Formulation and Clinical Evaluation of Ethosomal and Liposomal Preparations of Anthralin in Psoriasis

Psoriasis Vulgaris Clinical Trial

Official title:

Formulation and Clinical Evaluation of Ethosomal and Liposomal Preparations of Anthralin in Psoriasis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03348462
• Other study ID #: faceoealpoaip
• Status: Completed
• Phase: Phase 4
• Start date: November 30, 2017
• Est. completion date: January 15, 2020

Study information

• Verified date: March 2020
• Source: Assiut University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Psoriasis is a common immune mediated inflammatory skin disease characterized by red heavily scaled plaques. Anthralin (1,8-dihydroxy-9-anthrone) which was introduced over 80 years ago has shown excellent efficacy in the management of psoriasis.Although anthralin is remarkably effective in the management of psoriasis, its side effects are equally disturbing. Its use is messy as it stains the skin, clothing, and any furniture that it may come in contact with. Further, anthralin has irritating, burning, brown discoloration and necrotizing effect on the normal and the diseased skin. This troublesome profile has discouraged wide-spread use of the drug.

Ethosomes are attractive vesicular carriers mainly composed of phospholipids, ethanol and water. The intriguing features of ethosomes are due to their high ethanol content which facilitate their penetration through stratum corneum and target deep skin layers. This is advantageous over conventional liposomes which have limited penetration through the skin and remain confined in the upper layer of the stratum corneum. Compared to liposomes, ethosomes had greater retention of methotrexate into the skin for a longer period of time, suggesting better therapeutic outcome.

Description:

Psoriasis is a common immune mediated inflammatory skin disease characterized by red heavily scaled plaques. Anthralin (1,8-dihydroxy-9-anthrone) which was introduced over 80 years ago has shown excellent efficacy in the management of psoriasis.Anthralin mechanism of action involves inhibition of the proliferation of keratinocytes. Further, accumulation of anthralin inside the mitochondria impairs energy supply to the cell, probably due to the free radicals resulting from oxidation of the drug. Anthralin also interferes with the replication of DNA and slows down the extreme cell division that occurs in psoriatic plaques. Although anthralin is remarkably effective in the management of psoriasis, its side effects are equally disturbing. Its use is messy as it stains the skin, clothing, and any furniture that it may come in contact with. Further, anthralin has irritating, burning, brown discoloration and necrotizing effect on the normal and the diseased skin. This troublesome profile has discouraged wide-spread use of the drug.

Ethosomes are attractive vesicular carriers mainly composed of phospholipids, ethanol and water. The intriguing features of ethosomes are due to their high ethanol content which facilitate their penetration through stratum corneum and target deep skin layers. This is advantageous over conventional liposomes which have limited penetration through the skin and remain confined in the upper layer of the stratum corneum. Compared to liposomes, ethosomes had greater retention of methotrexate into the skin for a longer period of time, suggesting better therapeutic outcome.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: January 15, 2020
• Est. primary completion date: December 30, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 9 Years to 70 Years

Eligibility

Inclusion Criteria:

• patients with mild to moderate, stable chronic plaque psoriasis.

Exclusion Criteria:

• patients with severe psoriasis.

• Patients received any topical or systemic treatment for psoriasis one month before the start of the study.

Related Conditions & MeSH terms

• Psoriasis
• Psoriasis Vulgaris

Intervention

Drug:
• ethosomal preparation of anthralin
once daily with short contact topical application
• liposomal preparation of anthralin
once daily with short contact topical application

Locations

Country	Name	City	State
Egypt	Assiut University Hospital	Assiut

Sponsors (1)

Lead Sponsor	Collaborator
Assiut University

Country where clinical trial is conducted

Egypt, 

References & Publications (10)

Agarwal R, Katare OP, Vyas SP. Preparation and in vitro evaluation of liposomal/niosomal delivery systems for antipsoriatic drug dithranol. Int J Pharm. 2001 Oct 9;228(1-2):43-52. — View Citation

Dubey V, Mishra D, Dutta T, Nahar M, Saraf DK, Jain NK. Dermal and transdermal delivery of an anti-psoriatic agent via ethanolic liposomes. J Control Release. 2007 Nov 6;123(2):148-54. Epub 2007 Aug 16. — View Citation

Hollywood KA, Winder CL, Dunn WB, Xu Y, Broadhurst D, Griffiths CE, Goodacre R. Exploring the mode of action of dithranol therapy for psoriasis: a metabolomic analysis using HaCaT cells. Mol Biosyst. 2015 Aug;11(8):2198-209. doi: 10.1039/c4mb00739e. — View Citation

McGill A, Frank A, Emmett N, Turnbull DM, Birch-Machin MA, Reynolds NJ. The anti-psoriatic drug anthralin accumulates in keratinocyte mitochondria, dissipates mitochondrial membrane potential, and induces apoptosis through a pathway dependent on respiratory competent mitochondria. FASEB J. 2005 Jun;19(8):1012-4. Epub 2005 Mar 31. — View Citation

Mendonça CO, Burden AD. Current concepts in psoriasis and its treatment. Pharmacol Ther. 2003 Aug;99(2):133-47. Review. — View Citation

Parish LC, Millikan LE, Witkowski JA. The modern story of anthralin. Int J Dermatol. 1989 Jul-Aug;28(6):373-4. — View Citation

Pradhan M, Singh D, Singh MR. Novel colloidal carriers for psoriasis: current issues, mechanistic insight and novel delivery approaches. J Control Release. 2013 Sep 28;170(3):380-95. doi: 10.1016/j.jconrel.2013.05.020. Epub 2013 Jun 13. Review. — View Citation

Saraswat A, Agarwal R, Katare OP, Kaur I, Kumar B. A randomized, double-blind, vehicle-controlled study of a novel liposomal dithranol formulation in psoriasis. J Dermatolog Treat. 2007;18(1):40-5. — View Citation

Sehgal VN, Verma P, Khurana A. Anthralin/dithranol in dermatology. Int J Dermatol. 2014 Oct;53(10):e449-60. doi: 10.1111/j.1365-4632.2012.05611.x. Epub 2014 Sep 10. Review. — View Citation

Touitou E, Dayan N, Bergelson L, Godin B, Eliaz M. Ethosomes - novel vesicular carriers for enhanced delivery: characterization and skin penetration properties. J Control Release. 2000 Apr 3;65(3):403-18. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Psoriasis Area and Severity Index (PASI) score	PASI combines the assessment of the severity of psoriatic lesions and the area affected into a single score in the range 0 (no disease) to 72 (maximal disease). PASI will be measured before and after treatment to assess the efficacy of therapy.Steps in generating PASI score; Divide body into four areas: head, arms, trunk, and legs .; Generate an average score for the erythema, thickness, and scaling for each of the 4 areas , each graded on a 0-4 scale (0 = clear, 1= slight,2= mild, 3=moderate, 4=severe).; Sum scores of erythema, thickness, and scale for each area.; Generate a percentage for skin covered with psoriasis for each area and convert that to a 0-6 scale (0 = 0%; 1 =,10%; 2 = 10-,30%; 3 = 30-,50%; 4 = 50-; ,70%; 5 = 70-,90%; 6 = 90-100%).; Multiply score of item (c) above times item (d) above for each area and multiply that by 0.1, 0.2, 0.3, and 0.4 for head, arms, trunk, and legs, respectively.; Add these scores to get the PASI score.	up to 8 weeks
Secondary	Histopathological examination of psoriatic lesions using hematoxylin and eosin staining (H & E stain)	hematoxylin and eosin staining of skin biopsies from psoriatic lesions before and after treatment will be done.	up to 8 weeks
Secondary	Safety of the drug perparations	by recording any possible adverse events like itching, burning sensation, staining of skin or clothes and erythema.	up to 8 weeks
Secondary	Patient satisfaction	at the end of treatment, it will be evaluated by patient's self assessment of the degree of improvement of psoriasis	up to 8 weeks
Secondary	digital photography	digital photography of the lesions before and after treatment using a 14.1 megapixels Sony DSC- W 390 digital camera will be done for each patient to assess any changes in clinical appearance of psoriatic lesions and evaluate the response of treatment.	up to 8 weeks

External Links

•   Nanotechnology in dermatology