Herbal nano-ointment containing encapsulated polysaccharide in repairing of superficial ulcers

Document Type : Research Paper

Authors

1 Department of Biology, Faculty of Science, Razi University, Kermanshah, Iran

2 Nano Drug Delivery Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran

3 Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran

4 School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran

Abstract

Objective(s): Skin wounds are appraised as a rapidly growing threat to the economy and public health. Wound management is the main goal to promote rapid repair, with functional and esthetic outcomes. Among several wound healers, ointments are the most cost-effective and highly functional.  
Materials and Methods: Here, polysaccharide was isolated from Rosa canina and structural analysis was performed by NMR, LC-MS/MS, and FTIR. Then, the polysaccharide was encapsulated in SLN through the dialysis process. Structural analysis was committed to a survey on the physical and chemical properties of polysaccharide-SLN (PS-SLN) complex by Uv-Vis spectrophotometry, dynamic light scattering (DLS), and scanning electron microscopy (SEM) technologies. The ointment was prepared by adding PS-SLN to R. canina oil and beeswax.  
Results: The prepared PS-SLN nanoparticles had monodispersity with a size of about 217 nanometers.  The nano-ointment showed high stability with a pH of about 6 and a high density near 3256 centipoises. The skin absorption of the compounds was determined by the Franz cells. The in vitro skin absorption indicated that during the first 12 hr 36% of our nano-ointment’s skin permeation and then continued up to 12 hr to 51%. The higher healing rate of nano-ointment than positive control with no allergic effects confirmed its efficiency in wound management.  
Conclusion: The results indicated that the nano-ointment could be applied for the healing of scars in pre-clinical and clinical trials. Owing to effectual scar healing, nano-ointment may be effective in the treatment of other wounds including burn, diabetic and chronic ones. 

Keywords


1.  Benirschke SK, Kramer PA. Wound healing complications in closed and open calcaneal fractures. J Orthop Trauma. 2004;18(1):1-6. 
2. Sen CK. Human Wound and Its Burden: Updated 2020 Compendium of Estimates. Adv Wound Care (New Rochelle). 2021;10(5):281-292.
3. Nussbaum SR, Carter MJ, Fife CE, DaVanzo J, Haught R, Nusgart M, Cartwright D. An Economic Evaluation of the Impact, Cost, and Medicare Policy Implications of Chronic Nonhealing Wounds. Value Health. 2018;21(1):27-32.
4. Guest JF, Fuller GW, Vowden P. Cohort study evaluating the burden of wounds to the UK’s National Health Service in 2017/2018: update from 2012/2013. BMJ Open. 2020 22;10(12):e045253.
5. Ennis W. Assessing the impact of coronavirus on wound care patients and practice. 2020.
6. Yang SW, Geng ZJ, Ma K, Sun XY, Fu XB. Comparison of the histological morphology between normal skin and scar tissue. J Huazhong Univ Sci Technolog Med Sci. 2016;36(2):265-269.
7. Profyris C, Tziotzios C, Do Vale I. Cutaneous scarring: Pathophysiology, molecular mechanisms, and scar reduction therapeutics Part I. The molecular basis of scar formation. J Am Acad Dermatol. 2012;66(1):1-10.
8. Chouhan D, Dey N, Bhardwaj N, Mandal BB. Emerging and innovative approaches for wound healing and skin regeneration: Current status and advances. Biomaterials. 2019;216:119267. 
9. Maver T, Maver U, Stana Kleinschek K, Smrke DM, Kreft S. A review of herbal medicines in wound healing. Int J Dermatol. 2015;54(7):740-751. 
10. Das U, Behera SS, Pramanik K. Ethno-Herbal-Medico in Wound Repair: An Incisive Review. Phytother Res. 2017;31(4):579-590. 
11. Shedoeva A, Leavesley D, Upton Z, Fan C. Wound healing and the use of medicinal plants. J Evid Based Integr Med. 2019;2019:2684108.
12. Ahmed J, Gultekinoglu M, Edirisinghe M. Bacterial cellulose micro-nano fibres for wound healing applications. Biotechnol Adv. 2020;41:107549.
13.    Jafari H, Bernaerts KV, Dodi G, Shavandi A. Chitooligosaccharides for wound healing biomaterials engineering. Mater Sci Eng C Mater Biol Appl. 2020;117:111266.
14.    Naseri-Nosar M, Ziora ZM. Wound dressings from naturally-occurring polymers: A review on homopolysaccharide-based composites. Carbohydr Polym. 2018 Jun 1;189:379-398. 
15.    Bremecker KD, Strempel H, Klein G. Novel concept for a mucosal adhesive ointment. J Pharm Sci. 1984 Apr;73(4):548-552. 
16.    Firooz A, Namdar R, Nafisi S, Maibach HI. Nano-Sized Technologies for Miconazole Skin Delivery. Curr Pharm Biotechnol. 2016;17(6):524-531.
17.    Rahimi M, Sajadimajd S, Mahdian Z, Hemmati M, Malekkhatabi P, Bahrami G, Mohammadi B, Miraghaee S, Hatami R, Mansouri K, Moahammadi Motlagh HR, Keshavarzi S, Derakhshankhah H. Characterization and anti-diabetic effects of the oligosaccharide fraction isolated from Rosa canina in STZ-Induced diabetic rats. Carbohydr Res. 2020;489:107927. 
18.    Motiei M, Kashanian S. Novel amphiphilic chitosan nanocarriers for sustained oral delivery of hydrophobic drugs. Eur J Pharm Sci. 2017;99:285-291. 
19.    Herndl GJ, Kaltenböck E, Müller-Niklas G. Dialysis bag incubation as a nonradiolabeling technique to estimate bacterioplankton production in situ. InHandbook of methods in aquatic microbial ecology 2018; 553-556. 20.Koliyote S, Misal B. Evaluation of anti-inflammatory activity of topical gel by carrageenan induced paw oedema method. Int J Pharm Stud Res. 2013;2:579-584.
21.    Nour S, Shalaby S, Afify N, AbdeI Aal S, Kamal M. Formulationand evaluation of econazole nitrate emulgels. J Drug Res. 2002;24(1-2):63-71.
22.    Huh Y, Lee DH, Choi D, Lim KM. Effect of cosmetics use on the in vitro skin absorption of a biocide, 1, 2-Benzisothiazolin-3-one. Toxics. 2022;10(3):108.
23.    Draize JH. Methods for the study of irritation and toxicity of substances applied topically to the skin and the mucous membranes. J Pharmacol Exp Ther. 1944;82:377-390.
24.  Yadav E, Yadav P, Verma A. Amelioration of full thickness dermal wounds by topical application of biofabricated zinc oxide and iron oxide nano-ointment in albino Wistar rats. J Drug Deliv Sci Technol. 2021 ;66:102833.
25. Kubendiran L, Theerthagiri S, Al-Dhabi NA, Palaninaicker S, Subramanian SM, Srinivasan V, Karuppiah P. In vitro preparation of biosurfactant based herbal-nano topical ointment from Tridax procumbens infused oil using gelatin stabilized silver nanoparticle and its efficacy on fibroblastic cell lines. Appl Nanosci. 2023;13(1):719-734.
26. Kaliamurthi S, Selvaraj G, Thirugnanasambandam R, Thangavel B. Topical delivery of nano-encapsulated rutoside medication for diabetic foot ulcer in rat model. Nanoscience & Nanotechnology-Asia. 2018;8(1):116-129. 
27. Fattahi A, Niyazi F, Shahbazi B, Farzaei MH, Bahrami G. Antidiabetic mechanisms of Rosa canina fruits: an in vitro evaluation. J Evid Based Integr Med. 2017;22(1):127-133.
28. Bahrami G, Naseri R, Khosravifar M, Sajadimajd S, Mohammadi B, Heydarpour F, Cheraghialiakbari S. The Safety and Effectiveness of a Polysaccharide Extracted from Rosa Canina in Patients with NAFLD: A Randomized Trial. Clin Diabetol. 2022;11(4):239-244.
29. Samadian H, Zamiri S, Ehterami A, Farzamfar S, Vaez A, Khastar H, Alam M, Ai A, Derakhshankhah H, Allahyari Z, Goodarzi A. Electrospun cellulose acetate/gelatin nanofibrous wound dressing containing berberine for diabetic foot ulcer healing: In vitro and in vivo studies. Sci Rep. 2020 20;10(1):8312.
30. Sartika D, Syamsu K, Warsiki E, Fahma F, Arnata IW. Nanocrystalline cellulose from kapok fiber (Ceiba pentandra) and its reinforcement effect on alginate hydrogel bead. Starke. 2021;73(9-10):2100033.
31.    Chang C, Duan B, Cai J, Zhang L. Superabsorbent hydrogels based on cellulose for smart swelling and controllable delivery. Eur Polym J. 2010;46(1):92-100.
32.    Hu D, Zeng M, Sun Y, Yuan J, Wei Y. Cellulose‐based hydrogels regulated by supramolecular chemistry. SusMat. 2021;1(2):266-284.
33.    Asanarong O, Quan VM, Boonrungsiman S, Sukyai P. Bioactive wound dressing using bacterial cellulose loaded with papain composite: Morphology, loading/release and antibacterial properties. Eur Polym J. 2021;143:110224.
34.    Singla R, Soni S, Patial V, Kulurkar PM, Kumari A, Padwad YS, Yadav SK. Cytocompatible anti-microbial dressings of s yzygium cumini cellulose nanocrystals decorated with silver nanoparticles accelerate acute and diabetic wound healing. Sci Rep. 2017;7(1):10457.
35.    Huang W, Wang Y, Huang Z, Wang X, Chen L, Zhang Y, Zhang L. On-demand dissolvable self-healing hydrogel based on carboxymethyl chitosan and cellulose nanocrystal for deep partial thickness burn wound healing. ACS Appl Mater Interfaces. 2018;10(48):41076-41088.
36.    Vijayan V, Rao DS, Jayachandran E, Anburaj J. Preparation and characterization of anti-diabetic drug-loaded solid lipid nanoparticles. JITPS. 2010;1(8):320-328.
37.    Ala A, Ebrahimi Bakhtavar H, Shams Vahdati S, Rahmani F, Azargoun M, Ebrahimi Bakhtavar H. Effects of Silver Sulfadiazine and Adibderm® Herbal Ointments in Treatment of Patients with Second Degree Burns: A Randomized Clinical Trial. Trauma Mon. 2018;23(2):1-7.
38.    Pool H, Quintanar D, de Dios Figueroa J, Mano CM, Bechara JE, Godínez LA, Mendoza S. Antioxidant effects of quercetin and catechin encapsulated into PLGA nanoparticles. J nanomater. 2012;2012:86.
39.    Gürbüz I, Ustün O, Yesilada E, Sezik E, Kutsal O. Anti-ulcerogenic activity of some plants used as folk remedy in Turkey. J Ethnopharmacol. 2003;88(1):93-97. 
40.    Valerón-Almazán P, Gómez-Duaso AJ, Santana-Molina N, García-Bello MA, Carretero G. Evolution of post-surgical scars treated with pure rosehip seed oil. Journal of Cosmetics, Dermatol Sci Appl. 2015;5(02):161.
41.    Johnson W, Bergfeld WF, Belsito DV, Hill RA, Klaassen CD, Liebler DC, Marks JG, Shank RC, Slaga TJ, Snyder PW, Gill LJ, Heldreth B. Safety Assessment of Rosa canina-derived Ingredients as Used in Cosmetics. Int J Toxicol. 2022; 41(1_suppl):44S-60S.
42.    Zhao B, Zhang X, Han W, Cheng J, Qin Y. Wound healing effect of an Astragalus membranaceus polysaccharide and its mechanism. Mol Med Rep. 2017;15(6):4077-4083. 
43.    Trombetta D, Puglia C, Perri D, Licata A, Pergolizzi S, Lauriano ER, De Pasquale A, Saija A, Bonina FP. Effect of polysaccharides from Opuntia ficus-indica (L.) cladodes on the healing of dermal wounds in the rat. Phytomedicine. 2006;13(5):352-358.