Search Results (32)

Topical retinoids are the cornerstone of the treatment of multiple dermatological conditions. Long established in acne therapy, they exert effects on keratinization, inflammation, fibroblast activity, and collagen remodeling, suggesting a potential role in both the prevention and treatment of acne scars. This narrative review summarizes current evidence on the use of topical retinoids in acne vulgaris and acne scarring, focusing on different retinoid molecules, formulation technologies, and combination strategies. A review of published clinical and experimental studies evaluating tretinoin, adapalene, tazarotene, and trifarotene was performed, including their use as monotherapy and in combination with other topical agents or procedural interventions. The available data indicate that topical retinoids have a well-established position in acne treatment, can improve the appearance of atrophic acne scars, reduce the progression of scarring, and support skin remodeling. Advances in formulation technologies have improved tolerability, while combination approaches with agents such as benzoyl peroxide, antibiotics or procedural techniques have shown additive or synergistic effects, particularly in more severe cases. Nevertheless, much of the evidence regarding novel formulations is derived from small or heterogeneous study populations. In conclusion, topical retinoids represent a relevant therapeutic option in acne vulgaris and acne scarring, from monotherapy in mild cases to components of multimodal treatment protocols in more severe disease. Further large-scale, comparative studies are needed to better define the optimal clinical use of advanced drug delivery systems for topical retinoids. Full article

Stem cells, also known as progenitor cells, can differentiate into specialized cells for specific tissues. Genetic mutations and epigenetic changes may cause normal stem cells to become cancer-initiating cells. Research indicates that cells acquiring a mutation for myeloproliferative neoplasm (MPN) are likely to be long-term hematopoietic stem cells (LT-HSCs) at the top of the hematopoietic hierarchy. Natural killer (NK) cells play a crucial role in combating cancer by targeting and eliminating cancer stem cells (CSCs) while promoting their maturation. NK cells do this through direct lysis of CSCs or by releasing cytokines like interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α), which inhibit tumor growth and metastasis by driving differentiation of CSCs. Interleukin-2 (IL-2) enhances the activity of CD4+ and CD8+ T cells and boosts NK cell cytotoxicity. This study highlights a case of MPN with a more clinically aggressive Type 1 calreticulin (CALR) mutation, where a combination of low-dose IL-2 immunotherapy and targeted therapy with oral tretinoin (all-trans retinoic acid, ATRA, a vitamin A derivative) improved immune cells, particularly NK-cell-mediated destruction of malignant cells, reduced CALR mutation levels to undetectable, and alleviated disease symptoms. The aim is to offer a new, low-toxicity personalized treatment strategy that eradicates cancer-initiating stem cells, reduces side effects, and provides an option for patients with limited conventional therapy alternatives. Full article

Background/Objectives: Isotretinoin remains an essential therapy for severe acne, yet its safety profile continues to raise concerns. This study analyzed adverse event reporting patterns for isotretinoin versus topical retinoids using EudraVigilance data. Methods: Aggregated ADR data for isotretinoin and four topical retinoids (tretinoin, adapalene, tazarotene, trifarotene) were retrieved from the EMA ADRreports portal (April 2025). Disproportionality was assessed using reporting odds ratios (RORs) with 95% confidence intervals at the MedDRA system organ class (SOC) level. Significant demographic differences (age and sex; both p < 0.001) justified stratified ROR analyses for SOCs showing positive signals. Results: Among 35,030 isotretinoin and 3795 topical retinoid reports, isotretinoin showed strong over-reporting in six SOCs: psychiatric disorders (ROR 11.96; 95% CI 10.11–14.14), gastrointestinal disorders (3.88; 3.50–4.31), musculoskeletal and connective tissue disorders (2.89; 2.50–3.35), surgical and medical procedures, social circumstances, and ear and labyrinth disorders. Fourteen SOCs demonstrated significant under-reporting, including neoplasms, immune system disorders, cardiac disorders, and blood/lymphatic disorders. Stratified analyses confirmed the robustness of the positive signals. Psychiatric disorders exhibited the highest disproportionality in males (22.10; 16.11–30.31) and adolescents aged 12–17 (25.85; 13.32–50.19). Gastrointestinal and musculoskeletal signals remained significant across all age and sex strata. Conclusions: Isotretinoin presents a distinct safety profile characterized by consistently elevated reporting of psychiatric, gastrointestinal, and musculoskeletal adverse events, independent of age and sex. These results refine the comparative safety landscape of systemic versus topical retinoids and support focused pharmacovigilance monitoring. Full article

Background/Objectives: Acne is a common skin condition that is characterized by the manifestation of comedones, erythematous papules, pustules, and nodules over follicular areas. A huge contributing factor in the pathogenesis is colonization by Cutibacterium acnes (C. acnes) (formerly Propionibacterium acnes). Conventional treatments for acne range from topical to systemic agents with variable side effects and safety profiles. Adherence to prescribed treatments for acne is a huge challenge. Method: A quantitative cross-sectional study was conducted among 198 patients with dermatologist-confirmed acne vulgaris at King Abdulaziz University Hospital, Jeddah. Eligible participants had received topical and/or systemic treatment for at least one month. Exclusion criteria included other acne variants and inflammatory follicular disorders. Data on sociodemographics, medical and treatment history, and clinical characteristics were collected using a structured questionnaire. Treatment adherence was assessed with the validated ECOB scale. Associations between adherence and relevant variables were analyzed using Chi-squared and Mann–Whitney tests in SPSS v26, with significance set at p ≤ 0.05. Results: Non-adherence to anti-acne medications was 50.5% and was significantly associated with experiencing side effects, particularly skin dryness, and with moderate acne severity and topical treatment (p ≤ 0.05). No significant associations were found between adherence and demographic or medical history variables. Conclusions: Adherence to acne treatment remains a significant challenge for many patients. Improving patient education, addressing concerns about side effects, and providing practical support may help patients follow their prescribed therapies more consistently. Incorporating tools like the ECOB questionnaire into routine dermatology visits can support ongoing assessment and better management of treatment adherence. Full article

This article aims to point out new perspectives opened by genomics and epigenomics in skin rejuvenation strategies which target the main hallmarks of the ageing. In this respect, this article presents a concise overview on: the clinical relevance of the most important clocks and biomarkers used in skin anti-ageing strategy evaluation, the fundamentals, the main illustrating examples preclinically and clinically tested, the critical insights on knowledge gaps and future research perspectives concerning the most relevant skin anti-ageing and rejuvenation strategies based on novel epigenomic and genomic acquisitions. Thus the review dedicates distinct sections to: senolytics and senomorphics targeting senescent skin cells and their senescent-associated phenotype; strategies targeting genomic instability and telomere attrition by stimulation of the deoxyribonucleic acid (DNA) repair enzymes and proteins essential for telomeres’ recovery and stability; regenerative medicine based on mesenchymal stem cells or cell-free products in order to restore skin-resided stem cells; genetically and chemically induced skin epigenetic partial reprogramming by using transcription factors or epigenetic small molecule agents, respectively; small molecule modulators of DNA methylases, histone deacetylases, telomerases, DNA repair enzymes or of sirtuins; modulators of micro ribonucleic acid (miRNA) and long-non-coding ribonucleic acid (HOTAIR’s modulators) assisted or not by CRISPR-gene editing technology (CRISPR: Clustered Regularly Interspaced Short Palindromic Repeats); modulators of the most relevant altered nutrient-sensing pathways in skin ageing; as well as antioxidants and nanozymes to address mitochondrial dysfunctions and oxidative stress. In addition, some approaches targeting skin inflammageing, altered skin proteostasis, (macro)autophagy and intercellular connections, or skin microbiome, are very briefly discussed. The review also offers a comparative analysis among the newer genomic/epigenomic-based skin anti-ageing strategies vs. classical skin rejuvenation treatments from various perspectives: efficacy, safety, mechanism of action, evidence level in preclinical and clinical data and regulatory status, price range, current limitations. In these regards, a concise overview on senolytic/senomorphic agents, topical nutrigenomic pathways’ modulators and DNA repair enzymes, epigenetic small molecules agents, microRNAs and HOTAIRS’s modulators, is illustrated in comparison to classical approaches such as tretinoin and peptide-based cosmeceuticals, topical serum with growth factors, intense pulsed light, laser and microneedling combinations, chemical peels, botulinum toxin injections, dermal fillers. Finally, the review emphasizes the future research directions in order to accelerate the clinical translation of the (epi)genomic-advanced knowledge towards personalization of the skin anti-ageing strategies by integration of individual genomic and epigenomic profiles to customize/tailor skin rejuvenation therapies. Full article

Background/Objectives: With the rapid aging of the global population, the interest in therapies for age-related diseases has increased substantially. The skin is particularly important, as aging-related changes are visible and negatively impact quality of life. Therefore, the identification of senotherapeutic candidates that are effective against skin aging is of considerable importance. Given the cost and reproducibility limitations of existing senescence models, this study established three dermal fibroblast senescence models induced by etoposide, hydrogen peroxide, and ultraviolet A, representing intrinsic and extrinsic aging. Furthermore, considering the adverse effects of current photoaging treatments, such as tretinoin and methoxsalen, we investigated the senotherapeutic potential of araliadiol, a plant-derived compound, in these models. Methods: Senescence induction and validation were assessed using trypan blue-based cell counting, senescence-associated β-galactosidase (SA-β-gal) staining, and adenosine triphosphate content assays. The senotherapeutic potential of araliadiol was further evaluated using quantitative reverse transcriptase–polymerase chain reaction, Western blotting, immunofluorescence staining, and enzyme-linked immunosorbent assay. Results: Compared with non-senescent fibroblasts, senescent cells exhibited increased SA-β-gal positivity, elevated intracellular reactive oxygen species levels, and upregulated p16 and p21 expression. The senolytic agent ABT-737 selectively induced apoptosis in senescent fibroblasts but not in non-senescent fibroblasts, validating the models. Araliadiol showed no senolytic activity but demonstrated potential senomorphic effects, including reduced expression of senescence-associated secretory phenotype (SASP) genes (IL1β, IL6, IL8, CCL2, and CXCL1) and NF-κB p65 phosphorylation, suppression of MMP-1 (up to 2.35-fold reduction) and MMP-3 (up to 30.53-fold reduction) expression and AP-1 activation, and increased extracellular procollagen type I content (up to 18.35% increase). Conclusions: Araliadiol exerted senomorphic—but not senolytic—effects across three validated dermal fibroblast senescence models, supporting its potential as a natural topical therapeutic agent for mitigating skin aging. Full article

Topical tretinoin (all-trans-retinoic acid) is a first-generation vitamin A derivative with well-established efficacy in acne vulgaris and photoaging. Owing to its pleiotropic effects on epidermal differentiation, collagen synthesis, and skin pigmentation, numerous off-label uses have been proposed across dermatology. This narrative review summarizes current evidence on the efficacy and safety of topical tretinoin for multiple dermatological conditions, based on studies published between January 2000 and July 2025. Robust data from randomized clinical trials (RCTs) and systematic reviews support its benefit in acne and photoaging, whereas smaller RCTs and prospective studies indicate potential efficacy for melasma, postinflammatory hyperpigmentation, striae distensae, flat warts, alopecia areata, androgenetic alopecia, hypertrophic scars and keloids, and actinic keratosis and as pretreatment before chemical peels or laser resurfacing. However, high-quality, adequately powered trials with standardized outcome measures are still needed to establish clinical guidelines. Regarding cutaneous oncology, a large RCT demonstrated no preventive effect of tretinoin on keratinocyte carcinomas. Adverse events are typically mild, localized, and transient, and available evidence does not support an association with systemic adverse effects. Full article

The bleeding sap of Luffa cylindrica (L.) Roem has been used for the treatment of tuberculosis since the record of Supplements to Compendium of Materia Medica. The active components and possible mechanism of it are yet ambiguous. Hence, this study is focused on investigating the possible mechanism underpinning this effect on the perspective of the antioxidant ingredients from the bleeding sap. Through organic solvents extraction, HPLC fractionation, DPPH trials evaluation, and UHPLC-Orbitrap tandem MS identification, a total of 37 compounds were identified from the bleeding sap with the strongest antioxidant ability. Network pharmacology, bioinformatics, and molecular docking as well as literature review revealed 13 compounds, including linoleic acid, abietic acid, and tretinoin, that might exert their anti-tuberculosis function via actions with PPARγ or MAPK pathway. These findings offer guidance for the potential applications of Luffa cylindrica (L.) Roem as a functional food. Full article

Products with biologically active ingredients have emerged as a powerful category within the skincare and anti-aging sectors. Bridging the gap between pharmaceuticals and cosmetics, they offer therapeutic benefits supported by scientific evidence while maintaining the esthetic appeal of traditional skincare. This review aims to provide a comprehensive overview of cosmeceuticals with a particular focus on their anti-aging potential. This review highlights recent advances in cosmeceutical actives. Next-generation retinoids such as hydroxypinacolone retinoate and retinyl retinoate show comparable efficacy to tretinoin with improved tolerability, though current studies are small and short-term. Peptides, including signal, carrier, and neurotransmission-inhibiting peptides, offer multifunctional effects on extracellular matrix remodeling and wrinkle reduction, with supportive but modest clinical evidence enhanced by nanocarrier delivery. Antioxidants, particularly vitamin C and coenzyme Q10, are supported by controlled trials showing improvements in photoprotection, mitochondrial function, and wrinkle depth, though data are limited by sample size and follow-up. Botanical polyphenols are gaining prominence: nanoparticle-encapsulated epigallocatechin gallate (EGCG) enhances anti-photoaging activity in preclinical studies; oral microencapsulated curcumin has shown visible benefits in nutricosmetic trials; and bakuchiol, a retinol-like meroterpene, demonstrated comparable efficacy to retinol with superior tolerability. Advances in delivery systems—including nanoemulsions, phospholipid complexes, and encapsulation technologies—improve stability, bioavailability, and skin penetration. In conclusion, retinoids, vitamin C, and AHAs/BHAs remain the most evidence-based actives, whereas newer bioactives and advanced formulations appear promising but require larger, long-term randomized trials to establish their role in dermatologic practice. Full article

Background: The use of optical microscopic techniques has gained increasing attention in recent years for studying the bioavailability (BA) and bioequivalence (BE) of topical drugs. Stimulated Raman scattering (SRS), one type of optical imaging technique, probes chemical-specific information and has excellent spatiotemporal resolution. It uses intrinsic molecular vibrational signatures, and therefore, labeling samples or other treatments is unnecessary to track a molecule. Because of its unique advantages, studies have used SRS for BA evaluations and, more recently, for BE evaluations. In BE evaluation, low data variance within a treatment group is important to ensure sensitivity and specificity in comparing treatment groups. Methods: When measuring forward-direction SRS signals transmitted through skin, the signal intensity is susceptible to variance due to several factors, such as the microscope system’s performance, the different optical features of topical drug products, and the heterogeneity of skin in transmitting light. This work closely investigated the effects of these factors on an SRS signal and developed solutions to reduce their effects on the data variance. Specifically, we constructed a method using a dual-modality detector built in-house, which simultaneously measured both the SRS signal and total light transmission synchronized in time and co-registered in space. Results: We developed equations to normalize SRS signals using the transmission intensity, and the results demonstrated a clear improvement in the SRS signal via a reduction in the signal variance (up to a 9.46% CV value decrease) that is otherwise caused by various factors associated with the use of topical drugs and the composition of the skin. We carried out an exploratory BE study using tretinoin-containing topical products and observed improvements in BE assessment with the developed method (could achieve a reduction of 0.11 in the CI value). Conclusions: This work has led to a better understanding of the factors that affect SRS imaging and has provided an effective method to compensate for these factors in BE assessments. This is a critical initial effort for better practical implementation of SRS in cutaneous pharmacokinetics (cPKs) studies of topical drugs. Full article

In the preceding and early stages of cancer progression, local drug delivery to pre-cancerous and cancerous skin lesions may be applied as an alternative or supplementary therapy. At present, 5-Fluorouracil, imiquimod, and tirbanibulin creams and ointments have established their place in practice, while several other active pharmaceutical ingredients (APIs) (e.g., calcipotriol, tretinoin, diclofenac) have been repurposed, used off-label, or are currently being investigated in mono- or combined chemotherapies of skin cancers. Apart from them, dozens to hundreds of therapeutics of natural and synthetic origin are proven to possess anti-tumor activity against melanoma, squamous cell carcinoma (SCC), and other skin cancer types in in vitro studies. Their clinical introduction is most often limited by low skin permeability, challenged targeted drug delivery, insufficient chemical stability, non-selective cytotoxicity, or insufficient safety data. A variety of prodrug and nanotechnological approaches, including vesicular systems, micro- and nanoemulsions, solid lipid nanoparticles, nanostructured lipid carriers, polymeric nanoparticles, and others, offer versatile solutions for overcoming the biophysical barrier function of the skin and the undesirable physicochemical nature of some drug molecules. This review aims to present the most significant aspects and latest achievements on the subject. Full article

Psoriasis is an immune-related disorder that is marked by abnormal thickening of the skin, the rapid multiplication of keratinocytes, and complex interactions between immune cells and the affected areas. Although psoriasis cannot currently be cured, drugs can alleviate symptoms by regulating immune homeostasis and preventing comorbidities. There are many types of drugs to treat psoriasis: small-molecule drugs, including corticosteroids; retinoids; vitamin D analogs; and immunosuppressants, such as glucocorticoid ointment, tretinoin cream, methotrexate tablets, etc. Macromolecular biological drugs, such as Certolizumab, Secukinumab, Guselkumab, etc., include monoclonal antibodies that target various inflammatory signaling pathways. Compared with traditional small-molecule drugs, biological therapies offer better targeting and lower systemic side effects, but their high costs and invasive administration modes constrict their widespread use. Spesolimab is the latest biological agent used to target the interleukin-36 receptor (IL-36R) to be approved for market use, which significantly reduces the risk of general pustular psoriasis (GPP) flare by 84%. Additionally, there are several biological agents used to target the interleukin-23/T helper 17 cell pathway that have already entered Phase II and III clinical trials. At present, the first-line therapeutic strategy for mild psoriasis is topical administration. Systemic therapy and phototherapy are preferred for treating moderate to severe types. However, the current therapeutic drugs for psoriasis cannot completely meet the clinical needs. More advanced drug delivery systems with optimized target effects and better bioavailability are required. Nanocarriers are emerging for the delivery of proteins, nucleic acids, and cell-based therapies. In this review, we analyze the current status of psoriasis therapeutics and discuss novel delivery systems for diverse psoriasis drugs, as well as emerging cell-based therapies. We also summarize the therapeutic effectiveness of different delivery strategies. Full article

This study aims to build an optimal drug delivery system by manufacturing and evaluating a hydrogel contact lens using Tretinoin (ATRA) and protein nanoparticles to improve the drug delivery system as an ophthalmic medical contact lens. To evaluate the optical and physical properties of the manufactured lens, the spectral transmittance, refractive index, water content, contact angle, AFM, tensile strength, drug delivery, and antibacterial properties were analyzed. The contact lens was manufactured to contain ATRA and bovine serum albumin (BSA) in different ways, and the results confirmed that A, B, and C each had different physical properties. In particular, for Sample A, using the soak and release method and using ATRA solution in the contact lens with BSA added, the wettability was 55.94°, the tensile strength was 0.1491 kgf/mm², and drug delivery released 130.35 μm over 336 h, which was found to be superior to samples B and C. Therefore, the three hydrogel contact lenses compared in this study according to the addition method of ATRA and BSA can be used in various ways to build an optimal drug delivery system that is very useful as an ophthalmic medical lens. Full article

Background: Melasma is a challenging, acquired hyperpigmentary disorder. The gold standard treatment is Kligman’s formulation, which contains hydroquinone, tretinoin, and dexamethasone, but its long-term use is limited by the risk of exogenous ochronosis. Cysteamine, a tyrosinase inhibitor, reduces melanocyte activity and melanin production, showing strong depigmenting effects in patients resistant to Kligman’s formulation. Nonetheless, clinical studies have yielded inconsistent efficacy results. This meta-analysis aimed to assess the efficacy of cysteamine in treating melasma and to identify potential factors that may impact its therapeutic outcomes. Methods: A systematic search of PubMed, Embase, Web of Science, and CENTRAL, from the earliest record until August 2024, was conducted. Randomized controlled trials and quasi-randomized design studies related to topical cysteamine on melasma patients were included. The primary outcome was MASI or mMASI assessment after treatments. The current meta-analysis was conducted with a random-effects model. Subgroup analyses and meta-regressions were performed based on baseline MASI, disease duration of melasma, patient age, and sample size of the included studies. Funnel plots and Duval and Tweedie’s trim and fill method were adopted to assess the publication bias. Results: Eight studies were included for quantitative analysis. The analysis of MASI after topical cysteamine demonstrated a significant decrease compared to the placebo (p = 0.002). Compared to other melasma treatments, cysteamine did not show superior efficacy in mMASI (p = 0.277). The treatment efficacy of hydroquinone, modified Kligman’s formula, and tranexamic acid mesotherapy for melasma was not statistically different when compared to cysteamine (p = 0.434). Further analyses showed no benefit when allowing extended cysteamine application time (p < 0.0001). The meta-regression revealed the efficacy of cysteamine decreased as the duration of melasma increased (coefficient = 0.38, p = 0.0001, R² = 0.99). The funnel plot displayed some asymmetry. The trim and fill method suggested the adjusted effect size was 0.607 (95% CI = −0.720 to 1.935). Conclusions: Cysteamine exhibited efficacy in treating melasma patients; however, its depigmentation effect was comparable to hydroquinone-based regimens, tranexamic acid mesotherapy, and modified Kligman’s formula. Using cysteamine in patients with a short duration of melasma may result in better efficacy. Full article

Skin diseases are a common health problem affecting millions of people worldwide. Effective treatment often depends on the precise delivery of drugs to the affected areas. One promising approach is currently the transdermal drug delivery system (TDDS), whose significant challenge is the poor penetration of many compounds into the skin due to the stratum corneum (SC), which acts as a formidable barrier. To overcome this limitation, nanocarriers have emerged as a highly effective alternative. This review discusses the use of liposomes and ethosomes for transdermal drug delivery. Liposomes are micro- or nanostructures consisting of a lipid bilayer surrounding an aqueous core. They facilitate transdermal drug penetration and may be advantageous for site-specific targeting. Some methods of treating skin diseases involve incorporating drugs such as acyclovir, dithranol, and tretinoin or bioactive compounds such as fluconazole, melanin, glycolic acid, kojic acid, and CoQ10 into nanocarriers. The inability of liposomes to pass through the narrowed intercellular channels of the stratum corneum led to the invention of lipid-based vesicular systems such as ethosomes. They are structurally similar to conventional liposomes, as they are prepared from phospholipids, but they contain a high ethanol concentration. Ethosomes are noninvasive carriers that allow drugs to reach the deep layers of the skin. Examples of commonly used substances and drugs combined with ethosomes in cosmetics include methotrexate, ascorbic acid, vitamin A and E, and colchicine. A significant development in this area is the use of rutin-loaded ethosomes. Encapsulating rutin in ethosomes significantly improves its stability and enhances skin penetration, allowing more efficient delivery to deeper skin layers. In cosmetics, rutin–ethosome formulations are used to protect the skin from oxidative stress, reduce redness, and improve capillary strength, making it a valuable formulation in anti-aging and anti-inflammatory products. The results of the first clinical trial of the acyclovir–ethosome formulation confirm that ethosomes require further investigation. The work provides an update on recent advances in pharmaceutical and cosmetic applications, mentioning the essential points of commercially available formulations, clinical trials, and patents in the recent past. Full article