential bandages for wound healing. Int J Biol Macromol 2025; 314: 144304.

20. Bagheri M, Validi M, Gholipour A, et al. Chitosan nanofiber biocomposites for potential wound healing applications: Antioxidant activity with synergic antibacterial effect. Bioeng Transl Med 2021; 7(1): e10254.

21. Faccendini A, Ruggeri M, Miele D, et al. Norfloxacin loaded electrospun scaffolds: Montmorillonite nanocomposite vs. free drug. Pharmaceutics 2020; 12(4): 325.

22. Mahmoud AA, Salama AH. Norfloxacin-loaded collagen/chitosan scaffolds for skin reconstruction: Preparation, evaluation and in-vivo wound healing assessment. Eur J Pharm Sci 2016; 83: 155-65.

23. Cheng Y, Wang J, Hu Z, et al. Preparation of norfloxacin-grafted chitosan antimicrobial sponge and its application in wound repair. Int J Biol Macromol 2022; 210: 243-251.

24. Ali SH, Mahammed MA, Yasin SA. Characterization of electrospinning chitosan nanofibers used for wound dressing. Polymers 2024; 16(14): 1984.

25. Kumar V, Sharma N, Janghu P, et al. Synthesis and characterization of chitosan nanofibers for wound healing and drug delivery application. J Drug Deliv Sci Technol 2023; 104858.

Additional Files

Published

2026-06-01