Safety Evaluation of Topical Application of Nano-Liposomal Form of Amphotericin B (SinaAmpholeish) on Healthy Volunteers: Phase I Clinical Trial
Background: We aimed to evaluate the safety of SinaAmpholeish in a double-blind, randomized, phase 1 clinical trial in healthy human volunteers.
Methods: The study was carried out in DermaLab of Center for Research and Training in Skin Diseases and Leprosy, Tehran University of Medical Sciences, Tehran, Iran in 2012. A topical Nano-liposomal formulation of 0.4% Amphotericin B was developed against Leishmania under trade name of SinaAmpholeish. In this randomized, double-blind, right-left, comparative, phase I clinical trial, in 2 steps; 7 and 20 healthy volunteers were recruited and applied SinaAmpholeish on the right and its vehicle on the left volar side of forearm, twice a day for one week or 3 times a day for two weeks. Seven biophysical skin parameters were measured in standard conditions before and 2 wk after application.
Results: There was no adverse effect when SinaAmpholeish and its vehicle were used twice a day for seven days. However, when were used 3 times a day for two weeks, both SinaAmpholeish and its vehicle induced severe local skin reactions in 2 volunteers leading to discontinuation of application. Mild and temporary local reactions were observed in about half of the application sides and there was no significant difference between SinaAmpholeish and its vehicle.
Conclusion: The new formulation is safe and worth to be tested in further phase 2 clinical trial and since there was no adverse effect with twice a day application it was decided to use SinaAmpholeish twice a day in phase 2 clinical trial.
- Organization WH. Leishmaniasis Factsheet. World Health Organization. Available at: http://www.who.int/mediacentre/factsheets/fs375/en/
- Alvar J, Vélez ID, Bern C, Herrero M, Desjeux P, Cano J, et al. Leishmaniasis worldwide and global estimates of its incidence. PloS One. 2012;7(5):e35671.
- Postigo JA. Leishmaniasis in the World Health Organization Eastern Mediterranean Region. Int J Antimicrob Agents 2010; 36: S62-S65)
- Shirzadi MR. Statistics of cutaneous leishmanaisis in Iran: National Leishmaniasis Committee, Office of Zoonoses, Center of Disease Control, Ministry of Health and Medical Education. 1stMeeting of National Leishmaniasis Network (August 9, 2010).
- Mir Amin Mohammadi, A., Khamesipour, A., Khatami, A., Javadi, A., Nassiri-Kashani, M., Firooz, A., Dowlati, Y., Behnia, M., Eskandari, S.E.Cutaneous Leishmaniasis in suspected patients referred to the Center for Research and Training in Skin diseases and Leprosy, Tehran, Iran from 2008 to 2011. Iranian Journal of Parasitology, 2013, 8 (3) , pp. 430.
- Khatami A, Firooz A, Gorouhi F, Dowlati Y. Treatment of acute Old World cutaneous leishmaniasis: a systematic review of the randomized controlled trials. J Am Acad Dermatol. 2007;57(2):335. e1-e29.
- Firooz A, Khamesipour A, Ghoorchi MH, Nassiri-Kashani M, Eskandari SE, Khatami A, et al. Imiquimod in combination with meglumine antimoniate for cutaneous leishmaniasis: a randomized assessor-blind controlled trial. Arch Dermatol. 2006;142(12):1575-9.
- Hadighi R, Mohebali M, Boucher P, Hajjaran H, Khamesipour A, Ouellette M. Unresponsiveness to Glucantime treatment in Iranian cutaneous leishmaniasis due to drug-resistant Leishmania tropica parasites. PLoS Medicine. 2006;3(5):e162.
- Shazad B, Abbaszadeh B, Khamesipour A. Comparison of topical paromomycin sulfate (twice/day) with intralesional meglumine antimoniate for the treatment of cutaneous leishmaniasis caused by L. major. Eur J Dermatol. 2005;15(2):85-7.
- Khamesipour A, Abbasi A, Firooz A, Mohammadi AMA, Eskandari SE, Jaafari MR. Treatment of cutaneous lesion of 20 years’ duration caused by leishmanization. Indian J Dermatol. 2012;57(2):123.
- Wortmann G1, Zapor M, Ressner R, Fraser S, Hartzell J, Pierson J, Weintrob A, Magill A.Lipsosomal amphotericin B for treatment of cutaneous leishmaniasis. Am J Trop Med Hyg. 2010 Nov;83(5):1028-33. doi: 10.4269/ajtmh.2010.10-0171.
- Solomon M1, Pavlotsky F, Leshem E, Ephros M, Trau H, Schwartz E. Liposomal amphotericin B treatment of cutaneous leishmaniasis due to Leishmania tropica.J Eur Acad Dermatol Venereol. 2011 Aug;25(8):973-7. doi: 10.1111/j.1468-3083.2010.03908.x. Epub 2010 Dec 5.
- Khamesipour A. Therapeutic vaccines for leishmaniasis. Expert OpinBiol Ther. 2014;14(11):1641-9.
- Jaafari MR, Khamesipour A. Topical liposomal compositions for delivering hydrophobic drugs and methods preparing same. The United States Patent Application Publication. Publication Number: US 2015/0147382 A1; Pub. Date: May 28, 2015.
- Jaafari MR, Hatamipour M, Abbasi A, Saberi Z, Alavizadeh SH, Rafati S, Taslimi Y, et. al. Development of topical liposomal formulation of Amphotericin B for the treatment of cutaneous leishmaniasis. Antimicrob Agents Chemother. 2017 (submitted).
- Eskandari S, Firooz AR, Nassiri-Kashani M, Jaafari MR, Javadi A, Miramin Mohamadi A, Khamesipour A. Safety evaluation of liposomal formulation of Amphotericin B in animal model using for the treatment cutaneous leishmaniasis. Arthopod born Diseases 2017.
- Modabber F, Buffet PA, Torreele E, et al. Consultative meeting to develop a strategy for treatment of cutaneous leishmaniasis. Institute Pasteur, Paris. 13-15 June, 2006.
- Moosavian Kalat SM, Khamesipour A, Bavarsad N, Fallah M, Khashayarmanesh Z, Feizi E, et al. Use of topical liposomes containing meglumine antimoniate (Glucantime) for the treatment of L. major lesion in BALB/c mice. Exp Parasitol. 2014;143:5-10.
- Grogl M, Schuster BG, Ellis WY, Berman JD. Successful topical treatment of murine cutaneous leishmaniasis with a combination of paromomycin (Aminosidine) and gentamicin. J Parasitol. 1999 Apr;85(2):354-9.
- Kim DH, Chung HJ, Bleys J, Ghohestani RF. Is paromomycin an effective and safe treatment against cutaneous leishmaniasis? A meta-analysis of 14 randomized controlled trials. PLoS Negl Trop Dis. 2009;3(2):e381.
- Nigam P. Adverse reactions to cosmetics and methods of testing. Indian Journal of Dermatology, Venereology, and Leprology. 2009;75(1):10.
- ICH Harmonised Tripartite Guideline. General Considerations For Clinical Trials. Recommended For Adoption At Step 4 Of The ICH Process On 17 July 1997.
- Firooz A, et al. Variation of biophysical parameters of the skin with age, gender, and body region. ScientificWorldJournal. 2012;2012:386936.
- Agnes MH, et al. Skin hydration and cooling effect produced by the Voltaren® vehicle gel. Skin Research and Technology 2012; 18: 199–206.
|Issue||Vol 14 No 2 (2019)|
|Safety Topical formulation Nano-liposomal amphoter-icin B Cutaneous leishmaniasis|
|Rights and permissions|
|This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.|