Ignite Creation Date:
2024-10-26 @ 3:36 PM
Last Modification Date:
2024-10-26 @ 3:36 PM
Study NCT ID:
NCT06527729
Status:
COMPLETED
Last Update Posted:
None
First Post:
2024-07-14
Brief Title:
A Novel Formulation of Sildenafil-loaded Nanocarriers for Treatment of Alopecia Areata
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Sildenafil-loaded Lipid-based Nanocarrier as a Potential Therapy for Alopecia Areata A Randomized Clinical Study
Status:
COMPLETED
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Alopecia areata AA is a common cause of nonscarring alopecia that occurs in a patchy confluent or diffuse pattern Many theories were implicated in pathogenesis of AA such as an autoimmune lymphocytic attack of the hair genetic basis and environmental factors Clinically AA presents as a well-circumscribed patch of sudden hair loss It affects any hair bearing area with the scalp being the most commonly affected site
Dermoscopy is a noninvasive technique for the clinical diagnosis of many skin diseases Dermoscopy is now considered as a valuable tool in diagnosis of variable skin lesions Scalp dermoscopy Trichoscopy does not only facilitate diagnosis of hair disorders but also give clues about disease stage and progression
The most common trichoscopic features of AA are yellow dots micro-exclamation mark hairs tapered hairs black dots broken hairs and regrowing upright or regrowing coiled hairs Trichoscopic characteristics have a clinical significance in AA for diagnosis and prognosis
The treatment of alopecia areata involves promotion of hair growth for instance with topical minoxidil application immunosuppression intralesional or systemic steroid therapy phototherapy or immunomodulation anthralin dinitrochlorobenzene diphenylcyclopropenone squaric acid dibutylesterUnfortunately there is currently no cure for this chronic disease and despite the presence of a wide variety of therapeutic options none is universally proven to induce andor sustain remission Development of new drugs and formulations is urgently needed
Sildenafil a phosphodiesterase 5 PDE5 inhibitor is known to increase the intracellular level of cyclic guanosine monophosphate cGMP which causes vasodilation Sildenafil was first approved in 1998 for erectile dysfunction but since then additional uses for the drug have been found A previous study demonstrated the significant therapeutic potential of sildenafil on hair growth and proposed its potential use in treatment of alopecia It has been shown that it enhances proliferation of human dermal papilla cells hDPCs and up-regulates the mRNA expression of vascular endothelial growth factor VEGF and platelet-derived growth factor PDGF which are responsible for hair growth Additionally sildenafil up-regulates the levels of phosphorylated ERK and accelerates anagen induction by stimulating perifollicular vessel formation after topical application in mice
Dermoscopy is a noninvasive technique for the clinical diagnosis of many skin diseases Dermoscopy is now considered as a valuable tool in diagnosis of variable skin lesions Scalp dermoscopy Trichoscopy does not only facilitate diagnosis of hair disorders but also give clues about disease stage and progression
The most common trichoscopic features of AA are yellow dots micro-exclamation mark hairs tapered hairs black dots broken hairs and regrowing upright or regrowing coiled hairs Trichoscopic characteristics have a clinical significance in AA for diagnosis and prognosis
The treatment of alopecia areata involves promotion of hair growth for instance with topical minoxidil application immunosuppression intralesional or systemic steroid therapy phototherapy or immunomodulation anthralin dinitrochlorobenzene diphenylcyclopropenone squaric acid dibutylesterUnfortunately there is currently no cure for this chronic disease and despite the presence of a wide variety of therapeutic options none is universally proven to induce andor sustain remission Development of new drugs and formulations is urgently needed
Sildenafil a phosphodiesterase 5 PDE5 inhibitor is known to increase the intracellular level of cyclic guanosine monophosphate cGMP which causes vasodilation Sildenafil was first approved in 1998 for erectile dysfunction but since then additional uses for the drug have been found A previous study demonstrated the significant therapeutic potential of sildenafil on hair growth and proposed its potential use in treatment of alopecia It has been shown that it enhances proliferation of human dermal papilla cells hDPCs and up-regulates the mRNA expression of vascular endothelial growth factor VEGF and platelet-derived growth factor PDGF which are responsible for hair growth Additionally sildenafil up-regulates the levels of phosphorylated ERK and accelerates anagen induction by stimulating perifollicular vessel formation after topical application in mice
Detailed Description:
The aim of the present work was to optimize sildenafil-loaded liposomes which could enhance percutaneous absorption and follicular penetration of sildenafil achieving improved therapeutic efficiency with minimal unnecessary side effects due to oral administration
In addition the study aimed to assess the efficacy of topical sildenafil-loaded liposomes formulation compared with topical minoxidil therapy for the treatment of patchy AA of the scalp through examination of its clinical effects along with dermoscopic findings
Materials Lipoid S75 phosphatidylcholine 70 with fat-free soybean phospholipids was kindly donated by lipoid company Germany Sildenafil citrate was purchased from Fagron Iberica SAU Acetonitrile HPLC reagent was purchased from Fisher Chemical Ultrapure water was Cholesterol was purchased from Fluka chemical co India Ethanol absolute was purchased from El-Nasr Pharmaceuticals Egypt All reagents and chemicals were purchased from Sigma Aldrich
Methodology Preparation of SIL-LIP using spraying technique SIL-LIP were formulated using spraying method Pre-calculated amounts of Lipoid s75 cholesterol and sildenafil were dissolved in 2 ml of absolute ethanol and the prepared solution was transferred to a spraying apparatus 20 In a closed system the alcoholic solution of sildenafil and lipids was sprayed 100 ul were sprayed every 10 seconds onto the surface of 2 ml distilled water containing sucrose 9 wv with stirring at 1250 rpm at 25ยบ C Stirring was maintained until complete evaporation of ethanol To guarantee complete annealing of the formed liposomes SIL-LIP were kept at 4C overnight 21 SIL-LIP were imaged using JEM-1400-Jeol-Tokyo-Japan maintained at 80-kV SIL-LIP was-left for ten minutes at 25C before examination on carbon-coated-copper-grid
Particle size measurement To gain more insight into size and size distribution laser light diffraction was employed the Prepared SIL-LIP were diluted with deionized water and was analyzed with Mastersizer 3000E Malvern Instruments UK at 25C The result was the average of three repeated values
Entrapment efficiency EE of prepared liposomes
The EE was determined by centrifugation of liposomal suspension at 1000 rpm for 45 min at 4 C to isolate the unentrapped sildenafil in the supernatant for indirect determination of EE The amount of sildenafil in the supernatant was determined by UV spectrophotometer Spectronic Genesys Winspec Software Spectronic USA at 228 nm EE was calculated as follows
EE Qi -QsQt 100 where Qi is the initial amount of the sildenafil added during preparation and Qs is the sildenafil amount determined in the supernatant after centrifugation Clinical study A prospective randomized controlled study was conducted in the department of Dermatology Assiut University Hospital including patients with patchy AA of scalp aged between 10 and 40 years Patients having alopecia totalisuniversalis or ophiasis those with systemic andor other dermatological diseases and those receiving treatment for AA in the previous 3 months were excluded
This study was conducted in compliance with the guidelines of the Declaration of Helsinki and the study protocol was approved by the Research Ethics Committee of Faculty of Medicine Assiut University IRB no 17300458 Informed consent was obtained from all patients before enrolments
At the initial visit full history taking and thorough clinical examination was done for all patients The diagnosis was established based on both clinical and dermoscopic examination
Treatment Protocol
Patients were randomly assigned to use either topical 5 minoxidil gel or topical 1 sildenafil-loaded liposomes twice daily for a period of 8 weeks
Assessment criteria
Clinical evaluation was performed by the comparison of serial photographs of the lesions to the baseline ones Severity of Alopecia Tool SALT score was calculated at baseline 4 weeks and 8 weeks and the average percentage of hair re-growth was determined using the SALT scoring system for hair re-growth and graded as A0 no change or further hair loss A1 1-24 hair re-growth A2 25-49 hair re-growth A3 50-74 hair regrowth A4 75-99 hair re-growth and A5 100 hair re-growth
Dermoscopic examination was carried out before treatment and at 4 and 8 weeks using the handheld dermoscope DermLite DL4 3Gen Inc San Juan Capistrano CA 92675 Baseline and post-therapy digital photographs of dermoscopic fields were taken using an iPhone 6S smartphone camera Dermoscopic features of AA were evaluated including yellow dots black dots broken hair exclamation-mark hairs short vellus hair and regrowing hair Two dermoscopic fields were examined one from the center and the other at 3 oclock position of the alopecia patch Trichoscopic parameters in each field were evaluated and quantified
Data analysis was done using the SPSS software version 24 SPSS Inc Chicago IL USA The Chi-square test and Mann-Whitney test were used for comparison of qualitative data and quantitative data respectively P 005 was considered statistically significant
In addition the study aimed to assess the efficacy of topical sildenafil-loaded liposomes formulation compared with topical minoxidil therapy for the treatment of patchy AA of the scalp through examination of its clinical effects along with dermoscopic findings
Materials Lipoid S75 phosphatidylcholine 70 with fat-free soybean phospholipids was kindly donated by lipoid company Germany Sildenafil citrate was purchased from Fagron Iberica SAU Acetonitrile HPLC reagent was purchased from Fisher Chemical Ultrapure water was Cholesterol was purchased from Fluka chemical co India Ethanol absolute was purchased from El-Nasr Pharmaceuticals Egypt All reagents and chemicals were purchased from Sigma Aldrich
Methodology Preparation of SIL-LIP using spraying technique SIL-LIP were formulated using spraying method Pre-calculated amounts of Lipoid s75 cholesterol and sildenafil were dissolved in 2 ml of absolute ethanol and the prepared solution was transferred to a spraying apparatus 20 In a closed system the alcoholic solution of sildenafil and lipids was sprayed 100 ul were sprayed every 10 seconds onto the surface of 2 ml distilled water containing sucrose 9 wv with stirring at 1250 rpm at 25ยบ C Stirring was maintained until complete evaporation of ethanol To guarantee complete annealing of the formed liposomes SIL-LIP were kept at 4C overnight 21 SIL-LIP were imaged using JEM-1400-Jeol-Tokyo-Japan maintained at 80-kV SIL-LIP was-left for ten minutes at 25C before examination on carbon-coated-copper-grid
Particle size measurement To gain more insight into size and size distribution laser light diffraction was employed the Prepared SIL-LIP were diluted with deionized water and was analyzed with Mastersizer 3000E Malvern Instruments UK at 25C The result was the average of three repeated values
Entrapment efficiency EE of prepared liposomes
The EE was determined by centrifugation of liposomal suspension at 1000 rpm for 45 min at 4 C to isolate the unentrapped sildenafil in the supernatant for indirect determination of EE The amount of sildenafil in the supernatant was determined by UV spectrophotometer Spectronic Genesys Winspec Software Spectronic USA at 228 nm EE was calculated as follows
EE Qi -QsQt 100 where Qi is the initial amount of the sildenafil added during preparation and Qs is the sildenafil amount determined in the supernatant after centrifugation Clinical study A prospective randomized controlled study was conducted in the department of Dermatology Assiut University Hospital including patients with patchy AA of scalp aged between 10 and 40 years Patients having alopecia totalisuniversalis or ophiasis those with systemic andor other dermatological diseases and those receiving treatment for AA in the previous 3 months were excluded
This study was conducted in compliance with the guidelines of the Declaration of Helsinki and the study protocol was approved by the Research Ethics Committee of Faculty of Medicine Assiut University IRB no 17300458 Informed consent was obtained from all patients before enrolments
At the initial visit full history taking and thorough clinical examination was done for all patients The diagnosis was established based on both clinical and dermoscopic examination
Treatment Protocol
Patients were randomly assigned to use either topical 5 minoxidil gel or topical 1 sildenafil-loaded liposomes twice daily for a period of 8 weeks
Assessment criteria
Clinical evaluation was performed by the comparison of serial photographs of the lesions to the baseline ones Severity of Alopecia Tool SALT score was calculated at baseline 4 weeks and 8 weeks and the average percentage of hair re-growth was determined using the SALT scoring system for hair re-growth and graded as A0 no change or further hair loss A1 1-24 hair re-growth A2 25-49 hair re-growth A3 50-74 hair regrowth A4 75-99 hair re-growth and A5 100 hair re-growth
Dermoscopic examination was carried out before treatment and at 4 and 8 weeks using the handheld dermoscope DermLite DL4 3Gen Inc San Juan Capistrano CA 92675 Baseline and post-therapy digital photographs of dermoscopic fields were taken using an iPhone 6S smartphone camera Dermoscopic features of AA were evaluated including yellow dots black dots broken hair exclamation-mark hairs short vellus hair and regrowing hair Two dermoscopic fields were examined one from the center and the other at 3 oclock position of the alopecia patch Trichoscopic parameters in each field were evaluated and quantified
Data analysis was done using the SPSS software version 24 SPSS Inc Chicago IL USA The Chi-square test and Mann-Whitney test were used for comparison of qualitative data and quantitative data respectively P 005 was considered statistically significant
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None