Dermocosmetics: beneficial adjuncts in the treatment of acne vulgaris.

Introduction: Dermocosmetics are increasingly being recognized as an integral part of acne management. Dermocosmetics may minimize the side effects of acne medications, provide synergistic effects by improving the efficacy of other treatments, and limit exposure to environmental factors such as ultraviolet radiation. We aimed to provide an overview of the active ingredients and different types of preparations used in dermocosmetics for acne, and highlight supporting evidence for their use in clinical practice.Methods: A literature search for selected key words was performed using PubMed. Additional papers were identified based on author expertize.Results and discussion: The different types of active ingredients in dermocosmetics for acne can be classified as: sebum-controlling, antimicrobial, anti-inflammatory, anti-oxidant and/or keratolytic. Such agents may modulate the pathogenic pathways in acne. Dermocosmetics can be formulated as emulsions/creams, cleansers or camouflaging make-up. Dermocosmetics are useful treatment adjuncts for acne and have been shown to improve the clinical signs of acne, reduce transepidermal water loss and modify sebum production. Dermocosmetics have also been associated with reducing side effects of pharmacological treatments, high levels of patient satisfaction and increased adherence to treatment regimens. Together this evidence supports the use of dermocosmetics in clinical practice.

Novel Polymeric Lotion Formulation of Once-Daily Tazarotene (0.045%) for Moderate-to-Severe Acne: Pooled Phase 3 Analysis.

Background: As current tazarotene formulations indicated for acne (0.1%) can cause irritation, a new tazarotene 0.045% lotion formu-lation was developed using polymeric emulsion technology. The objective was to assess efficacy, safety, and tolerability of tazarotene 0.045% lotion in patients with moderate-to-severe acne in a pooled analysis of data from two identical phase 3, double-blind, random-ized, vehicle-controlled 12-week clinical studies. Methods: Patients aged ≥9 years with moderate-to-severe acne were randomized (1:1) to tazarotene 0.045% lotion or vehicle lotion applied once daily. Inflammatory and noninflammatory lesion counts and Evaluator's Global Severity Score (EGSS) were assessed. Treatment success was defined as a ≥2-grade improvement in EGSS and a score of 'clear'/'almost clear'. Adverse events (AEs) and cutaneous safety and tolerability were also assessed. Results: In total, 1614 patients (mean age: 20.5 years) were randomized to tazarotene 0.045% lotion (n=799) or vehicle (n=815). At week 12, tazarotene 0.045% lotion demonstrated statistically significant superiority versus vehicle in reducing inflammatory and non-inflammatory lesion counts (least-squares mean percent changes from baseline: inflammatory, -57.9% vs -47.8% [P<0.001]; noninflam-matory, -56.0% vs -42.0% [P<0.001]). Treatment success at week 12 was also greater with tazarotene 0.045% lotion versus vehicle (30.4% vs 17.9%; P<0.001). The most frequent treatment-emergent AEs related to tazarotene treatment were application site pain (5.3%), dryness (3.6%), and exfoliation (2.1%). Conclusions: The new tazarotene 0.045% lotion formulated with polymeric emulsion technology demonstrated statistically signifi-cantly superior efficacy versus vehicle and was well tolerated in pediatric and adult patients with moderate-to-severe acne in this pooled analysis of 2 vehicle-controlled phase 3 studies. J Drugs Dermatol. 2020;19(3):272-279. doi:10.36849/JDD.2020.4869.

The molecular structure, spectroscopic features and electronic properties of tioxolone under the external electric field.

It is very helpful to understand the properties of molecules by studying a series of physical and chemical changes in molecules under an external electric field (EEF). Tioxolone is an important bioactive compound for its wide applications in the medical field. In this work, density function theory calculations combined with EEF were used to investigate the structure, spectra and electronic properties of tioxolone. The calculated results indicate that the bond lengths, bond angles, total energy, dipole moment, charge and aromaticity of tioxolone change under EEF. As EEF increases, the energy gap of tioxolone gradually reduces and makes it easier to participate in chemical reactions. Under the effect of EEF, the infrared and UV-Vis spectra show vibrational stark effect, which causes a redshift or blueshift of the frequency. These results help to understand the effect of EEF on structures and electronic properties for tioxolone, which will further provide effective guidance for the various application of tioxolone.

Exploring the potential of minoxidil tretinoin liposomal based hydrogel for topical delivery in the treatment of androgenic alopecia.

Purpose: Androgenic alopecia (AGA) is a condition of progressive hair loss and involves follicular miniaturization triggered mainly due to varying levels of androgen besides environmental and genetic factors, which may also play some role. Minoxidil (MXD) has been considered as most effective therapeutic moiety to treat this disorder. Another drug Tretinoin (TRET) is known for its comedolytic activity and is reported to enhance percutaneous absorption of MXD. Presently both these drugs are being utilized for treatment of androgenic alopecia (AGA) in solution form which poses several problems in terms of poor solubility of drug, frequency of application and side effects.Materials and methods: Current work investigates liposomal hydrogel system for simultaneous delivery of MXD and TRET to overcome the limitations of existing formulation. Successful development of liposomes was commenced by thin film hydration method and various parameters affecting desired characteristics like size, morphology, entrapment efficiency; stability and ex vivo permeation were optimized. The formulated liposomes were further characterized for various physicochemical properties and evaluated for in vivo irritancy study in animals.Results and discussion: Results suggested prepared liposomes to be stable, homogenous and capable to hold both the drugs within. Association with hydrogel enhanced the permeation of MXD through skin ex vivo but TRET retained on the skin. Liposome loaded hydrogel was found to be non-irritant to skin.Conclusion: Overall developed system showed potential for effective and simultaneous delivery of both the drugs.

Effect of Metamorphed Keratolytic Agent on the Behavior of Imiquimod Loaded Hybrid Vesicles Containing Gel.

The cost, side effects, and patient compliance-related issues of topically effective imiquimod have prevented its widespread acceptance. The present work intends to evaluate the feasibility of overcoming the shortcomings of poorly soluble and skin-penetrating immunomodulator by using biocompatible keratolytic agent with drug-loaded hybrid vesicles. Salicylic acid was complexed with phospholipid through simple mixing and incorporated into carbopol 940 gel containing drug-loaded vesicles, prepared by thin-film hydration method. The morphology, physicochemical properties, rheological behavior, release profile, and dermatokinetics of developed gel were compared with control gel (developed gel without keratolytic agent). In ex vivo drug release studies across the rat skin, there was significant increase in the steady-state permeation flux (Jss) and skin retention of drug from developed gel in comparison with control. There was favorable change in almost every evaluated dermatokinetic parameter. The innocuous nature of control gel had not changed on addition of skin structure-altering agent. The developed gel was found to be stable at room temperature and humidity for 1 year.

Novel Tretinoin 0.05% Lotion for the Once-daily Treatment of Moderate-to-Severe Acne Vulgaris in an Adult and Adolescent Female Population

Background: Acne vulgaris (acne) is a common dermatological condition typically associated with adolescents, affecting about 85% of young people. However, it is also prevalent and persistent into adulthood, particularly in females. The efficacy of tretinoin in acne is well documented with large pivotal studies. The first lotion formulation of tretinoin was developed to provide an important alternative option to treat acne patients who may be sensitive to the irritant effects of other tretinoin formulations. Objective: To determine whether efficacy and safety of tretinoin 0.05% lotion was similar in adolescent (<18 years) and adult (>=18 years) women with moderate-to-severe acne. Methods: Post hoc analysis of two multicenter, randomized, double-blind, vehicle-controlled Phase 3 studies in moderate or severe acne. Female subjects (aged 9 to 58 years, N=909) randomized (1:1) to receive tretinoin 0.05% lotion or vehicle, once-daily for 12 weeks. Efficacy assessments included changes in baseline inflammatory and noninflammatory lesions and treatment success (at least 2-grade reduction in Evaluator's Global Severity Score [EGSS] and clear/almost clear). Safety, adverse events (AEs), and cutaneous tolerability were evaluated throughout. Results: At week 12, mean percent reduction in inflammatory and noninflammatory lesion counts in female subjects were 56.9% and 51.7%, respectively, compared with 47.1% and 34.9% with vehicle (P=<0.001). Similar results were seen in adult and adolescent females in terms of reduction in inflammatory lesion counts with tretinoin 0.05% lotion; reduction in noninflammatory lesions was significantly greater in adult females (P=0.002). Treatment success was achieved by 23.6% of female subjects by week 12, compared with 13.5% on vehicle (P<0.001). Although treatment success was somewhat greater in adult females (24.6% versus 21.6%), the difference was not significant. The majority of AEs were mild and transient. There were five serious AEs (SAEs) reported (4/1, adult/adolescent, respectively). The most frequently reported treatment related AEs with tretinoin 0.05% lotion were application site pain (3.0%/5.7%), and application site dryness (4.9%/6.4%). Local cutaneous safety and tolerability assessments were generally mild-to-moderate and improved by week 12. Slight increases in mean scores were observed for scaling, burning and stinging within the first four weeks and appeared to be transient. Conclusions: Tretinoin 0.05% lotion was significantly more effective than its vehicle in achieving treatment success and reducing inflammatory and noninflammatory lesions in female acne. Noninflammatory lesion count reduction was significantly greater in adult females compared with adolescent females. The new lotion formulation was well-tolerated. J Drugs Dermatol. 2019;18(2):178-188.

Cohort Using a Ceramides Containing Cleanser and Cream With Salicylic Acid for Dry, Flaking, and Scaling Skin Conditions

Introduction: The skin of subjects with dry, flaking, and/or scaling conditions is characterized by decreased water and skin lipids content among other findings. It is well understood that daily use of gentle cleansers and moisturizers may help to restore and maintain an optimal skin barrier function. A cohort study of patients with dry skin was developed to evaluate efficacy of daily use of a ceramide containing cleanser and cream that also has salicylic acid. Methods: Thirty-five adults with mild-to-moderate dry skin conditions were recruited from four dermatology centers in Canada. With consent, the subjects received twice daily treatment with the ceramides containing cleanser and cream that also has salicylic acid. Physician and subject assessed skin condition comparing baseline versus (day 0) versus day 28 (end) was scored using the Dry skin classification scale and the Global Aesthetic Improvement Scale (GAIS). Subjects also rated satisfaction, product features, quality of life aspects, safety, and tolerability. Results: Thirty-four subjects completed the treatment and study period; one was lost to follow up. Daily use of the evaluated cleanser and moisturizer significantly improved skin condition when comparing day 0 versus day 28 (+/- 5 days (end)) results. Both the physicians and subjects using the dry skin classification scale and GAIS scored a significant improvement of the dry skin condition. After treatment subjects reported a significant improvement in the quality of their professional life, self-image, and social life. The products were shown to be safe, comfortable, and well tolerated. Conclusion: The results indicated the cleanser and moisturizer to offer an effective, easy and comfortable option for dry skin conditions. J Drugs Dermatol. 2019;18(1):80-85.

Lanolin-based organogel of salicylic acid: evidences of better dermatokinetic profile in imiquimod-induced keratolytic therapy in BALB/c mice model.

The primary aim of the present study was to develop lanolin-based organogel with enhanced delivery potential and reduced skin irritation for the treatment of hyperkeratotic lesions and scaling. The drug was encapsulated in the lipidic bilayers of organogel. The values of particle size, polydispersity index (PDI), and zeta potential of the developed carrier system was found to be 257.5 nm, 0.272, and -24.9 mV, respectively. The system was pseudoplastic in nature with the yield value of 2.3078 Pa. The skin permeation studies exhibited superiority of the prepared lanolin-based organogel formulation over the conventional gel formulation (CGF). Further, the dermatokinetic studies also confirmed better permeation and enhanced skin bioavailability of SA to epidermis as well as dermis vis-à-vis the CGF. In conclusion, the developed organogel system not only improved the delivery profile of SA but also reduced the skin irritant potential. The current findings can provide a suitable alternative for the development of an effective topical formulation of SA for the treatment of hyperkeratotic lesions.

The essential oil from Citrus limetta Risso peels alleviates skin inflammation: In-vitro and in-vivo study.

ETHNOPHARMACOLOGICAL RELEVANCE: Citrus fruit peels are traditionally used in folk medicine for the treatment of skin disorders but it lacks proper pharmacological intervention. Citrus limetta Risso (Rutaceae) is an important commercial fruit crops used by juice processing industries in all continents. Ethnopharmacological validation of an essential oil isolated from its peels may play a key role in converting the fruit waste materials into therapeutic value added products. AIM OF THE STUDY: To evaluate the chemical and pharmacological (in-vitro and in-vivo) profile of essential oil isolated from Citrus limetta peels (Clp-EO) against skin inflammation for its ethnopharmacological validation. MATERIALS AND METHODS: Hydro-distilled essential oil extracted from Citrus limetta peels (Clp-EO) was subjected to gas chromatography (GC) analysis for identification of essential oil constituents and its anti-inflammatory evaluation through in vitro and in vivo models. RESULTS: Chemical fingerprint of Clp-EO revealed the presence of monoterpene hydrocarbon and limonene is the major component. Pre-treatment of Clp-EO to the macrophages was able to inhibit the production of pro-inflammatory cytokines (TNF-α, IL-6, IL-1ß) in LPS-induced inflammation as well as the production of reactive oxygen species (ROS) in H2O2-induced oxidative stress. In in-vivo study, topical application of Clp-EO was also able to reduce the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ear thickness, ear weight, lipid peroxidation, pro-inflammatory cytokines production and ameliorate the histological damage in the ear tissue. In-vitro and in-vivo toxicity study indicate that it is safe for topical application on skin. CONCLUSION: These findings suggested the preventive potential of Clp-EO for the treatment of inflammation linked skin diseases.

Cantharidin in Dermatology.

Cantharidin is natural toxin produced by the blistering beetle. It has both vesicant and keratolytic features by inducing acanthloysis through targeting the desmosomal dense plaque, leading to detachment of the desmosomes from the tonofilaments. There are two available liquid preparations for dermatologic use, Canthacur (0.7% cantharidin) and Canthacur PS (1% cantharidin 30%/salicylic acid/2% podophylotoxin). The former preparation is indicated for the treatment of common warts, periungual warts, and molluscum contagiosum, while the more potent latter preparation is indicated only for plantar warts. Both preparations provide painless applications with outcomes similar to other treatment modalities for warts and molluscum contagiosum; however, neither is approved by the Food and Drug Administration (FDA). The lack of FDA approval could be related to its toxic effects following oral ingestion, which include ulceration of the gastrointestinal and genitourinary tracts, along with electrolyte and renal function disturbance in humans and animals. The mechanism of action, dermatologic indications, application techniques, and complications of cantharidin preparations are discussed.

Extemporaneous Compounding of Oral Acitretin Suspension for Pediatric Patient with Generalized Pustular Psoriasis.

Generalized pustular psoriasis is rare in children, but it can occur and affect an extensive body surface area of a child. Treatment regimens can include medications that are not available in pediatric dosage form. Acitretin is considered one of the treatment options for acute generalized pustular psoriasis in children, but, in Singapore, it is only available as Neotigason capsules. Extemporaneous compounding of the powder content in the capsules was developed for formulating the oral acitretin suspension with a standardized formulation table and compounding process at National Skin Centre. An appropriate beyond-use date of the extemporaneous preparation was assigned after reviewing the photostability data of acitretin, compatibility of the active ingredient and excipients, and United States Pharmacopeia <795> guidelines. It is deemed appropriate to assign a beyond-use date of 14 days when the extemporaneous preparation is stored in amber glass bottles at 2 degrees C to 8 degrees C.

Development of Smart Semisolid Formulations to Enhance Retinoic Acid Topical Application.

Retinoids play a very important role in the topical treatment of acne vulgaris. However, their use is restricted because of the limited photostability responsible for local adverse effects as erythema, dryness, itching, and stinging. In this way, the therapeutic efficacy of such molecules is strongly reduced, resulting, at the same time, harmful for the patient upon light exposure. Thus, a suitable technological strategy is necessary to increase retinoid stability in order to have a product both safe and efficacious. With this aim, new inorganic-organic hybrids based on tretinoin (retinoic acid, RET) and hydrotalcite-like compounds (HTlc) have been prepared and well characterized by X-ray powder diffraction, inductively coupled plasma spectrometry, thermal analyses, scanning electron microscopy, and UV-Vis spectrophotometric measurements. Such hybrids, namely, ZnAl-HTlc-RET and MgAl-HTlc-RET, were formulated as simple gels for topical use and submitted to further studies in order to evaluate their rheological properties, photostability, and RET release capability. The RET photostability resulted improved upon intercalation into HTlc, both in MgAl-HTlc and ZnAl-HTlc, as proved by the data acquired during irradiation of the sample at 366 nm. This strategy is suitable for the realization of safe, efficacious, and compliant topical formulations for acne treatment.

Correlation of hydrotropic solubilization by urea with logD of drug molecules and utilization of this effect for topical formulations.

Solubilization of drugs in aqueous phases of liquid and semisolid environment is typically achieved by co-solvents or surfactants. On contrast, solubilization by means of hydrotropic agents, i.e., small hydrophilic organic compounds like urea or citric acid, is little explored in the context of pharmaceutical formulations. Especially, with regard to topical dosage forms, however, hydrotropic solubilization can provide valuable alternatives to establish solubilization approaches. A difficulty of employing hydrotropic solubilization was that its extent could not be predicted for different drug molecules. Using a chemically heterogeneous set of 12 compounds relevant for dermatology (with overall 16 different logD values tested), we were able to demonstrate that hydrotropic effects of urea can be predicted by logD values of drugs. All compounds with logD values between 2 and 4.5 showed a solubility enhancement factor (EF) of >5 in 40% aqueous solutions of urea. For logD values below 2 or above 5, only EF<5 were found. For some compounds, e.g., diclofenac (pH 4) and prednicarbate could achieved only EF>5 at 5% urea and EF>250 at 20% urea.

Percutaneous absorption and antibacterial activities of lipid nanocarriers loaded with dual drugs for acne treatment.

The aim of this study was to develop lipid nanocarriers that combine tretinoin and tetracycline for the efficient topical delivery to treat acne vulgaris. Two different nanocarriers, nanoemulsions (NEs) and nanostructured lipid carriers (NLCs), were prepared, and we examined their average size, zeta potential, drug encapsulation percentage, and drug permeation via the skin. The antibacterial activities of the nanosystems against Staphylococcus aureus, Pseudomonas aeruginosa, and Propionibacterium acnes were evaluated by an agar diffusion assay and the amount of total protein. A ca. 200-nm particle size was achieved with the prepared nanoparticles. The size increased when incorporating a cationic surfactant. Dual-drug loading did not largely affect the size of negatively charged nanoparticles, but significantly reduced the particle size of positively charged nanocarriers. NEs and NLCs exhibited high entrapment of tretinoin which ranged 60-100%. Tetracycline mainly resided in the aqueous phase, with ca. 10% of molecules located at the particulate interface. An in vitro skin permeation study showed that NLCs enhanced tetracycline flux by about 2-times over the control solution. Tretinoin permeation was generally unaffected after nanoparticulate encapsulation. There was no significant difference in tretinoin delivery before or after tetracycline incorporation, while tetracycline permeation significantly decreased by 2-fold in the dual-drug system. Nanoparticulate loading mostly maintained the antibacterial activity of tetracycline. Negatively charged NEs and NLCs even strengthened the antibacterial ability against S. aureus compared to the control solution. This is the first report examining skin permeation and antibacterial activities of dual-drug nanocarriers for acne treatment.

Improved photostability and reduced skin permeation of tretinoin: development of a semisolid nanomedicine.

The aims of this work were to increase the photostability and to reduce the skin permeation of tretinoin through nanoencapsulation. Tretinoin is widely used in the topical treatment of various dermatological diseases such as acne, psoriasis, skin cancer, and photoaging. Tretinoin-loaded lipid-core polymeric nanocapsules were prepared by interfacial deposition of a preformed polymer. Carbopol hydrogels containing nanoencapsulated tretinoin presented a pH value of 6.08±0.14, a drug content of 0.52±0.01 mg g(-1), pseudoplastic rheological behavior, and higher spreadability than a marketed formulation. Hydrogels containing nanoencapsulated tretinoin demonstrated a lower photodegradation (24.17±3.49%) than the formulation containing the non-encapsulated drug (68.64±2.92%) after 8h of ultraviolet A irradiation. The half-life of the former was seven times higher than the latter. There was a decrease in the skin permeability coefficient of the drug by nanoencapsulation, independently of the dosage form. The liquid suspension and the semisolid form provided K(p)=0.31±0.15 and K(p)=0.33±0.01 cm s(-1), respectively (p≤0.05), while the samples containing non-encapsulated tretinoin showed K(p)=1.80±0.27 and K(p)=0.73±0.12 cm s(-1) for tretinoin solution and hydrogel, respectively. Lag time was increased two times by nanoencapsulation, meaning that the drug is retained for a longer time on the skin surface.

Uptake of pyrene in a breast-fed child of a mother treated with coal tar.

A woman was treated for atopic dermatitis with coal tar containing ointments. Coal tar containing ointments contain genotoxic polycyclic aromatic hydrocarbons. Over a period of 50 days the accumulated dose of different coal tar containing ointments treatments corresponded to 993 mg of pyrene and 464 mg of benz[a]pyrene. During this treatment she gave breast milk to her 3-month-old daughter. Analysis of urine samples from the breast-fed child showed elevated levels of urinary excretion of a metabolite of pyrene (1-hydroxypyrene, 1-OHP). These levels were in the same range as urinary excretion levels of this metabolite observed in the mother's urine. As no pyrene was observed in breast milk at a limit of determination of 0.0035 micromol/L, transfer of pyrene from mother to child via breast milk is not likely. Also, a low level of 1-hydroxypyrene observed in the mother's milk did not account for the observed urinary excretion levels in the child. It must therefore be assumed that pyrene was transferred from mother to child via another route, presumably direct skin-to-skin or skin-to-mouth contact. Dermatologists should inform their patients who receive treatment with coal tar containing ointments of the risk of transfer of polycyclic aromatic hydrocarbons by skin-to-skin or skin-to-mouth contact.

Retinoic acid effects on thyroid function of female rats.

AIMS: Retinoic acid is widely used in dermatological treatment and thyroid cancer management; however its possible side-effects on normal thyroid function remains unknown. We aimed to determine the effects of retinoic acid on thyroid function of adult female rats. MAIN METHODS: Female Wistar rats were treated with all-trans-retinoic acid and 13-cis retinoic acid for 14 and 28 days. Then, rats were killed and thyroid function was evaluated. KEY FINDINGS: Serum T4 and thyrotropin levels remained unchanged, while serum T3 increased in animals treated with all-trans-retinoic acid for 14 days. No changes were observed in hepatic or renal type 1 iodothyronine deiodinase (D1) activities, while thyroid D1 was higher in animals treated for 14 days with all-trans-retinoic acid, which could be related to the increased serum T3 levels. 13-cis retinoic acid increased thyroid iodide uptake after 28 days. These results show effects of retinoic acid treatment on these thyroid proteins: sodium/iodide symporter and deiodinase. SIGNIFICANCE: Retinoic acid is able to interfere with normal thyroid function, increasing thyroid type 1 deiodinase activity, serum T3 levels and sodium/iodide symporter function. However, the effects are time- and retinoic acid isomer-dependent. Since serum thyrotropin levels did not change in any group, the effects observed are probably mediated by a direct retinoic acid effect on the normal thyroid.