THE PROLONGATION OF THE ANTINOCICEPTIVE EFFECTS OF NOVEL NANOSYSTEMS ENTRAPPING DICLOFENAC SODIUM IN SOMATIC PAIN IN RATS
Abstract
The prolongation of the antinociceptive effects of novel nanosystems entrapping diclofenac sodium in somatic pain in rats (Abstract): The aim of this study was the investigation effects of nanosystems incorporating diclofenac sodium on the nociceptive reactivity in rats. Material and methods: In the experimental study were used 24 white healthy, non-genetically modified Wister rats, weighing 200-250 g, with a uniform distribution by sex, purchased from the National Medical-Military Institute “Cantacuzino” for Research and Development, Băneasa, Bucharest. The substances were given orally as follows: Group I (control): distilled water 0.3 mL/100 g body weight, Group 2 (DCF): 5 mg/kg body weight (kbw) diclofenac sodium; Group 3 (DCF-ves): lipid vesicles entrapping diclofenac sodium 5 mg/kbw. The experimental protocol was approved by the University Committee for Research and Ethical Issues, in compliance with the international ethical guidelines regarding the handling of laboratory animals. Data were statistically processed using SPSS software for Windows 17.0 version and ANOVA one-way method. Results: Lipid vesicles containing diclofenac, stabilized with chitosan were designed. The measurements indicated a mean size of 562 nm and a mean Zeta potential of +45 mV, thus suggest a reasonable stability of the colloidal suspension. The use of DCF resulted in a prolongation of the latency period response to thermal noxious tail stimulation, with a statistical significance during 90 minutes in the experiment. The treatment with DCF-ves was accompanied by a substantial increase of the latency time reaction in the interval between 2 hours and 8 hours after the administration. Conclusions: Both entrapped and non-entrapped DCF proved to have an important analgesic effect in tail flick test in rats. The administration of lipid vesicles as carriers for DCF demonstrated a prolonged antinociceptive activity, compared to the non-entrapped drug in this cutaneous pain model in rats.
References
2. Pelaz B, Alexiou C, Alvarez-Puebla RA, et al. Diverse applications of nanomedicine. Acs Nano 2017; 11: 2313-2381.
3. Allahou LW, Madani SY, Seifalian A. Investigating the application of liposomes as drug delivery systems for the diagnosis and treatment of cancer. Int J Biomater 2021; 2021: 3041969.
4. Yu JY, Chuesiang P, Shin GH, Park HJ. Post-processing techniques for the improvement of liposome stability. Pharmaceutics 2021; 13: 1023.
5. Wongrakpanich S, Wongrakpanich A, Melhado K, et al. A comprehensive review of non-steroidal anti-inflammatory drug use in the elderly. Aging Dis 2018; 9(1): 143-150.
6. Gan TJ. Diclofenac: an update on its mechanism of action and safety profile. Curr Med Res Opin 2010; 26(7): 1715-1731.
7. Chuasuwan B, Binjesoh V, Polli JE, et al. Biowaiver monographs for immediate release solid oral dosage forms: diclofenac sodium and diclofenac potassium. J Pharm Sci 2009; 98: 1206-1219.
8. Rainsford KD, Kean WF, Ehrlich GE. Review of the pharmaceutical properties and clinical effects of the topical NSAID formulation, diclofenac epolamine. Curr Med Res Opin 2008; 24(10): 2967-2692.
9. Altman R, Bosch B, Brune K, et al. Advances in NSAID development: evolution of diclofenac products using pharmaceutical technology. Drugs 2015; 75(8): 859-877.
10. Schmidt M, Sørensen HT, Pedersen L. Diclofenac use and cardiovascular risks: series of nationwide cohort studies. BMJ 2018; 362: k3426.
11. Mititelu-Tartau L, Bogdan M, Pricop DA et al. Biocompatibility and pharmacological effects of innovative systems for prolonged drug release containing dexketoprofen in rats. Polymers 2021; 13(1010): 1-14.
12. Mogil J. Animal models of pain: progress and challenges. Nat Rev Neurosci 2009; 10: 283-294.
13. Bannon AW, Malmberg AB. Models of nociception: hot-plate, tail-flick, and formalin tests in rodents. Curr Protoc Neurosci 2007; Chapter 8: Unit 8.9.
14. Foroud M, Vesal N. Evaluation of the anti-nociceptive effects of morphine, tramadol, meloxicam and their combinations using the tail-flick test in rats. Vet Res Forum 2015; 6(4): 313-318.
15. Directive 2010/63/EU of the European Parliament and of the Council of 22 September 2010 on the protection of animals used for scientific purposes.
16. Lee KH, Lee DW, Kang BC. The ‘R’ principles in laboratory animal experiments. Lab Anim Res 2020; 36: 45.
17. Karrat L, Abajy MY, Nayal R. Investigating the anti-inflammatory and analgesic properties of leaves ethanolic extracts of Cedruslibani and Pinus brutia. Heliyon 2022; 8(4): e09254.
18. Azim T, Wasim M, Akhtar MS, et al. An in vivo evaluation of anti-inflammatory, analgesic and anti-pyretic activities of newly synthesized 1,2,4 Triazole derivatives. BMC Complement Med Ther 2021; 21: 304.
19. Alfaro RA, Davis DD. Diclofenac. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan.
20. Krishna Sailaja A, Nandini M, Preparation of diclofenac nanoparticles by desolvat ion technique using acetone as desolvating agent. IJNDD 2016; 8(1): 42-45.
21. Khanal S, Adhikari U, Rijal NP et al. pH-responsive PLGA nanoparticle for controlled payload delivery of diclofenac sodium. J Funct Biomater 2016; 7: 21.
22. Duarte Junior AP, Tavares EJM, Alves TVG et al. Chitosan nanoparticles as a modified diclofenac drug release system. J Nanopart Res 2017; 19: 274.
23. Cooper DL, Harirforoosh S. Design and optimization of PLGA-based diclofenac loaded nanoparticles. PLOS ONE 2014; 9(1): e87326.
24. Cao Y, Dong X, Chen X. Polymer-modified liposomes for drug delivery: from fundamentals to applications. Pharmaceutics 2022; 14(4): 778.
25. Robson AL, Dastoor PC, Flynn J, et al. Advantages and limitations of current imaging techniques for characterizing liposome morphology. Front Pharmacol 2018; 9: 80.
26. Aguilar-Pérez K, Avilés-Castrillo J, Medina DI, et al. Insight into nanoliposomes as smart nanocarriers for greening the twenty-first century biomedical settings. Front Bioeng Biotechnol 2020; 8: 1441.
27. Alqahtani F, Aleanizy F, El Tahir E, et al. Antibacterial activity of chitosan nanoparticles against pathogenic N. gonorrhoea. Int J Nanomed 2020; 13; 15: 7877-7887.
28. Rasel MAT, Hasan M. Formulation and evaluation of floating alginate beads of diclofenac sodium. Dhaka University J Pharm Sci 2012; 11: 29-35.
29. Fan L, Lu Y, Yang LY. Fabrication of polyethylenimine-functionalized sodium alginate/ cellulose nanocrystal/polyvinyl alcohol core-shell microspheres ((PVA/SA/CNC)@PEI) for diclofenac sodium adsorption. J Colloid Interface Sci 2019; 554: 48-58.
30. Ajith K, Hyma P, Tumma A. Liposome’s: microscopic vesicles formulated using diclofenac sodium. J Global Trends Pharm Sci 2017; 5(2): 1668-1671.
31. Sabeti B, Noordine MIB, Javar HA, et al. Characterization of diclofenac liposomes formulated with palm oil fractions. BioMed Res Int 2014; 2014: ID 765426.
32. Rajendar M, Srinivas A Preparation, optimization and evaluation of liposomes encapsulating diclofenac sodium and charge inducers to enhance stability using lipid hydration method. Int J Pharm Pharmaceut Res 2016; 5(1): 41-48.

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