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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Psoriasis Vulgaris

Intervention / Treatment
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* Drug: ethosomal preparation of anthralin
* Drug: liposomal preparation of anthralin


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 9 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The aim of the present study was to develop an ethosomal delivery system anthralin and evaluate its effectiveness and safety in treatment of psoriasis and comparing it with liposomal delivery system anthralin.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ethosomal anthralin<br>Group 1: included 10 psoriatic patients will be treated with ethosomal preparation of anthralin. Patients will be treated with this preparation with short contact (only one hour) daily up to 8 weeks. | Drug: ethosomal preparation of anthralin<br>* once daily with short contact topical application<br>|
| Active Comparator: liposomal anthralin<br>Group 2: included 10 psoriatic patients will be treated with liposomal preparation of anthralin. Patients will be treated with this preparation with short contact (only one hour) daily up to 8 weeks. | Drug: liposomal preparation of anthralin<br>* once daily with short contact topical application<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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psoriasis, anthralin, ethosome, liposome