The effect of topical quercetin loaded liposome on pressure ulcer healing in rats

Document Type : Research Paper

Authors

1 Nanotechnology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

2 Department of Pharmaceutics, Faculty of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

3 Department of Pharmacology, Faculty of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

4 Student Research Committee, Faculty of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

5 Department of Pathobiology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran

Abstract

Objective(s): Quercetin antioxidant properties could play an important role in various fields of health. However, its use has been limited because of several disadvantages such as very low solubility in water and high instability in the presence of air, light and heat. Encapsulation of quercetin in nanostructure systems such as liposome may lead to decrease the adverse effects and protect this molecule against degradation. The aim of this study was preparation and in-vitro and in-vivo evaluation of liposomes for topical delivery of quercetin to improve the pressure ulcers.
Materials and Methods: Liposomal formulations were prepared by fusion method and characterized. The amount of drug retained in and penetrated through mouse skin after 8 hours were determined. Also microscopic and macroscopic examination of laboratory animals was performed.
Results:  Encapsulation efficacy of liposomes was in range 64.66-77.83%. Formulation F4 showed maximum drug release in 8 hours and the remaining drug in the skin layers was more than 46%. Histological investigation suggested that F4 and phenytoin 1% cream have the healing effect on the pressure ulcer during 28 day-treatment.
Conclusion: Quercetin liposomes due to its natural structure and minimal systemic absorption and side effects can be a suitable candidate for the treatment of pressure ulcers.

Keywords

References

1. Bosisio E, Benelli C, Pirola O. Effect of the flavanolignans of silybum marianum l. On lipid peroxidation in rat liver microsomes and freshly isolated hepatocytes. Pharmacol Res. 1992; 25: 147-165.
2. Verma AK, Johnson JA, Gould MN, Tanner MA. Inhibition of 7, 12-dimethylbenz (a) anthracene-and n-nitrosomethylurea-induced rat mammary cancer by dietary flavonol quercetin. Cancer Res. 1988; 48: 5754-5758.
3. Pralhad T, Rajendrakumar K. Study of freeze-dried quercetin–cyclodextrin binary systems by dsc, ft-ir, x-ray diffraction and sem analysis. J Pharm Biomed Anal. 2004; 34: 333-339
4. Areias FM, Rego AC, Oliveira CR, Seabra RM. Antioxidant effect of flavonoids after ascorbate/fe2+-induced oxidative stress in cultured retinal cells1. Biochem Pharmacol. 2001; 62: 111-118
5. Oteiza PI, Erlejman AG, Verstraeten SV, Keen CL, Fraga CG. Flavonoid-membrane interactions: A protective role of flavonoids at the membrane surface? Clinical Development Immunology. 2005; 12: 19-25.
6. Kant V, Jangir BL, Kumar V, Nigam A, Sharma V. Quercetin accelerated cutaneous wound healing in rats by modulation of different cytokines and growth factors. Growth Factors. 2020; 38: 105-119.
7. Yin G, Wang Z, Wang Z, Wang X. Topical application of quercetin improves wound healing in pressure ulcer lesions. Exp Dermatol. 2018; 27: 779-786.
8. Guo C, Yang RJ, Jang K, Zhou X, Liu Y. Protective effects of pretreatment with quercetin against lipopolysaccharide-induced apoptosis and the inhibition of osteoblast differentiation via the mapk and wnt/β-catenin pathways in mc3t3-e1 cells. Cell Physiol Biochem. 2017; 43: 1547-1561.
9. Cho SY, Park SJ, Kwon MJ, Jeong TS, Bok SH, Choi WY, et al. Quercetin suppresses proinflammatory cytokines production through map kinases andnf-kappab pathway in lipopolysaccharide-stimulated macrophage. Mol Cell Biochem. 2003; 243: 153-160.
10. Kanitakis J. Anatomy, histology and immunohistochemistry of normal human skin. Eur J Dermatol. 2002; 12: 390-399
11. Nair KS, Taly A, Roopa N, Murali T. Pressure ulcers: An unusual complication of indwelling urethral catheter. Spinal Cord. 2001; 39: 234.
12. Peirce SM, Skalak TC, Rodeheaver GT. Ischemia‐reperfusion injury in chronic pressure ulcer formation: A skin model in the rat. Wound Repair Regen. 2000; 8: 68-76.
13. Smith MB, Totten A, Hickam DH, Fu R, Wasson N, Rahman B, et al. Pressure ulcer treatment strategies: A systematic comparative effectiveness review. Ann Intern Med. 2013; 159: 39-50.
14. Bergstrom N, Allman RM, Alvarez OM, Bennett MA, Marvel EM, Reger SI, et al. Pressure ulcer treatment: Quick reference guide for clinicians. Plast Surg Nurs. 1995; 15: 1-50.
15. Lyder CH. Pressure ulcer prevention and management. JAMA. 2003; 289: 223-226.
16. Alizadeh AM, Sohanaki H, Khaniki M, Mohaghgheghi MA, Ghmami G, Mosavi M. The effect of teucrium polium honey on the wound healing and tensile strength in rat. Iran J Basic Med Sci. 2011; 14: 499.
17. Shaji J, Iyer S, Preparation. optimization and in-vivo hepatoprotective evaluation of quercetin liposomes. Int J Current Pharml Res. 2012; 4: 24-32.
18. Neha VM, Namita TM, Srendran CS, Viral SH. Formulation optimization and evaluation of liposomal gel of prednisolone by applying statistical design. Indian J Res Pharm Biotech. 2013; 1: 180.
19. Pierre MBR, Costa IdSM. Liposomal systems as drug delivery vehicles for dermal and transdermal applications. Arch Dermatol Res. 2011; 303: 607.
20. Bavarsad N, Hemmati G, Ataee S, Sistani Karampour N. Preparation and physicochemical characterization of topical quercetin loaded liposome. Ars Pharm. 2019; 60: 41-46.
21. Zsila F, Bikádi Z, Simonyi M. Probing the binding of the flavonoid, quercetin to human serum albumin by circular dichroism, electronic absorption spectroscopy and molecular modelling methods. Biochem Pharmacol. 2003; 65: 447-456.
22. Raza K, Singh B, Lohan S, Sharma G, Negi P, Yachha Y, et al. Nano-lipoidal carriers of tretinoin with enhanced percutaneous absorption, photostability, biocompatibility and anti-psoriatic activity. Int J Pharm. 2013; 456: 65-72.
23.  Jafari B, Rafie F, Davaran S. Preparation and characterization of a novel smart polymeric hydrogel for drug delivery of insulin. BioImpacts: BI. 2011; 1: 135.
24. Khan GM, Frum Y, Sarheed O, Eccleston GM, Meidan VM. Assessment of drug permeability distributions in two different model skins. Int J Pharm. 2005; 303: 81-87.
25. Panwar P, Pandey B, Lakhera P, Singh K. Preparation, characterization, and in vitro release study of albendazole-encapsulated nanosize liposomes. Int J Nanomed. 2010; 5: 101.
26. Jaafari MR, Bavarsad N, Bazzaz BSF, Samiei A, Soroush D, Ghorbani S, et al. Effect of topical liposomes containing paromomycin sulfate in the course of leishmania major infection in susceptible balb/c mice. Antimicrob Agents Chemother. 2009; 53: 2259-2265.
27. Biswas TK, Pandit S, Chakrabarti S, Banerjee S, Poyra N, Seal T. Evaluation of cynodon dactylon for wound healing activity. J Ethnopharmacol. 2017; 197: 128-137.
28. Lee J-J, Yu H-S, Hong S-J, Jeong I, Jang J-H, Kim H-W. Nanofibrous membrane of collagen–polycaprolactone for cell growth and tissue regeneration. J Mater Sci Mater Med. 2009; 20: 1927-1935.
29. Kopecki Z, Luchetti M, Adams D, Strudwick X, Mantamadiotis T, Stoppacciaro A, et al. Collagen loss and impaired wound healing is associated with c‐myb deficiency. J Pathol. 2007; 211: 351-361.
30. Chen-yu G, Chun-fen Y, Qi-lu L, Qi T, Yan-wei X, Wei-na L, et al. Development of a quercetin-loaded nanostructured lipid carrier formulation for topical delivery. Int J Pharm. 2012; 430: 292-298.
31. Elmeshad A, Mortazavi S, Mozafari M. Formulation and characterization of nanoliposomal 5-fluorouracil for cancer nanotherapy. J Liposome Res. 2014; 24: 1-9.
32. Zidan AS, Spinks C, Fortunak J, Habib M, Khan MA. Near-infrared investigations of novel anti-hiv tenofovir liposomes. The AAPS Journal. 2010; 12: 202-214.
33. Jangde R, Singh D. Preparation and optimization of quercetin-loaded liposomes for wound healing, using response surface methodology. Artif Cells Nanomed Biotechnol. 2016; 44: 635-641.
34. Bavarsad N, Bazzaz BSF, Khamesipour A, Jaafari MR. Colloidal, in vitro and in vivo anti-leishmanial properties of transfersomes containing paromomycin sulfate in susceptible balb/c mice. Acta Trop. 2012; 124: 33-41.
35. Castangia I, Nácher A, Caddeo C, Valenti D, Fadda AM, Díez-Sales O, et al. Fabrication of quercetin and curcumin bionanovesicles for the prevention and rapid regeneration of full-thickness skin defects on mice. Acta Biomater. 2014; 10: 1292-1300.
36. Liu D, Hu H, Lin Z, Chen D, Zhu Y, Hou S, et al. Quercetin deformable liposome: Preparation and efficacy against ultraviolet b induced skin damages in vitro and in vivo. J Photochem Photobiol B: Biol. 2013; 127: 8-17.
37. Kataria S, Sandhu P, Bilandi A, Akanksha M, Kapoor B. Stealth liposomes: A review. Int J Res Ayurveda Pharm. 2011; 2: 1534-1538.
38. Ferreira LS, Ramaldes GA, Nunan EA, Ferreira LA. In vitro skin permeation and retention of paromomycin from liposomes for topical treatment of the cutaneous leishmaniasis. Drug Dev Ind Pharm. 2004; 30: 289-296.
39. Fetih G, Fathalla D, El‐Badry M. Liposomal gels for site‐specific, sustained delivery of celecoxib: In vitro and in vivo evaluation. Drug Dev Res. 2014; 75: 257-266.
40. El Goweini M, El Din N. Effect of quercetin on excessive dermal scarring. Egyptian Dermatol Online J. 2005; 1: 1-10
41. Abedian Z, Navinezhad M, Asili J, Esmaeili H. An investigation into the effect of alpha ointment (fundermol) on perineal pain relief following episiotomy in nulliparous women. J Midwif Reproduct Health. 2018; 6: 1149-1156
42. Ashcroft GS, Dodsworth J, Van Boxtel E, Tarnuzzer RW, Horan MA, Schultz GS, et al. Estrogen accelerates cutaneous wound healing associated with an increase in tgf-β1 levels. Nat Med. 1997; 3: 1209.
43. Kondo T, Ishida Y. Molecular pathology of wound healing. Forensic Sci Int. 2010; 203: 93-98.
44. Kyriakides TR, Tam JW, Bornstein P. Accelerated wound healing in mice with a disruption of the thrombospondin 2 gene. J Invest Dermatol. 1999; 113: 782-787.
Nanomedicine Journal
Volume 8, Issue 3
July 2021
Pages 187-199

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