Evaluation the Topical Apremilast Nanoformulation in Treatment of Localized Plaque Psoriasis

March 2, 2026 updated by: Aliaa Effat Saied Sayed, Assiut University

Evaluation of Topical Apremilast Nanoparticles in the Treatment of Plaque Psoriasis: Clinical, Histopathological and Immunohistochemical Study

This study is a comparative randomized clinical trial evaluating the efficacy and safety of topical apremilast nanoemulsion 0.3% in the treatment of localized mild to moderate plaque psoriasis.Clinical efficacy will be assessed using TES score, Physician Global Assessment (PGA), dermoscopy, and patient satisfaction, while safety is monitored through adverse effect reporting. In addition, histopathological and immunohistochemical evaluation of PDE4 expression will be performed before and after treatment to assess tissue-level responses.

The study aims to determine whether topical apremilast nano-formulation, alone or combined with corticosteroids, offers an effective and safer alternative to conventional topical therapy, with improved local efficacy and reduced corticosteroid-related adverse effects.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Psoriasis is a chronic immune-mediated inflammatory skin condition with a strong genetic predisposition and an autoimmune pathogenic characteristic . Its worldwide prevalence is up to 2% but this varies between different geographic regions . In Egypt, the prevalence of psoriasis ranges between 0.19% and 3% .

Individuals with psoriasis frequently endure marked psychological distress. This includes social embarrassment, reduced self esteem, anxiety, depression, and an increased tendency toward suicidal ideation and behavior .

Psoriasis Skin lesions are usually symmetrical, sharply demarcated, with red or pink raised plaques, and covered with silvery scales. These plaques reflect key pathological processes, including inflammation, keratinocyte hyperproliferation, and angiogenesis .

Cellular responses to environmental stimuli and intracellular signaling in various cell types-including myeloid, lymphoid, and other inflammatory cells-are mediated by intracellular "second messengers," particularly cyclic adenosine monophosphate (cAMP) .

Phosphodiesterase4 (PDE4) is one of the major cAMP-selective PDEs expressed in epithelial cells . It is also present in several mesenchymal cell types, including dermal keratinocytes, smooth muscle cells, vascular endothelial cells, and chondrocytes, By decreasing intracellular cAMP, PDE4 promotes production of pro-inflammatory mediators and decreases production of anti-inflammatory mediators. Conversely, inhibition of PDE4 increases the intracellular concentration of cAMP and selectively blocks pro-inflammatory cytokines, such as TNF-α, IFN-γ, and IL-2 production from peripheral blood monocytes and T cells.

PDE4 has four subtypes (A, B, C and D). These subtypes are encoded on separate genes. Expression of the PDE4A subtype increased in nearly all cell types of the skin of psoriasis patients. PDE4B is present in vessels and in immune cells, whereas PDE4D is expressed in fibroblasts and endothelial cells .

Management of mild to moderate psoriasis usually begins with topical therapies, including emollients, topical corticosteroids, calcipotriol, tar preparations, and dithranol. There is little evidence to guide the selection of topical treatments, so it can be based on patient and prescriber preference .

Topical glucocorticoids are the first-line therapy in mild to moderate psoriasis and areas where other topical treatments may cause irritation, such as joints or genitals . Corticosteroids bind to intracellular corticosteroid receptor and regulate gene transcription of numerous genes, particularly those that code for pro-inflammatory cytokines. They act as vasoconstrictive, antiproliferative, anti-inflammatory and immunosuppressive.

However, long-term application of topical corticosteroids may cause skin atrophy, striae, telangiectasia, adrenal suppression and hypopigmentation. Additionally, abrupt discontinuation can precipitate early disease relapse or rebound flares.

Apremilast is classified as a small-molecule phosphodiesterase4 (PDE4) inhibitor , It inhibits PDE4 isoforms from all four sub-families (A,B,C,D) Apremilast acts by hindering the conversion of cyclic adenosine monophosphate (cAMP) to AMP . further causing an intracellular accumulation of cyclic adenosine monophosphate (cAMP) causing a reduction in the production of inflammatory mediators such as CX-CL9, CX-CL10, IFN-γ, TNF-α, IL-2, IL-8, IL-12, and IL-23, thereby attenuating the inflammatory cascade .

Its oral form is FDA approved for plaque psoriasis in adult patients eligible for systemic therapy or phototherapy, as well as for adults with moderately to severely active psoriatic arthritis. . It is recommended that apremilast be titrated to the recommended dose of 30 mg twice daily, to be taken orally starting on day 6 .

The results of long-term, placebo-controlled study (ESTEEM 2) established the efficacy of oral apremilast in patients with plaque psoriasis, and are consistent with those reported in ESTEEM 1.The primary end point in this study was met, with a significantly greater proportion of patients treated with apremilast achieving a PASI 75 response at week 16 vs. placebo. Across different phases of study, PASI 75 responses at week 16 have ranged from 29% to 41%.

Apremilast is low soluble and low permeable classifying the drug as biopharmaceutical classification system (BCS) class 4 molecule with a poor solubility of 10-14 μg/mL. The oral medication of apremilast has systemic side effects such as diarrhea, nausea, vomiting, weight loss, and depression in some cases .

These limitations highlight the need for alternative routes of administration that enhance drug delivery to affected skin while minimizing systemic exposure. Topical delivery of apremilast represents a promising strategy to achieve localized therapeutic effects with fewer systemic side effects and improve patient outcomes .

Nevertheless, poor solubility and limited skin penetration restrict the effectiveness of topical apremilast, particularly in psoriatic skin, which is thickened and inflamed . Hence, the incorporation into nanotechnology-based drug delivery systems could be used as a strategy to improve its solubility and permeability in order to improve dermal bioavailability and consequently to achieve local anti-inflammatory efficacy .

Several ex vivo studies have demonstrated that apremilast loaded nanoparticles significantly increase skin retention compared with conventional gel formulations, resulting in improved therapeutic outcomes. Cytotoxicity and skin irritation studies further indicate that nano formulations are safe and well tolerated .

Study Type

Interventional

Enrollment (Estimated)

36

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age: ≥18 years.
  • Pattern: Patients with chronic plaque psoriasis not exceeding 10% of the body surface area.

Exclusion Criteria:

  • History of phototherapy or systemic treatment in the previous 12 weeks, topical psoriasis treatment within the last 4 weeks.
  • Renal, hepatic disease, cardiovascular, Immunosuppressive therapy, endocrine and blood disease or mental illness.
  • Pregnancy, breast-feeding or women planning to become pregnant within 3 months.
  • Psoriasis exceeding 10% of body surface area or other severe types of psoriasis requiring systemic treatment.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Topical Apremilast Nanoformula
Participants will receive topical apremilast nanoformula 0.3% applied twice daily for 12 weeks.
Drug: Apremilast Nanoformula 0.3٪
the nano based formula of apremilast will be prepared from its raw powder at Assuit international center of nanomedicine, Alrajhy Liver hospital, Assuit university. Nanoparticles loaded-apremilast 0.3% will be filled into sealed containers labeled as (number 1) and provided to patients and they will be instructed to apply thin a film twice daily for 12 weeks
Active Comparator: Topical betamethasone valerate
Participants will receive topical betamethasone valerate 0.1% cream applied twice daily for 12 weeks.
Drug: betamethasone valerate 0.1% cream
• Betamethsone valerate cream 0.1%: The commercially available betamethasone valerate cream will be re-packaged into identical, non-identifiable containers labeled (number 2 ) in order to ensure patient blinding and it will be applied twice daily for 12 weeks
Experimental: Combination therapy
Participants will receive combined topical apremilast nanoformula 0.3% and topical betamethasone valerate 0.1% cream applied for 12 weeks.
Drug: Apremilast Nanoformula 0.3٪
the nano based formula of apremilast will be prepared from its raw powder at Assuit international center of nanomedicine, Alrajhy Liver hospital, Assuit university. Nanoparticles loaded-apremilast 0.3% will be filled into sealed containers labeled as (number 1) and provided to patients and they will be instructed to apply thin a film twice daily for 12 weeks
Drug: betamethasone valerate 0.1% cream
• Betamethsone valerate cream 0.1%: The commercially available betamethasone valerate cream will be re-packaged into identical, non-identifiable containers labeled (number 2 ) in order to ensure patient blinding and it will be applied twice daily for 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Psoriasis thickness,erythema, and scaling (TES score) from baseline to Week 12
Time Frame: Baseline to week 12 and two months after to detect recurrence .
To evaluate the efficacy and safety of topical apremilast nanoemulsion 0.3٪ for treatment of localized plaque psoriasis as a monotherapy versus topical betamethasone valerate 0.1٪ cream alone and its combination with a topical betamethasone valerate 0.1٪ cream
Baseline to week 12 and two months after to detect recurrence .

Secondary Outcome Measures

Outcome Measure
Time Frame
Change in dermoscopic features of psoriatic plaques from baseline to Week 12
Time Frame: Baseline to week 12
Baseline to week 12
Change in histopathological features of psoriatic plaques from baseline to Week 12
Time Frame: Baseline to week 12
Baseline to week 12
Change in immunohistochemical expression of PDE4( B/C/D) from baseline to Week 12
Time Frame: Baseline to week 12
Baseline to week 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assiut University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

May 1, 2026

Primary Completion (Estimated)

May 1, 2027

Study Completion (Estimated)

March 1, 2028

Study Registration Dates

First Submitted

January 10, 2026

First Submitted That Met QC Criteria

January 16, 2026

First Posted (Actual)

January 26, 2026

Study Record Updates

Last Update Posted (Actual)

March 3, 2026

Last Update Submitted That Met QC Criteria

March 2, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Nano Apremilast in psoriasis

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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