Original Article

Evaluation of Nanonanoliposomal Curcumin on Cutaneous Leishmaniasis Skin Lesions Caused by Leishmania major in BALB/c Mice

Abstract

Background: Curcumin is an extract of rhizome turmeric (diferuloylmethane), with antioxidant, anti-inflammatory, antimicrobial, and anti-parasitic properties, which making it a potential candidate for the treatment of leishmaniasis. The aim of the presented study was to evaluate curcumin as possible candidate for treatment of cutaneous leishmaniasis. 
Methods: We investigated the physicochemical properties and anti-leishmanial effects of nanoliposomal curcumin (40, 80, and 120 μM) in Leishmania major (MRHO/IR/75/ER) infected BALB/c mice at the faculty of Veterinary Medicinem University of Tehran, Iran. For this aim, L. major promastigotes (MHROM/IR/75/ER) at stationary phase (2×106) were inoculated sub-cutaneously into the upper area of the tail in BALB/c mice (six groups, n= 10 per group). For evaluation of nanoliposomal curcumin, the zeta potential, particle size and stability of nanoliposomal curcumin was determined. Furthermore, the anti-leishmanial effects of nanoliposomal curcumin formulation on the lesion sizes was determined and the parasite burden in the leishmania induced lesion was performed using semi quantitative PCR.
Results: Treatment of L. major infected BALB/c mice with nanoliposomal curcumin led to a reduction in the kinetic of the skin lesion size development. The semi quantitative PCR analysis of DNA extracted from the lesions showed reduction of parasite burden. The most effective treatment could be found in 80 μM nanoliposomal curcumin. Treatment with Glucantime, as a positive control, also showed a nearly similar effect compared to the effect of 80 μM nanoliposomal curcumin.
Conclusion: Nanoliposomal curcumin could be considered as a potential drug against cutaneous leishmaniasis caused by L. major in susceptible animal models.

1. Torres-Guerrero E, Quintanilla-Cedillo MR, Ruiz-Esmenjaud J, et al. Leishmaniasis: a review. F1000Res. 2017;6:750.
2. Mann S, Frasca K, Scherrer S, et al. A review of leishmaniasis: current knowledge and future directions. Curr Trop Med Rep. 2021;8(2):121-32.
3. Gradoni L. A brief introduction to leishmaniasis epidemiology. The Leishmaniases: Old Neglected Tropical Diseases. 2018: 1-13.
4. Gillespie PM, Beaumier CM, Strych U, et al. Status of vaccine research and development of vaccines for leishmaniasis. Vaccine. 2016;34(26):2992-2995.
5. Firooz A, Mortazavi H, Khamesipour A, et al. Old world cutaneous leishmaniasis in Iran: clinical variants and treatments. J Dermatolog Treat. 2021; 32(7):673-683.
6. Hadighi R, Mohebali M, Boucher P, et al. Unresponsiveness to Glucantime treatment in Iranian cutaneous leishmaniasis due to drug-resistant Leishmania tropica parasites. PLoS Med. 2006; 3(5):e162.
7. Lyra MR, Passos SR, Pimentel MI, et al. Pancreatic toxicity as an adverse effect induced by meglumine antimoniate therapy in a clinical trial for cutaneous leishmaniasis. Rev Inst Med Trop Sao Paulo. 2016;58:68.
8. Shakibaei M, Mobasheri A, Lueders C, Busch F, Shayan P, Goel A. Curcumin enhances the effect of chemotherapy against colorectal cancer cells by inhibition of NF-κB and Src protein kinase signaling pathways. PLoS One. 2013;8(2):e57218.
9. Shakibaei M, Buhrmann C, Kraehe P, Shayan P, Lueders C, Goel A. Curcumin chemosensitizes 5-fluorouracil resistant MMR-deficient human colon cancer cells in high density cultures. PLoS One. 2014;9(1):e85397.
10. Buhrmann C, Kraehe P, Lueders C, et al. Curcumin suppresses crosstalk between colon cancer stem cells and stromal fibroblasts in the tumor microenvironment: potential role of EMT. PLoS One. 2014;9(9):e107514.
11. Buhrmann C, Shayan P, Banik K, et al. Targeting NF-κB signaling by calebin a, a compound of turmeric, in multicellular tumor microenvironment: Potential role of apoptosis induction in CRC cells.. Biomedicines. 2020;8(8):236.
12. Sasaki J, Kichida M. Curcumin: biosynthesis, medicinal uses and Health benefits. Nova Science Publishers, Incorporated; 2012.
13. Zhang L, Luo J, Zhang M, et al. Effects of curcumin on chronic, unpredictable, mild, stress-induced depressive-like behaviour and structural plasticity in the lateral amygdala of rats. Int J Neuropsychopharmacol. 2014;17(5):793-806.
14. Aqeele G, Shayan P, Abkooh EE, et al. Evaluation of curcumin and CM11 peptide alone and in combination against amastigote form of Iranian strain of L. major (MRHO/IR75/ER) in vitro. Exp Parasitol. 2021;229:108151.
15. Aqeele G, Shayan P, Ebrahimzadeh E, et al. Determination of the Effective Dose of Curcumin alone and in Combination with Antimicrobial Peptide CM11 on Promastigote Forms of Iranian Strain of L. major (MRHO/IR/75/ER). Arch Razi Inst. 2019;74(4):413-422.
16. Saberi R, Fakhar M, Asfaram S, et al. A systematic literature review of curcumin with promising antileishmanial activity. Infect Disord Drug Targets. 2021;21(3):363-369.
17. de Vries HJ, Reedijk SH, Schallig HD. Cutaneous leishmaniasis: recent developments in diagnosis and management. Am J Clin Dermatol. 2015;16(2):99-109.
18. Roatt BM, de Oliveira Cardoso JM, De Brito RC, et al. Recent advances and new strategies on leishmaniasis treatment. Appl Microbiol Biotechnol. 2020;104(21):8965-8977.
19. Iranpour S, Hosseinzadeh A, Alipour A. Efficacy of miltefosine compared with glucantime for the treatment of cutaneous leishmaniasis: a systematic review and meta-analysis. Epidemiol Health. 2019; 41:e2019011.
20. Sundar S, Chakravarty J, Meena LP. Leishmaniasis: treatment, drug resistance and emerging therapies. Expert Opinion on Orphan Drugs. 2018;7(1):1-10.
21. Kumar A. Leishmania and leishmaniasis. In: Briefs in Immunology (BRIEFSIMMUN, volume 3) 2013. Springer Publication.
22. El-Sheridy NA, El-Moslemany RM, Ramadan AA, et al. Enhancing the in vitro and in vivo activity of itraconazole against breast cancer using miltefosine-modified lipid nanocapsules. Drug Deliv. 2021;28(1):906-919.
23. Dorlo TP, Balasegaram M, Beijnen JH, et al. Miltefosine: a review of its pharmacology and therapeutic efficacy in the treatment of leishmaniasis. J Antimicrob Chemother. 2012;67(11):2576-2597.
24. Adler-Moore J, Proffitt RT. Effect of tissue penetration on AmBisome efficacy. Curr Opin Investig Drugs. 2003;4(2):179-185.
25. Laniado-Laborín R, Cabrales-Vargas MN. Amphotericin B: side effects and toxicity. Rev Iberoam Micol. 2009;26(4):223-227.
26. Saberi R, Zadeh AG, Afshar MJ, Fakhar M, Keighobadi M, Mohtasebi S, Rahimi-Esboei B. In vivo anti-leishmanial activity of concocted herbal topical preparation against Leishmania major (MRHO/IR/75/ER). Ann Parasitol. 2021;67(3):483-488.
27. Parvizi MM, Zare F, Handjani F, et al. Overview of herbal and traditional remedies in the treatment of cutaneous leishmaniasis based on Traditional Persian Medicine. Dermatol Ther. 2020;33(4):e13566.
28. Hamdan S, Pastar I, Drakulich S, et al. Nanotechnology-driven therapeutic interventions in wound healing: potential uses and applications. ACS Cent Sci. 2017;3(3):163-175.
29. Jacob J, Haponiuk JT, Thomas S, et al. Biopolymer based nanomaterials in drug delivery systems: A review. Materials Today. 2018;9:43-55.
30. Fattahi Bafghi A, Haghirosadat BF, Yazdian F, Mirzaei F, Pourmadadi M, Pournasir F, Hemati M, Pournasir S. A novel delivery of curcumin by the efficient nanoliposomal approach against Leishmania major. Prep Biochem Biotechnol. 2021;51(10):990-997.
31. Najafian HR, Mohebali M, Rezayat SM, et al. Nanoliposomal miltefosine for the treatment of cutaneous leishmaniasis caused by Leishmania major (MRHO/IR/75/ER): The drug preparation and in vitro study. Int J Pharm Res Allied Sci. 2016; 5(3):97-107
32. Akbari M, Askari ZA, Sadri K, et al. Antileishmanial activity of nanoliposomes containing curcumin in vitro and in vivo. Journal of Dermatology and Cosmetic. 2018;8(4):204-217.
Files
IssueVol 19 No 2 (2024) QRcode
SectionOriginal Article(s)
DOI https://doi.org/10.18502/ijpa.v19i2.15859
Keywords
Nanoliposomal curcumin Cutaneous leishmaniasis Leishmania major BALB/c mice Semi quantitative PCR
Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
1.
Shirmohammad S, Mohebali M, Arabkhazaeli F, Hassan J, Shayan D, Amininia N, Shayan P. Evaluation of Nanonanoliposomal Curcumin on Cutaneous Leishmaniasis Skin Lesions Caused by Leishmania major in BALB/c Mice. Iran J Parasitol. 2024;19(2):238-246.