Adapalene 0.1% gel

Acne vulgaris is a common skin condition that significantly impacts both physical appearance and mental well-being. Acne, being a chronic skin condition, often requires continuous treatment. This study aims to evaluate the efficacy and safety of clindamycin phosphate 1.2%/benzoyl peroxide 3% compared to clindamycin phosphate 1.2%/adapalene 0.1% combinations for treating acne vulgaris. A systematic review and meta-analysis of randomized controlled trials were carried out following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, and three databases were searched to identify RCTs comparing CLIN/BPO with CLIN/ADAP. Primary outcomes included treatment-emergent adverse events, inflammatory and non-inflammatory lesion counts, and application site side effects. Statistical analyses were conducted using RevMan 5.3. The study included a total of 800 participants across three RCTs. The meta-analysis of three RCTs demonstrated a significantly lower risk of TEAEs with CLIN/BPO (OR = 0.49, 95% CI: 0.35-0.86, p < 0.001). CLIN/BPO also resulted in fewer application site side effects (OR = 0.33, 95% CI: 0.23-0.47, p < 0.001). However, no significant differences were observed between the groups for reducing inflammatory (MD = 1.34, 𝑝 = 0.121) or non-inflammatory lesion counts (MD = 0.04, 𝑝 = 0.98). The study concluded that although CLIN/BPO was associated with fewer side effects, both treatments were equally effective in reducing acne lesions. The favorable safety profile of CLIN/BPO, particularly regarding treatment-emergent and application-site adverse events, suggests it may be the more tolerable option for patients. Future studies with larger, more diverse populations are recommended to confirm these findings and explore long-term efficacy.

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BACKGROUND: Combination therapy is required for the treatment of moderate acne vulgaris. However, patient compliance in applying multiple topical formulations is poor. OBJECTIVE: To assess the efficacy and safety of a fixed-dose combination gel with adapalene 0.1% and clindamycin 1% (adapalene-clindamycin) relative to adapalene 0.1% monotherapy and clindamycin 1% monotherapy in patients with moderate facial acne vulgaris. METHODS: This was a randomized, controlled, assessor-blind, phase III study conducted in patients with moderate facial acne vulgaris. RESULTS: A total of 1617 patients were enrolled. At week 12, patients in the adapalene-clindamycin gel treatment group showed a significant reduction in the percentage change from baseline in total lesion count (- 66.85%), compared with adapalene alone (- 50.82%) or clindamycin gel alone (- 57.61%). The difference in the least square means of the adapalene-clindamycin gel group and adapalene group, or clindamycin gel group was - 16.08% (95% CI - 19.95% to - 12.21%) and - 9.38% (95% CI - 13.25% to - 5.51%;), respectively. At week 12, 19.28% of participants who received adapalene-clindamycin gel achieved at least 2-grade improvement in IGA, versus 7.74% with adapalene gel (OR 3.05, 95% CI 1.93, 4.80) and 14.77% with clindamycin gel (OR 1.42, 95% CI 0.97, 2.07). The study also achieved all its secondary endpoints. Adverse event rates were mostly mild to moderate and comparable across the three treatment groups. CONCLUSION: Adapalene 0.1%-clindamycin 1% combination gel is well tolerated and demonstrated superior efficacy over 0.1% adapalene gel monotherapy and 1% clindamycin gel monotherapy for the treatment of moderate acne vulgaris. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03615768.

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Abstract In our pursuit of enhancing acne treatment while minimizing side effects, we developed tailored Adapalene microsponges (MS) optimized using a Box–Behnken design 3 3 . The independent variables, Eudragit RS100 percentage in the polymer mixture, organic phase volume, and drug to polymer percentage, were explored. The optimized formulation exhibited remarkable characteristics, with a 98.3% ± 1.6 production yield, 97.3% ± 1.64 entrapment efficiency, and a particle size of 31.8 ± 1.1 µm. Notably, it achieved a 24 h cumulative drug release of 75.1% ± 1.4. To delve deeper into its efficacy, we evaluated the optimized microspongeal-gel in vitro, in vivo, and clinically. It demonstrated impressive retention in the pilosebaceous unit, a target for acne treatment. Comparative studies between our optimized Adapalene microspongeal gel and marketed Adapalene revealed superior performance. In vivo studies on Propionibacterium acnes-infected mice ears showed a remarkable 97% reduction in ear thickness, accompanied by a significant decrease in inflammatory signs and NF-κB levels, as confirmed by histopathological and histochemical examination. Moreover, in preliminary clinical evaluation, it demonstrated outstanding effectiveness in reducing comedonal lesions while causing fewer irritations. This not only indicates its potential for clinical application but also underscores its ability to enhance patient satisfaction, paving the way for future commercialization.

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INTRODUCTION: A three-pronged approach to acne treatment combining an antibiotic, antimicrobial, and retinoid may be more efficacious than single/double treatments while potentially reducing antibiotic resistance. This study evaluated the efficacy and safety of the first fixed-dose, triple-combination topical acne product, clindamycin 1.2%/adapalene 0.15%/benzoyl peroxide (BPO) 3.1% gel (CAB) using pooled phase 3 data. METHODS: In two identical phase 3 (N = 183; N = 180), double-blind, 12-week studies, participants aged ≥ 9 years with moderate-to-severe acne were randomized 2:1 to receive once-daily CAB or vehicle gel. Endpoints included ≥ 2-grade reduction from baseline in Evaluator's Global Severity Score and clear/almost clear skin (treatment success) and least-squares mean percent change from baseline in acne lesion counts. Treatment-emergent adverse events (TEAEs) and cutaneous safety/tolerability were evaluated. RESULTS: At week 12, 50.0% of participants achieved treatment success with CAB versus 22.6% with vehicle gel (P < 0.001). CAB resulted in > 70% reductions in inflammatory and noninflammatory lesions at week 12 (77.9% and 73.0%, respectively), which were significantly greater than vehicle (57.9% and 48.2%; P < 0.001, both). Most TEAEs were of mild-moderate severity, and < 3% of CAB-treated participants discontinued study/treatment because of AEs. Transient increases from baseline in scaling, erythema, itching, burning, and stinging were observed with CAB, but resolved back to or near baseline values by week 12. CONCLUSIONS: The innovative fixed-dose, triple-combination clindamycin phosphate 1.2%/adapalene 0.15%/BPO 3.1% gel was efficacious and well tolerated in children, adolescents, and adults with moderate-to-severe acne. Half of participants achieved clear/almost clear skin by 12 weeks, rates not previously seen in clinical studies of other topical acne products. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04214639 and NCT04214652.

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Acne vulgaris is a common chronic inflammatory skin disorder primarily caused by the overgrowth of Propionibacterium acnes (P. acnes). However, the therapeutic efficacy of traditional drugs is often limited due to their inability to penetrate the stratum corneum. Microneedles (MNs) are designed to penetrate the stratum corneum, enabling direct drug delivery to the epidermis. In this study, a new Dendrobium polysaccharide-based composite microneedle (DOP/CCF/PLGA@Adap-MN) delivery system was developed. Dendrobium polysaccharide (DOP) was utilized as the microneedle matrix, loaded with the Celosia cristata flavonoids (CCF) and poly(lactic-co-glycolic acid) adapalene nanoparticles (PLGA@Adap NPs). DOP not only enhanced the mechanical properties and transdermal efficiency of the microneedles but also provided intrinsic anti-inflammatory activity. CCF effectively inhibited the growth of P. acnes, while PLGA@Adap NPs slowly released adapalene to promote acne healing. In vivo studies using a P. acnes-induced mice model demonstrated that this microneedle system effectively reduced skin swelling, inhibited bacterial growth, and decreased inflammatory cell numbers in the skin. The use of bioactive DOP as a microneedle matrix, combined with sustained-release technology, provides a multifaceted and synergistic approach to acne treatment.

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Background/Objectives: Adapalene is a synthetic retinoid used as a treatment for acne vulgaris. In this study, we attempted to evaluate the dermal pharmacokinetics of adapalene utilizing experimental and in silico tools. Methods: We utilized three over the counter (OTC) adapalene gels to evaluate local dermal pharmacokinetics. A data-driven, robust, mechanistic dermal physiologically based pharmacokinetic (PBPK) model was developed by integrating the physicochemical properties of adapalene, the formulation attributes of the gels, and the biophysical aspects of dermal absorption. The dermal PBPK model was validated against experimental data using in vitro release studies and in vitro permeation studies with human cadaver skin. A clinical study was performed to evaluate the effects of adapalene from the three gel formulations. The impact of adapalene delivery from three gels on the stratum corneum (SC) thickness, pilosebaceous unit area, keratinocyte number, and epidermal thickness was captured using a non-invasive technique, line-field confocal optical coherence tomography (LC–OCT). These responses were evaluated using an Emax model. Results: The dermal PBPK model has successfully predicted adapalene penetration profiles across different gel formulations. The model accuracy, in predicting drug release and permeation characteristics, was confirmed using the experimental data. Clinical evaluation revealed formulation-dependent differences in adapalene’s effects on measured skin parameters, with distinct pharmacodynamic profiles observed for each gel formulation. Conclusions: The overall study gave us a detailed insight into potential effects of formulation on the dermal pharmacokinetics and pharmacodynamics of adapalene using three marketed gels.

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Aims: Multiple myeloma (MM) remains a challenging condition to cure, with persistent drug resistance negating the benefits of treatment advancements. The unraveling complexities in programmed cell death (PCD), inclusive of apoptosis, autophagy, and ferroptosis, have highlighted novel therapeutic avenues. Our study focuses on deciphering how adapalene (ADA), a small molecule compound, accelerates the demise of MM cells via targeting their compensatory survival mechanisms. Methods: To assess the impact of ADA on MM, we employed flow cytometry and trypan blue exclusion assays to determine cell viabilities across MM cell lines and primary patient samples post-treatment. To delineate ADA's therapeutic targets and mechanisms, we conducted RNA sequencing (RNA-seq), gene set enrichment analysis (GSEA), molecular docking, and molecular dynamics simulations. We further designed pre-clinical trials emphasizing MM, exploring the efficacy of ADA as a standalone and in combination with bortezomib (BTZ). Results: ADA elicited a dose-responsive induction of MM cell death. Building upon ADA's anti-MM capabilities as a single agent, we proposed that ADA-BTZ co-treatment might amplify this lethality. Indeed, ADA and BTZ together greatly potentiated MM cell death. ADA proved beneficial in restoring BTZ susceptibility in BTZ-resistant relapsed or refractory MM (RRMM) patient cells. Molecular simulations highlighted ADA's high affinity (-9.17 kcal/mol) for CD138, with MM-GBSA revealing a binding free energy of -27.39 kcal/mol. Detailed interaction analyses indicated hydrogen-bonding of ADA with CD138 at the Asp35 and Gln34 residues. Additionally, ADA emerged as a versatile instigator of both ferroptosis and apoptosis in MM cells. Furthermore, ADA disrupted activation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway triggered by BTZ, fostering cell death in BTZ-resistant MM subsets. Conclusion: ADA demonstrates a comprehensive capability to orchestrate MM cell death, exerting pronounced anti-MM activity while disrupting NF-κB-related drug resistance. ADA sensitization of MM cells to BTZ unravels its potential as a novel therapeutic drug for MM management.

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