A novel topical combination of minoxidil and spironolactone for androgenetic alopecia: Clinical, histopathological, and physicochemical study.

Topical minoxidil 5% are effective in androgenetic alopecia (AGA). Spironolactone acts as an androgen antagonist by competitively blocking androgen receptors. Studying the effect of topical minoxidil 5% gel and spironolactone gel 1% in management of AGA. The study includes 60 patients diagnosed as AGA; (group I): treated with topical minoxidil gel 5%, (group II): with topical spironolactone gel 1% and group (III) treated with combined minoxidil 5% and spironolactone 1% gel. All patients were followed up monthly throughout the treatment period. Scalp biopsy was taken before and after 12 months. In group I, the clinical response was in 90% of patients with variable degrees in improvement, in group II, the clinical response was in 80% of patients, meanwhile, in group III the clinical response was in all patients (100%). Histopathological examination of skin biopsy after treatment revealed significant increase in anagen hair on the other hand, both telogen and vellus hair was significantly decreased meanwhile, the T/V ratio was significantly increased. The results of this work revealed that topical minoxidil gel 5% and topical spironolactone gel 1% were effective in treatment of AGA, while the combination of two agents was better in treatment.

Topical antibiotics limit depigmentation in a mouse model of vitiligo.

Oral neomycin administration impacts the gut microbiome and delays vitiligo development in mice, and topical antibiotics may likewise allow the microbiome to preserve skin health and delay depigmentation. Here, we examined the effects of 6-week topical antibiotic treatment on vitiligo-prone pmel-1 mice. Bacitracin, Neosporin, or Vaseline were applied to one denuded flank, while the contralateral flank was treated with Vaseline in all mice. Ventral depigmentation was quantified weekly. We found that topical Neosporin treatment significantly reduced depigmentation and exhibited effects beyond the treated area, while Bacitracin ointment had no effect. Stool samples collected from four representative mice/group during treatment revealed that Neosporin treatment aligned with reduced abundance of the Alistipes genus in the gut, while relevant changes to the skin microbiome at end point were less apparent. Either antibiotic treatment led to reduced expression of MR1, potentially limiting mucosal-associated invariant T-cell activation, while Neosporin-treated skin selectively revealed significantly reduced CD8+ T-cell abundance. The latter finding aligned with reduced expression of multiple inflammatory markers and markedly increased regulatory T-cell density. Our studies on favorable skin and oral antibiotic treatment share the neomycin compound, and in either case, microbial changes were most apparent in stool samples. Taken together, neomycin-containing antibiotic applications can mediate skin Treg infiltration to limit vitiligo development. Our study highlights the therapeutic potential of short-term antibiotic applications to limit depigmentation vitiligo.

Melanocyte-keratinocyte cross-talk in vitiligo.

Vitiligo is a common acquired pigmentary disorder that presents as progressive loss of melanocytes from the skin. Epidermal melanocytes and keratinocytes are in close proximity to each other, forming a functional and structural unit where keratinocytes play a pivotal role in supporting melanocyte homeostasis and melanogenesis. This intimate relationship suggests that keratinocytes might contribute to ongoing melanocyte loss and subsequent depigmentation. In fact, keratinocyte dysfunction is a documented phenomenon in vitiligo. Keratinocyte apoptosis can deprive melanocytes from growth factors including stem cell factor (SCF) and other melanogenic stimulating factors which are essential for melanocyte function. Additionally, keratinocytes control the mobility/stability phases of melanocytes via matrix metalloproteinases and basement membrane remodeling. Hence keratinocyte dysfunction may be implicated in detachment of melanocytes from the basement membrane and subsequent loss from the epidermis, also potentially interfering with repigmentation in patients with stable disease. Furthermore, keratinocytes contribute to the autoimmune insult in vitiligo. Keratinocytes express MHC II in perilesional skin and may present melanosomal antigens in the context of MHC class II after the pigmented organelles have been transferred from melanocytes. Moreover, keratinocytes secrete cytokines and chemokines including CXCL-9, CXCL-10, and IL-15 that amplify the inflammatory circuit within vitiligo skin and recruit melanocyte-specific, skin-resident memory T cells. In summary, keratinocytes can influence vitiligo development by a combination of failing to produce survival factors, limiting melanocyte adhesion in lesional skin, presenting melanocyte antigens and enhancing the recruitment of pathogenic T cells.

Enhancement of antiproliferative potential of metformin against melanoma mice B16 cells using an optimized liposomal drug delivery system.

OBJECTIVE: Metformin-loaded liposomes were optimized for enhanced antiproliferative activity against melanoma. METHODS: Box-Behnken design and response surface methodology were employed to optimize entrapment efficiency, ex-vivo permeation and vesicle size. The optimized formulation was prepared by both the lipid hydration method and the modified injection method for comparison. Different concentrations of Pluronic F127 were employed for modification. Selected Pluronic-modified formulation (lipid molar concentration 55 mmol, cholesterol 30% and drug loading 52.9 mg) was characterized for morphology, entrapment efficiency, permeation and vesicle size. RESULTS: The optimized formulation resulted in entrapment efficiency of 41.7 ± 0.01%, vesicle size of 1.405 ± 0.061 µm and percentage of permeation was 67 ± 5.5%. The improved cytotoxic effect of the selected formulation against melanoma mice B16 cell line compared with metformin solution was determined using MTT assay. Compared with the corresponding drug solution, the Pluronic-modified optimized liposomes displayed a highly efficient cytotoxic effect as evidenced by significant lowering in IC50 -887.3 ± 23.2 and 26.71 ± 0.69 µg/ml, respectively, P < 0.0001. CONCLUSION: This study introduces an optimized liposomal formulation with enhanced cytotoxic effect against melanoma B16 cell line.

The use of intralesional corticosteroid combined with narrowband ultraviolet B in vitiligo treatment: clinical, histopathologic, and histometric evaluation.

BACKGROUND: Treatment of vitiligo with intralesional steroid (ILS) injections has shown to be successful in quite a few studies. It is a simple and safe treatment when used with caution with a better response in localized lesions. OBJECTIVES: The aim of the present study is to explore the efficacy and safety of using different concentrations of intralesional corticosteroid combined with NB-UVB phototherapy in the treatment of non-segmental vitiligo (NSV) patients. METHODOLOGY: Twenty patients with non-segmental vitiligo were subjected to different concentrations of ILS injections (triamcinolone acetonide); that was carried out monthly for six sessions. All patients were also subjected to twice-weekly sessions of NB-UVB for 6 months. Punch biopsy was taken from each patch before and at the end of treatment sessions. Each biopsy was stained with hematoxylin and eosin (H&E), Orcein, and Masson's trichrome stains. RESULTS: There was a significant difference between all groups in their repigmentation response (P = 0.017). After treatment, the epidermal thickness (histometry) was decreased (epidermal atrophy), especially with concentrations of 2.5 and 5 mg/ml of intralesional triamcinolone acetonide injection with decreased and disorganized collagen fibers. CONCLUSION: Intralesional corticosteroid injections combined with NB-UVB showed a good and well-tolerated therapeutic option for vitiligo. The concentrations of 0.625 and 1.25 mg/ml of triamcinolone acetonide were the safest with fewer side effects and complications. However, higher concentrations of 2.5 and 5 mg/ml were more effective but with more side effects.

Quercetin loaded cosm-nutraceutical electrospun composite nanofibers for acne alleviation: Preparation, characterization and experimental clinical appraisal.

In the cosmeceutical field, it is essential to develop topical delivery systems which would allow drugs to create a depot and permeate within the skin. The aim of the present study was to develop composite nanofibers of polyvinyl alcohol/quercetin/essential oils using the electrospinning technique, and assess their efficiency in acne alleviation. Quercetin was chosen due to its anti-inflammatory, anti-oxidant, and antibacterial activities. Nanofibers were characterized for their morphology, ex-vivo deposition/permeation, physical/mechanical integrity, thermal properties, and chemical characteristics. In addition, the anti-bacterial efficacy was tested on Propionibacterium acne (P. acne), and a cytotoxicity assay was carried out. Lastly, an experimental clinical trial was conducted on acne patients, where the percentage reduction of inflammatory, non-inflammatory and total acne lesions was taken as evaluation criterion. Results showed that quercetin was successfully loaded into the nanofibers which were homogenously dispersed. They showed a reasonable skin deposition percentage of 28.24% ± 0.012, a significantly higher antibacterial efficacy against Propionibacterium acne than quercetin alone, and were utterly safe on skin fibroblastic cells. Upon clinical examination on acne patients, the nanofibers showed 61.2%, 14.7%, and 52.9% reduction of inflammatory, comedonal, and total acne lesions respectively, suggesting a promising topical anti-acne delivery system.

Coenzyme Q10 phospholipidic vesicular formulations for treatment of androgenic alopecia: ex vivo permeation and clinical appraisal.

INTRODUCTION: Coenzyme Q10 (CoQ10) is an antioxidant molecule with anti-aging activity on human hair, and because of its pharmaceutical limitations such as large molecular weight, high lipophilicity and poor water solubility, its therapeutic effectiveness has been hampered. Therefore, different vesicular nanocarriers were developed in the current work, for enhancement of the skin penetration of CoQ10 for treatment of androgenic alopecia. AREAS COVERED: In order to overcome the poor skin penetration of CoQ10, it was formulated in liposomes, transfersomes, ethosomes, cerosomes and transethosomes using the thin-film hydration method. Results revealed that transethosomes were the carrier of choice for CoQ10, in which it displayed a particle size of 146 nm, zeta potential -55 mV and entrapment efficiency of 97.63%. Transethosomes also achieved the highest deposition percentage for CoQ10, exceeding 95% in the different skin layers. Upon clinical examination in patients suffering from androgenic alopecia, CoQ10 transethosomes displayed better clinical response than the administration of CoQ10 solution, which was further confirmed by dermoscopic examination. EXPERT OPINION: Findings of this study further prove that loading antioxidants such as CoQ10 in nanocarriers maximizes their therapeutic efficiency, and opens many opportunities for their application in treatment of several other topical diseases.

The impact of active vitamin D administration on the clinical outcomes of acne vulgaris.

Acne vulgaris is one of the most common chronic inflammatory skin disorder affecting millions of people worldwide. Vitamin D deficiency has a role in various inflammatory skin diseases as acne. This study aimed to investigate the serum level of 25 hydroxy vitamin D in acne patients and to assess the efficacy and safety of active vitamin D in management of acne. This study was conducted on 100 patients with acne and 100 healthy controls, then the 100 acne patients were randomized to either the study group that received 0.25ug alfacalcidol daily or the placebo group that received oral placebo during the 3 months study period. Serum levels of 25-hydroxy-vitamin D were significantly lower in acne patients than in healthy control and were inversely correlated to the severity of acne. After alfacalcidol administration, the study group showed significant higher level of 25(OH) D levels (p < .05) compared to placebo group. In addition, median serum level of IL6 and TNFα significantly decreased (p < .05) in the study group in comparison to placebo group and as compared to their baseline results. Acne patients are more commonly to have vitamin D deficiency as compared to healthy people and hence, alfacalcidol might have a beneficial role in the acne management with no reported side effects.

Chitosan nanoparticles making their way to clinical practice: A feasibility study on their topical use for acne treatment.

Despite the popularity of chitosan as a biodegradable polymer used in a variety of applications, clinical trials involving chitosan or its nanoparticles are still scarce. Moreover, the use of nutraceuticals as a replacement to conventional chemical treatments has become currently popular, and if combined with nanotechnology, nutraceuticals can achieve a comparable or even better therapeutic outcome. In the current work, chitosan nanoparticles loading the nutraceutical nicotinamide were optimized, characterized, and clinically tested on patients suffering from acne vulgaris. The topical merits of chitosan nanoparticles were proven, in which they exhibited strong skin adhesion ex vivo and high nicotinamide deposition in the different skin layers (stratum corneum, epidermis and dermis) amounting to a total of 68%. When clinically tested on patients, nicotinamide nanoparticles displayed 73% reduction in the inflammatory acne lesions compared to untreated areas, hence proving that chitosan nanoparticles can be a clinically sounding option for treatment of skin diseases.

Cosm-nutraceutical nanovesicles for acne treatment: Physicochemical characterization and exploratory clinical experimentation.

The full exploration of the 'nutraceuticals' therapeutic potential in cosmetics has been hindered by their poor stratum corneum permeation. Therefore, the aim of the present study was to formulate a nutraceutical; quercetin, in novel vitamin C based nanovesicles (aspasomes), and to explore their beneficial effects in the treatment of acne. Aspasomes were characterized for their particle size, zeta potential, entrapment efficiency (EE%), 3-months storage stability, skin deposition/permeation, antioxidant potential, and morphology. Aspasomes antibacterial efficacy on Propionibacterium acnes using the zone of inhibition assay was also tested, whilst their safety on skin fibroblastic cells was assessed in vitro using 3T3 CCL92 cell lines. An exploratory clinical trial was conducted in acne patients, and the percentage reduction of inflammatory, non-inflammatory and total acne lesions was taken as the evaluation criterion. Results revealed that quercetin-loaded aspasomes displayed a desirable nanometer size (125-184 nm), negative charge with good storage stability, and high skin deposition reaching 40%. Aspasomes managed to preserve the antioxidant activity of quercetin, and exhibited a significantly higher antibacterial effect (15 ± 1.53 mm) against Propionibacterium acnes than quercetin alone (8.25 ± 2.08 mm), and were safe on skin fibroblastic cells. Upon clinical examination in 20 acne patients (14 females, 6 males), quercetin aspasomes exhibited reduction percentages of 77.9%, 11.8% and 55.3% for inflammatory lesions, comedones and total lesions respectively. This opens vast applications of the presented formulation in the treatment of other oxidative skin diseases, and delineates the nutraceuticals and nanoformulations prepared from natural materials as promising dermatological treatment modes.

Novel nicotinamide skin-adhesive hot melt extrudates for treatment of acne.

OBJECTIVES: Hot melt extrusion is a continuous process with wide industrial applicability. Till current date, there have been no reports on the formulation of extrudates for topical treatment of dermatological diseases. METHODS: The aim of the present work was to prepare and characterize medicated hot melt extrudates based on Soluplus polymer and nicotinamide, and to explore their applicability in acne treatment. The extrudates were characterized using DSC, FTIR, XRD, and DVS. The extrudates were also tested for their skin adhesion potential, ability to deposit nicotinamide in different skin layers, and their clinical efficacy in acne patients. RESULTS: The 10% nicotinamide extrudates exhibited amorphous nature which was reserved during storage, with no chemical interaction between nicotinamide and Soluplus. Upon contrasting the skin adhesion and drug deposition of extrudates and nicotinamide gel, it was evident that the extrudates displayed significantly higher adhesion and drug deposition reaching 4.8 folds, 5.3 folds, and 4.3 folds more in the stratum corneum, epidermis and dermis, respectively. Furthermore, the extrudates significantly reduced the total number of acne lesions in patients by 61.3% compared to 42.14% with the nicotinamide gel. CONCLUSION: Soluplus extrudates are promising topical drug delivery means for the treatment of dermatological diseases.

Evaluation of intralesional injection of bleomycin in the treatment of plantar warts: clinical and dermoscopic evaluation.

BACKGROUND: Treatment of plantar warts is difficult and requires multiple treatments, and they are more refractory to treatment than common warts. Intralesional bleomycin has been used in the treatment of warts with varying degrees of success. AIM: The aim of the present work is to evaluate the efficacy of intralesional injection of bleomycin in the treatment of plantar warts based on clinical and dermoscopic observations. PATIENTS AND METHODS: Bleomycin (1 mg/ml) was injected intralesionally into the pared plantar wart every 2 weeks for a maximum of four sessions. Patients were followed both clinically and by the use of dermoscope. RESULTS: The cure rate of plantar warts treated with bleomycin was 69.3% with minimal and tolerable side effects. CONCLUSION: Intralesional injection of bleomycin is an effective and safe treatment of plantar warts. Dermoscope is recommended in the evaluation of treatment success, as it can accurately tell if the wart needs further treatment, preventing premature stoppage of the treatment, thus decreasing the possibility of recurrences.