Safety Evaluation of Nano-Liposomal Formulation of Amphotericin B (SinaAmpholeish) in Animal Model as a Candidate for Treatment of Cutaneous Leishmaniasis

  • Seyed Ebrahim Eskandari Center for Research and Training in Skin Diseases and Leprosy (CRTSDL), Tehran University of Medical Sciences, Tehran, Iran
  • Alireza Firooz Center for Research and Training in Skin Diseases and Leprosy (CRTSDL), Tehran University of Medical Sciences, Tehran, Iran
  • Mansour Nassiri-Kashani Center for Research and Training in Skin Diseases and Leprosy (CRTSDL), Tehran University of Medical Sciences, Tehran, Iran
  • Mahmoud Reza Jaafari Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran . Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
  • Amir Javadi Center for Research and Training in Skin Diseases and Leprosy (CRTSDL), Tehran University of Medical Sciences, Tehran, Iran . School of Allied Sciences, Tehran University of Medical Sciences, Tehran, Iran
  • Akram Miramin-Mohammadi Center for Research and Training in Skin Diseases and Leprosy (CRTSDL), Tehran University of Medical Sciences, Tehran, Iran
  • Hossein Valian-Keshavarz Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran . Center for Research of Endemic Parasites of Iran, Tehran University of Medical Sciences, Tehran, Iran
  • Ali Khamesipour Center for Research and Training in Skin Diseases and Leprosy (CRTSDL), Tehran University of Medical Sciences, Tehran, Iran
Keywords: Cutaneous leishmaniasis, Nano-liposomes, Amphotericin B, Draize test

Abstract

Background: Development of a topical treatment for cutaneous leishmaniasis (CL) is an important step in the im­provement of lesion management. Amphotericin B (AmB) is effective against Leishmania species but it is toxic, a Nano-liposomal form of AmB with a size of about 100nm (Lip-AmB) was developed and showed to be effective against Leishmania major, and Leishmania tropica in vitro and against L. major in vivo in animal model. This study was designed to check the irritancy Draize test in rabbits and was completed in the Center for Research and Training in Skin Diseases and Leprosy, TUMS, in 2012.Methods: Twenty rabbits in 3 steps were housed individually with artificial lighting (12/12h light/dark). SinaAm­pholeish cream or empty liposomes (prepared under GMP condition at Minoo Company, Tehran, Iran), was applied on a gauze patch and the patches were placed on the designated sites of the skin in the back of the rabbits. At 48 and 72h later, the erythema and oedema were checked, scored and recorded.Results: The erythema score in rabbits was 0.83+0.41 for the SinaAmpholeish and 0.5+0.55 for empty liposomes (P= 0.16). The average score for oedema was 0.67+0.52 for SinaAmpholeish and 0.33+0.52 for empty liposomes (P= 0.16).Conclusion: Based on skin irritancy reactions the topical formulation of SinaAmpholeish is safe and could be further checked in human trials.

References

WHO (2016) Leishmaniasis fact sheet no. 375. World Health Organization, Ge-neva, Switzerland. http://www.who.int/mediacentre/factsheets/fs375/en/

WHO Report on Global Surveillance of Ep¬idemic-prone Infectious Diseases Leish¬maniasis. http://www.who.int/csr/resources/publications/CSR_ISR_2000_1leish/en/

Alvar J, Vélez ID, Bern C, Herrero M, Desjeux P, Cano J, Jean Jannin, Margriet den Boer (2012) Leishmania¬sis worldwide and global estimates of its inci¬dence. PLoS One. 7(5): 1–12.

Firooz A, Khamesipour A, Ghoorchi MH, Nassiri-Kashani M, Eskandari SE, Khatami A, Hooshmand B, Gorouhi F, Rashighi-Firoozabadi M, Dowlati Y (2006) Imiquimod in combination with meglumine antimoniate for cutaneous leishmaniasis: a randomized assessor-blind controlled trial. Arch Dermatol. 142(12): 1575–1579.

Hadighi R, Mohebali M, Boucher P, Haj-jaran H, Khamesipour A, Ouellette M (2006) Unresponsiveness to Glucantime treatment in Iranian cutaneous leishma-niasis due to drug-resistant Leishmania tropica parasites. PLoS Med. 3(5): 162–164.

Khatami A, Firooz A, Gorouhi F, Dowlati Y (2007) Treatment of acute Old World cutaneous leishmaniasis: a systematic review of the randomized controlled trials. J Am Acad Dermatol. 57(2): e1–e29.

Kazemi-Rad E, Mohebali M, Khadem-Erfan MB, Saffari M, Raoofian R, Hajjaran H, Hadighi R, Khamesipour A, Rezaie S, Abedkhojasteh H, Heidari M (2013) Identification of antimony resistance mar-kers in Leishmania tropica field isolates through a cDNA-AFLP approach. Exp Parasitol. 135(2): 344–349.

Croft S, Olliaro P (2011) Leishmaniasis chemotherapy-challenges and opportu-nities. Clin Microbiol Infect. 17(10): 1478–1483.

Jaafari MR, Khamesipour A (2015) Topi-cal liposomal compositions for delivering hydrophobic drugs and methods pre-paring same. Publication Number: US 2015/0147382 A1.

Draize JH, Woodard G, Calvery HO (1944) Methods for the study of irritation and toxicity of substances applied topically to the skin and mucous membranes. J Pharmacol Exp Ther. 82(3): 377–390.

Nixon GA, Tyson CA, Wertz WC (1975) Interspecies comparisons of skin irri-tancy. Toxicol Appl Pharmacol. 31(3): 481–490.

Griffith JF (1989) Use of human experience to calibrate Draize and in vitro eye test data. J Toxicol Cutaneous Ocul Toxi-col. 8(1): 23–34.

Vinardell M, Mitjans M (2008) Alter-native methods for eye and skin irri-tation tests: an overview. J Pharm Sci. 97(1): 46–59.

John FG (1989) Use of human experience to calibrate Draize and in vitro eye test data. Journal of Toxicology: Cutans Ocul Toxicol. 8(1): 23–34.

Shazad B, Abbaszadeh B, Khamesipour A (2005) Comparison of topical paro-momycin sulfate (twice/day) with int-ralesional meglumine antimoniate for the treatment of cutaneous leishmaniasis caused by L. major. Eur J Dermatol. 15 (2): 85–87.

Moosavian Kalat SM, Khamesipour A, Bavarsad N, Fallah M, Khashayarmanesh Z, Feizi E, Neghabi K, Abbasi A, Jaa-fari MR (2014) Use of topical liposomes containing meglumine antimoniate (Glu-cantime) for the treatment of L. major lesion in BALB/c mice. Exp Parasitol. 143: 5–10.

Khamesipour A, Abbasi A, Firooz A, Mohammadi AMA, Eskandari SE, Jaa-fari MR (2012) Treatment of cutaneous lesion of 20 yr’ duration caused by leishmanization. Indian J Dermatol. 57 (2): 123–125.

Khamesipour A (2014) Therapeutic vac-cines for leishmaniasis. Expert Opin-Biol Ther. 14(11): 1641–1649.

Published
2018-07-18
How to Cite
1.
Eskandari SE, Firooz A, Nassiri-Kashani M, Jaafari MR, Javadi A, Miramin-Mohammadi A, Valian-Keshavarz H, Khamesipour A. Safety Evaluation of Nano-Liposomal Formulation of Amphotericin B (SinaAmpholeish) in Animal Model as a Candidate for Treatment of Cutaneous Leishmaniasis. jad. 12(3):269-75.
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Original Article