Rx -to- OTC switch increased access and lowered cost of topical adapalene.

Topical adapalene gel is an effective and well tolerated acne treatment that transitioned from prescription to over-the-counter (OTC) availability in 2016. Historically, prescription to OTC transitions have lowered costs to patients and payers and increased access to medications. This study used sales and prescriber data to assess access to topical retinoid therapies and their costs in the pre- and post- Rx-to-OTC transition. We demonstrate that the prescription to OTC transition of adapalene gel increased access to this medication, while lowering costs to patients and payers, including Medicare patients. These results provide a necessary call to action for future OTC shifts with other high safety profile, well-tolerated medications in ultimate efforts and hopes of cost savings for patients, insurers, and Medicare within our healthcare industry.

2% supramolecular salicylic acid hydrogel vs. adapaline gel in mild to moderate acne vulgaris treatment: A multicenter, randomized, evaluator-blind, parallel-controlled trial.

OBJECTIVE: Salicylic acid (SA) has been used for treatment of acne of different severity levels. However, there are few researches about the safety and efficacy for treatment of mild to moderate acne, and the improvement of the skin condition by using 2% supramolecular salicylic acid (SSA) compared to Davuwen Adapaline gel. METHODS: A multicenter, randomized, assessor-blind and parallel-controlled study was conducted. A total of 500 patients (trial group: 249, control group: 251) with mild to moderate (grade I-II) facial acne vulgaris were recruited in this study over a 16-week trial period. Patients in the trial group were treated with Broda 2% SSA hydrogel, while control group treated with Davuwen Adapaline gel once a day. The number of inflammatory papules, comedones, and pustules were counted and the rate of lesion reduction was calculated pre- and post-treatment. Then, the skin physiological indicators, including L*a*b*, TEWL, skin sebum and hydration were measured. Statistical analysis was conducted using SAS 9.4. Significance was set at p = 0.05. RESULTS: At the end of 12 weeks' therapy, the regression and markedly improvement rate of the trail group and the control group were 51.01% and 43.10% respectively, and there was no significant difference in the improvement rate between two groups (p = 0.0831). Although, there was no difference in adverse events rate between two groups, the adverse events rate of the trail group was 0.40%, a little lower than the control group (0.80%). Moreover, there was a significant difference in the numbers of pores at T1 between two groups. CONCLUSION: Both 2% SSA and Adapaline gel were equally effective in the treatment of mild to moderate acne vulgaris. 2% SSA is worth the clinical promotion and application in mild to moderate acne vulgaris.

Efficacy of ceramides and niacinamide-containing moisturizer versus hydrophilic cream in combination with topical anti-acne treatment in mild to moderate acne vulgaris: A split face, double-blinded, randomized controlled trial.

INTRODUCTION: Topical therapy is the mainstay treatment of acne, and topical retinoids such as tretinoin, tazarotene, and adapalene are recommended as the first-line therapy for mild to moderate acne. However, the cutaneous irritations may occur, and the dermocosmetics are recommended to prevent side effects of anti-acne drugs and adhere to treatment. Thus, this study aims to compare the efficacy and tolerability of ceramides and niacinamide-containing moisturizer (CCM) versus hydrophilic cream in combination with topical anti-acne treatment in mild to moderate acne vulgaris. METHODS: This was an 8-week, randomized, double-blinded, split face study in 40 patients assigned for topical anti-acne medications (5% benzoyl peroxide and 0.1% adapalene gel), then randomly applied CCM or hydrophilic cream. All patients were followed at week 0, 2, 4, and 8 for acne improvement, adverse reactions, biometric, and biophysical evaluation. RESULTS: CCM could significantly improve the non-inflammatory, inflammatory, and total acne lesions compared with hydrophilic cream after week 8 of treatment. Interestingly, there was an improvement of global worst score, hemoglobin index, melanin index, TEWL, skin hydration, sebum production, and skin surface pH, with no statistically significant differences between the two treatments. No serious side effects from clinical application of CCM and hydrophilic cream in mild to moderate acne vulgaris patients. CONCLUSION: Ceramide and niacinamide-containing moisturizer in combination with anti-acne medication can significantly improve acne lesions and decrease cutaneous irritations toward a satisfactory treatment outcome of mild to moderate acne vulgaris.

Adapalene induces adipose browning through the RARß-p38 MAPK-ATF2 pathway.

Adipose browning has recently been reported to be a novel therapeutic strategy for obesity. Because the retinoic acid receptor (RAR) is a potential target involved in browning, adapalene (AD), an anti-acne agent with RAR agonism, was examined in detail for its effects on adipose browning and the underlying mechanisms in vitro and in vivo. AD upregulated the expression of adipose browning-related markers in a concentration-dependent manner, promoted mitochondrial biogenesis, increased oxygen consumption rates, and lowered lipid droplet sizes in differentiated 3T3/L1 white adipocytes. Among the three retinoic acid receptors (RARα, RARß, and RARγ), knockdown of the gene encoding RARß mitigated AD-induced adipose browning. Similarly, LE135 (a selective RARß antagonist) attenuated AD action, suggesting that AD promotes adipose browning through RARß. Sequential phosphorylation of p38 mitogen-activated protein kinase (MAPK) and activating transcription factor 2 (ATF2) was critical for AD-induced adipose browning, based on the observations that either SB203580 (a p38 MAPK inhibitor) or ATF2 siRNA reduced the effects of AD. In vivo browning effects of AD were confirmed in C57BL/6J mice and high-fat diet-induced obese (DIO) mice after oral administration of AD either acutely or chronically. This study identifies new actions of AD as an adipose browning agent and demonstrates that RARß activation followed by increased phosphorylation of p38 MAPK and ATF2 appears to be a key mechanism of AD action.

Efficacy and Safety of a Fixed-Dose Clindamycin Phosphate 1.2%, Benzoyl Peroxide 3.1%, and Adapalene 0.15% Gel for Moderate-to-Severe Acne: A Randomized Phase II Study of the First Triple-Combination Drug.

BACKGROUND: A three-pronged approach to acne treatment-combining an antibiotic, antibacterial, and retinoid-could provide greater efficacy and tolerability than single or dyad treatments, while potentially improving patient compliance and reducing antibiotic resistance. OBJECTIVES: We aimed to evaluate the efficacy and safety of triple-combination, fixed-dose topical clindamycin phosphate 1.2%/benzoyl peroxide (BPO) 3.1%/adapalene 0.15% (IDP-126) gel for the treatment of acne. METHODS: In a phase II, double-blind, multicenter, randomized, 12-week study, eligible participants aged ≥ 9 years with moderate-to-severe acne were equally randomized to once-daily IDP-126, vehicle, or one of three component dyad gels: BPO/adapalene; clindamycin phosphate/BPO; or clindamycin phosphate/adapalene. Coprimary endpoints were treatment success at week 12 (participants achieving a ≥ 2-grade reduction from baseline in Evaluator's Global Severity Score and clear/almost clear skin) and least-squares mean absolute changes from baseline in inflammatory and noninflammatory lesion counts to week 12. Treatment-emergent adverse events and cutaneous safety/tolerability were also assessed. RESULTS: A total of 741 participants were enrolled. At week 12, 52.5% of participants achieved treatment success with IDP-126 vs vehicle (8.1%) and dyads (range 27.8-30.5%; P ≤ 0.001, all). IDP-126 also provided significantly greater absolute reductions in inflammatory (29.9) and noninflammatory (35.5) lesions compared with vehicle or dyads (range inflammatory, 19.6-26.8; noninflammatory, 21.8-30.0; P < 0.05, all), corresponding to > 70% reductions with IDP-126. IDP-126 was well tolerated, with most treatment-emergent adverse events of mild-to-moderate severity. CONCLUSIONS: Once-daily treatment with the novel fixed-dose triple-combination clindamycin phosphate 1.2%/BPO 3.1%/adapalene 0.15% gel demonstrated superior efficacy to vehicle and all three dyad component gels, and was well tolerated over 12 weeks in pediatric, adolescent, and adult participants with moderate-to-severe acne. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03170388 (registered 31 May, 2017).

Development and Evaluation of Topical Delivery of Microemulsions Containing Adapalene (MEs-Ap) for Acne.

The main objective of the study was to prepare the microemulsions containing adapalene (MEs-Ap) to enhance epidermal penetration, dermal retention, and local bioavailability compared with the commercial preparation. The optimal formulations were selected by solubility experiments, pseudo-ternary phase diagram, and percutaneous permeation experiments and the physiochemical properties were also investigated. Then, the study of permeability, retention, safety, pharmacodynamics, and pharmacokinetics in the skin for MEs-Ap compared with the commercial preparation were researched. The optimized formulation was developed as follows: the ratio of AP, isopropyl myristate, polyoxyethylene hydrogenated castor oil, ethanol, and water was 0.01:1:1.25:3.75:4 (w/w). The globule size and average viscosity of the optimized MEs-Ap were 99.34 nm and 1.7 mPa·s, respectively, which was oil-in-water microemulsion without serious irritation or allergy for skin. The Js, Qn, and Qretention of MEs-Ap (0.81 ± 0.19 µg/cm2/h, 24.73 ± 4.24 µg/cm2, 2.08 ± 0.18 µg/cm2) were apparently higher than Differin® (0.022 ± 0.009 µg/cm2/h, 0.536 ± 0.103 µg/cm2, and 0.523 ± 0.130 µg/cm2) respectively. The local bioavailability study showed that the AUC0 → 36h of the MEs-Ap in the dermal (19.6 ± 1.22 µg/cm2) was significantly improved comparing to Differin® (13.9 ± 1.73 µg/cm2) (p < 0.01). The pharmacodynamics study showed that the therapeutic effect of MEs-Ap was better than that of Differin® in the acne model of rabbit auricle. These results suggested that the MEs-Ap could be considered as a having higher epidermal penetrability, dermal retention, local bioavailability, efficacy, and safety topical preparations for acne. Graphical abstract.

Application of ultrasound-mediated adapalene-coated lysozyme-shelled microbubbles in UVA-induced skin photoaging.

Photoaging, the premature aging of skin induced by ultraviolet rays, is characterized by wrinkling, roughness, laxity, and pigmentary changes. Various natural and synthetic retinoids have been explored for the treatment of aging. Among retinoids, adapalene (Ada, 0.3%) is one of the most potent and widely used drugs to treat photoaging. However, it causes irritant reactions that limit its acceptance by patients. Several studies have shown the applicability of Lysozyme (Lys)-shelled microbubbles (MBs) for drug delivery through sonophoresis, and recently we have shown its efficiency to treat inflammatory skin disease. Here, we report the construction of novel Ada-LysMBs based on opposite electric charges for combined effects to treat photoaging. The Ada-LysMBs were self-assembled and had a mean diameter of 2857 nm. The maximum loading efficiency of Ada onto LysMBs was 13.99 ± 0.59%. An acoustic power density of 3 W/cm2 for 1 min revealing maximum penetration depth of LysMBs was optimized for further in vitro and in vivo studies of Ada-LysMBs. It was observed that in vitro Ada release from Ada-LysMBs at 6 h after ultrasound (US) treatment was more rapid at pH 7.4 (82%) than at pH 5.5 (73%). Franz diffusion experiments on isolated porcine skin indicated that US approximately doubled Ada delivery by Ada-LysMBs and Ada + LysMBs at 12 h and six-fold Lys permeation by LysMBs at 6 h, compared to these treatments alone. A 5-week in vivo study in mice identified significant wrinkle reduction in animals treated with US plus Ada-LysMBs. Our findings indicate that US may be used with Ada-LysMBs in the water phase to treat photoaging by normalizing hyperkeratinization and promoting collagen synthesis.

First reported cases of actinic folliculitis treated successfully with topical retinoid.

Actinic folliculitis (AF) is a rare recurrent seasonal photodermatosis, relatively newly characterized by nonpruritic, monomorphic pustules and papules appearing 4-24 h after exposure to sunlight. Lesions usually affect the face but also appear on the upper chest and arms. Resolution normally occurs within 7-10 days with cessation of sunlight exposure. AF is resistant to standard treatments used for acne vulgaris and acne rosacea, with only oral retinoids previously being reported as effective. We report the first two cases, to our knowledge, of AF responding extremely effectively to a topical retinoid.

Development and Investigation of Vitamin C-Enriched Adapalene-Loaded Transfersome Gel: a Collegial Approach for the Treatment of Acne Vulgaris.

Adapalene-loaded transfersome gel containing vitamin C as a combination therapy for the management of acne vulgaris was developed in the present study. The transfersome was prepared by reverse-phase evaporation, and the effect of various process parameters were investigated by the Design of Experiment (DOE) approach and optimized based on the particle size (PS), polydispersity index (PDI), zeta potential (ZP), and entrapment efficiency (EE). The selected tranfersomes were further evaluated for their thermal behavior and morphology by transmission electron microscopy and turbidity measurements and incorporated into a gel with/without vitamin C. The gel was evaluated and compared with the marketed product (Adiff gel) for various physicochemical parameters, and in vivo studies in testosterone-induced rat models of acne. The prepared transfersomes had PS in the range of 280 to 400 nm, PDI values of 0.416 to 0.8, ZP of - 38 to - 20 mV, and % EE of 32 to 70%. DSC studies confirmed a positive interaction of the components in the transfersome. Surface morphology confirmed that the vesicles were spherical, unilamellar, and discrete. A relative deformability study showed higher elasticity of the transfersomes compared with Adiff aqs gel. Ascorbyl-6-palmitate in adapalene-loaded transfersome gel containing vitamin C (ADVTG) was found to have a good antioxidant free radical-scavenging activity. An in vitro drug release study showed that the sustained release of the transfersomal formulations was attributed to the flexibility of the vesicles by which penetration was increased. ADVTG was found to be promising in treating acne compared with the marketed product. Graphical Abstract.

CD271 promotes STZ-induced diabetic wound healing and regulates epidermal stem cell survival in the presence of the pTrkA receptor.

Diabetes mellitus (DM) often causes delayed wound healing in patients, which can lead to limb loss, disability, and even death. Many conventional therapeutic strategies have been proposed, but there is still no effective therapy for DM wounds. This study aimed to explore the effects of CD271 and phosphorylated tyrosine kinase receptor A (pTrkA) on the migration and proliferation abilities of epidermal stem cells (eSCs) and on the activation of DM wound healing. We investigated the interventional effects of CD271-overexpressing eSC (CD271 eSC) treatment and pTrkA inhibition (through k252a treatment) on delayed wound healing using mice with streptozotocin-induced DM. The migration and proliferation abilities of control eSCs, CD271 eSCs, and k252a-treated CD271 eSCs were observed under high-glucose conditions. Decreases in CD271 and increases in pTrkA were observed in DM mouse skin compared with control mouse skin; in addition, the rate of wound closure in DM mice was promoted by CD271 eSC treatment but delayed by pTrkA inhibition. Furthermore, the CD271 eSC migration and proliferation were greater than of control eSCs. Compared with that of CD271 eSCs, the number of CD271+k252a eSCs decreased significantly under high-glucose conditions. In parallel, the expression levels of the pERK, pAkt, and pJNK pathways increased in CD271 eSCs and decreased in CD271+k252a eSCs under high glucose. Our findings demonstrate that CD271 and pTrkA affect DM wound closure by promoting the eSC migration and proliferation. This mechanism involving the pERK, pAkt, and pJNK pathways might be a new therapeutic target for the treatment of delayed wound re-epithelialization in DM.

Will the polyphenol and adapalene combination be a good strategy on acne vulgaris?

Acne vulgaris is a common disease which affects about 85% of the population. Various topical drugs are available, but the retinoid derivatives are mostly taken into consideration. They are used as a first-line treatment drugs. However, they also have few side effects. Whereas, adapalene which is a third generation topical retinoid has fewer side effects compared to other derivatives. In this, we hypothesize that the combination therapy of adapalene and flavonoid could improve the efficacy and thereby it can also decrease the treatment time. Since, flavonoids possess multiple activities we assume that it can improve the action of the drug by showing a synergistic activity. Moreover, when we incorporate these two drugs in nanoemulgel, it can easily penetrate into the skin and produce its therapeutic action. Hence, we assume that if this hypothesis proves to be correct then this method will be an effective one in treating acne (pustule).

Adapalene-loaded poly(ε-caprolactone) microparticles: Physicochemical characterization and in vitro penetration by photoacoustic spectroscopy.

Adapalene (ADAP) is an important drug widely used in the topical treatment of acne. It is a third-generation retinoid and provides keratolytic, anti-inflammatory, and antiseborrhoic action. However, some topical adverse effects such as erythema, dryness, and scaling have been reported with its commercial formula. In this sense, the microencapsulation of this drug using polyesters can circumvent its topical side effects and can lead to the enhancement of drug delivery into sebaceous glands. The goal of this work was to obtain ADAP-loaded poly(ε-caprolactone) (PCL) microparticles prepared by a simple emulsion/solvent evaporation method. Formulations containing 10 and 20% of ADAP were successfully obtained and characterized by morphological, spectroscopic, and thermal studies. Microparticles presented encapsulation efficiency of ADAP above 98% and showed a smooth surface and spherical shape. Fourier transform infrared spectroscopy (FTIR) results presented no drug-polymer chemical bond, and a differential scanning calorimetry (DSC) technique showed a partial amorphization of the drug. ADAP permeation in the Strat-M membrane for transdermal diffusion testing was evaluated by photoacoustic spectroscopy (PAS) in the spectral region between 225 and 400 nm after 15 min and 3 h from the application of ADAP-loaded PCL formulations. PAS was successfully used for investigating the penetration of polymeric microparticles. In addition, microencapsulation decreased the in vitro transmembrane diffusion of ADAP.

Comparison of efficacy of aminolaevulinic acid photodynamic therapy vs. adapalene gel plus oral doxycycline for treatment of moderate acne vulgaris-A simple, blind, randomized, and controlled trial.

BACKGROUND: Although progress has been made in the study of photodynamic therapy for acne, studies using current recommended therapies as active comparators are lacking. METHODS: Randomized, controlled trial involving 46 patients with moderate inflammatory facial acne, 23 patients received two sessions of PDT separated by 2 weeks (ALA 20% incubated 1.5 hours before red light irradiation with 37 J/cm2 fluence) and 23 patients received doxycycline 100 mg/d plus adapalene gel 0.1%. In both groups, from the sixth week, we started adapalene gel 0.1% as maintenance therapy until 12 weeks of follow-up. Primary end point was the reduction of acne lesions at the 6-week follow-up, which was evaluated by 2 investigators blinded to the intervention. RESULTS: The median percent reductions in noninflammatory lesion count (P = 0.013) and total lesions (P = 0.038) at 6 weeks was found to be significantly higher in the group receiving PDT. At 12 weeks there was a greater reduction of inflammatory lesions in PDT group with 84% vs. 74% for group who received doxycycline plus adapalene (P = 0.020) as well as in reducing total lesions with 79% vs. 67% respectively (P = 0.026). No severe side-effects were observed for either therapy. CONCLUSIONS: ALA-PDT offers promise as an alternative treatment for moderately severe inflammatory acne that has a higher effectiveness than the combination of doxycycline and adapalene gel in reducing noninflammatory and total lesions at 6 weeks. There were significantly superior reductions at 12 weeks in the combination of PDT group followed by adapalene gel in total, inflammatory, and noninflammatory lesions.

Differin® and depilation, a word of warning.

BACKGROUND: Retinoid products are becoming increasingly popular due to their efficacy and mild side effect profile. A few cases of epidermal stripping with wax depilation have been reported, but all have been associated with oral retinoid use. AIMS: We aim to increase awareness of this adverse effect. METHODS: N/A Results: N/A Conclusion: While retinoid products are effective and have a low side effect profile, they may still cause adverse effects including the possibility of epidermal stripping with wax depilation.

Comparable efficacy of adapalene 0.3% gel and tretinoin 0.05% cream as treatment for cutaneous photoaging.

BACKGROUND: Adapalene has been previously evaluated as a treatment for actinic keratosis (AK) and solar lentigines and shown to improve signs of photoaging. OBJECTIVES: To evaluate whether adapalene 0.3% gel is non-inferior to tretinoin 0.05% cream as treatment for photoaged skin. MATERIALS & METHODS: An investigator-blinded, parallel-group comparison study was conducted in Brazil. Subjects were randomised in a 1:1 ratio to receive, once daily, adapalene 0.3% gel or tretinoin 0.05% cream. Subjects were evaluated at Weeks 1, 4, 8, 12, 16, 20 and 24, based on clinical signs of cutaneous photoaging, histopathological and digital morphometric findings, as well as safety and tolerability. RESULTS: A comparison of clinical efficacy showed that both treatments did not differ significantly regarding clinical evaluation of the following criteria: global cutaneous photoaging, periorbital wrinkles, ephelides/melanosis, forehead wrinkles, and AK. CONCLUSION: Adapalene 0.3% gel showed non-inferior efficacy to tretinoin 0.05% cream as treatment for photoaged skin, with a similar safety profile. Adapalene 0.3% gel may therefore be considered a safe and effective option for the treatment of mild or moderate photoaging.

Codelivery of benzoyl peroxide & adapalene using modified liposomal gel for improved acne therapy.

AIM: Current study investigates therapeutic efficacy and tolerability of benzoyl peroxide (BPO)- and adapalene (AD)-loaded modified liposomal gel (BPO-AD-mLipo gel) for improved acne therapy. MATERIALS & METHOD: BPO-AD-mLipo were optimized and loaded in Carbopol gel. Both BPO-AD-mLipo and BPO-AD-mLipo-gel were extensively characterized for different quality attributes. Ex vivo dermal bioavailability, dermal distribution, in vivo anti-acne efficacy and skin irritation studies were performed and compared with marketed formulation (Epiduo®, Galderma Laboratories LP, TX, USA). RESULTS: BPO-AD-mLipo illustrated size 256.4 ± 9.3 nm with polydispersity index âˆ¼ 0.2. Significantly enhanced dermal bioavailability (AD-2.1, 5.4; BPO-3.0, 7.83-fold) and reduction in skin irritation and papule density in animal model were observed with BPO-AD-mLipo-gel as compared with free drugs and Epiduo, respectively. CONCLUSION: BPO-AD-mLipo gel provides effective and safer alternative approach for codelivery of anti-acne drugs.

Delivery of adapalene using a novel topical gel based on tea tree oil nano-emulsion: Permeation, antibacterial and safety assessments.

The aim of present study was to design and optimize 0.1% adapalene loaded nano-emulsion to improve the drug efficacy and increase its user compliance. Effect of type and concentration of surfactants was studied on size of 0.1% adapalene loaded nano-emulsion. Optimized formulation was then evaluated for particle size, polydispersity index, morphology, viscosity, and pH. Subsequently, 1% carbopol® 934 was incorporated to the optimized formulation for preparation of its gel form. The efficacy and safety of 0.1% adapalene loaded nano-emulsion gel was assessed compared to marketed gel containing 0.1% adapalene. In-vitro studies showed that adapalene permeation through the skin was negligible in both adapalene loaded nano-emulsion gel and adapalene marketed gel. Furthermore, drug distribution studies in skin indicated higher retention of adapalene in the dermis in adapalene loaded nano-emulsion gel compared with adapalene marketed gel. Antibacterial activity against Propionibacterium acnes showed that adapalene loaded nano-emulsion is effective in reducing minimum inhibitory concentration of the formulation in comparison with tea tree oil nano-emulsion, and pure tea tree oil. In vivo skin irritation studies showed absence of irritancy for adapalene loaded nano-emulsion gel. Also, blood and liver absorption of the drug, histological analysis of liver and liver enzyme activity of rats after 90 days' treatment were investigated. No drug was detected in blood/liver which in addition to an absence of any adverse effect on liver and enzymes showed the potential of adapalene loaded nano-emulsion gel as a novel carrier for topical delivery of adapalene.

Efficacy and Safety of Adapalene 0.3%/Benzoyl Peroxide 2.5% Gel Plus Oral Doxycycline in Subjects With Severe Inflammatory Acne Who Are Candidates for Oral Isotretinoin.

INTRODUCTION: Acne treatment guidelines suggest a combination approach with topical therapy including a topical retinoid, benzoyl peroxide and an oral antibiotic, or oral isotretinoin (OI), as first-line treatment options for severe acne vulgaris (AV). This study evaluated the efficacy and safety of a daily regimen of 0.3% adapalene and 2.5% benzoyl peroxide (0.3% A/BPO) gel and oral doxycycline 100 mg twice daily in severe (nonnodulocystic, non-conglobate) inflammatory AV. METHODS: This was a phase 4, 12-week, single-arm, openlabel, multi-center investigational study. Subjects (males and females, 12 or older, with severe inflammatory AV, Investigator Global Assessment [IGA] 4, and less than equal to 4 nodulocystic lesions, n=186) were considered OI candidates at baseline by the investigator. OI candidacy was re-evaluated at each study visit. Efficacy endpoints included inflammatory lesion (IL) reduction (week 12), IGA success (defined as IGA 0 [Clear] or 1 [Almost Clear], weeks 4, 8, and 12), percent reduction in lesions (weeks 4, 8, and 12), and subject questionnaires (week 12). Safety assessments included adverse events (AEs) and tolerability. RESULTS: Mean IL counts were significantly reduced from baseline to the end of the study (mean [SD]; baseline, 44.8 (21.73); week 12, 14.8 (16.11); mean percent reduction, 66.2% [30.47]; P less than .0001). By week 12, 37.1% of subjects achieved IGA Success (n=69, P less than .0001). Most subjects self-reported at least moderate improvement in AV (90.2%), and were "Satisfied" or "Very Satisfied" with the study treatment overall (83.2%). 41.9% of the subjects were no longer considered by their investigator to be OI candidates at week 4. At 12 weeks, only 19.9% were still considered OI candidates. CONCLUSION: 0.3% A/BPO + DOX is an effective and safe treatment option for severe inflammatory AV, before starting OI treatment, or as an alternative when OI cannot be used. ClinicalTrials.gov identifier: NCT02899000

J Drugs Dermatol. 2018;17(3):264-273.

Selective delivery of adapalene to the human hair follicle under finite dose conditions using polymeric micelle nanocarriers.

Drug delivery systems that target the pilosebaceous unit (PSU) selectively could improve the clinical management of diseases that originate in the hair follicle. The aims of this study were (i) to prepare polymeric micelles using d-α-tocopheryl polyethylene glycol succinate diblock copolymer that incorporated adapalene (ADA), a retinoid indicated for Acne vulgaris, and (ii) to investigate the feasibility of delivering ADA preferentially to the PSU under finite dose conditions - thereby better approximating actual conditions of use by patients. Incorporation of ADA into spherical micelles (dn <20 nm) increased aqueous solubility by ∼50 000-fold (from <4 ng mL-1 to 0.2 mg mL-1). Optimized micelle solution and gel formulations (0.02% ADA) were stable after storage for 4 weeks at 4 °C. Finite dose experiments using full-thickness porcine and human skin revealed that ADA delivery efficiency from micelle solution and gel formulations was equivalent and was >2- and 10-fold higher than that from Differin® gel and Differin® cream (products containing ADA at 0.1% (w/w)). Follicular delivery studies in human skin, using a punch biopsy technique to extract the intact PSU, demonstrated that the micelle solution and gel formulations did indeed enable preferential delivery of ADA to the PSU (4.5- and 3.3-fold higher, respectively, than that to PSU-free skin biopsies). Confocal laser scanning microscopy provided visual corroboration that ADA was uniformly distributed in the hair follicles. In conclusion, the results confirmed that polymeric micelle nanocarriers enabled selective, targeted drug delivery to the PSU under finite dose conditions and so might improve therapy of follicular diseases and decrease off-site side-effects.