RETINOL

The skin is the most-extensive and -abundant tissue in the human body. Like many organs, as we age, human skin experiences gradual atrophy in both the epidermis and dermis. This can be primarily attributed to the diminishing population of epidermal stem cells and the reduction in collagen, which is the primary structural protein in the human body. The alterations occurring in the epidermis and dermis due to the aging process result in disruptions to the structure and functionality of the skin. This creates a microenvironment conducive to age-related skin conditions such as a compromised skin barrier, slowed wound healing, and the onset of skin cancer. This review emphasizes the recent molecular discoveries related to skin aging and evaluates preventive approaches, such as the use of topical retinoids. Topical retinoids have demonstrated promise in enhancing skin texture, diminishing fine lines, and augmenting the thickness of both the epidermal and dermal layers.

Bakuchiol is a phytochemical that has demonstrated cutaneous antiageing effects when applied topically. Early studies have suggested that bakuchiol is a functional analogue of topical retinoids, as both compounds have been shown to induce similar gene expression in the skin and lead to improvement of cutaneous photodamage. No in vivo studies have compared the two compounds for efficacy and side-effects. To compare the clinical efficacy and side-effect profiles of bakuchiol and retinol in improving common signs of cutaneous facial ageing. This was a randomized, double-blind, 12-week study in which 44 patients were asked to apply either bakuchiol 0·5% cream twice daily or retinol 0·5% cream daily. A facial photograph and analytical system was used to obtain and analyse high-resolution photographs of patients at 0, 4, 8 and 12 weeks. Patients also completed tolerability assessment questions to review side-effects. During study visits, a board-certified dermatologist, blinded to study group assignments, graded pigmentation and redness. Bakuchiol and retinol both significantly decreased wrinkle surface area and hyperpigmentation, with no statistical difference between the compounds. The retinol users reported more facial skin scaling and stinging. Our study demonstrates that bakuchiol is comparable with retinol in its ability to improve photoageing and is better tolerated than retinol. Bakuchiol is promising as a more tolerable alternative to retinol.

To evaluate the effectiveness of topical retinol (vitamin A) in improving the clinical signs of naturally aged skin. Randomized, double-blind, vehicle-controlled, left and right arm comparison study. Academic referral center. The study population comprised 36 elderly subjects (mean age, 87 years), residing in 2 senior citizen facilities. Topical 0.4% retinol lotion or its vehicle was applied at each visit by study personnel to either the right or the left arm, up to 3 times a week for 24 weeks. Clinical assessment using a semiquantitative scale (0, none; 9, most severe) and biochemical measurements from skin biopsy specimens obtained from treated areas. After 24 weeks, an intent-to-treat analysis using the last-observation-carried-forward method revealed that there were significant differences between retinol-treated and vehicle-treated skin for changes in fine wrinkling scores (-1.64 [95% CI, -2.06 to -1.22] vs -0.08 [95% CI, -0.17 to 0.01]; P<.001). As measured in a subgroup, retinol treatment significantly increased glycosaminoglycan expression (P = .02 [n = 6]) and procollagen I immunostaining (P = .049 [n = 4]) compared with vehicle. Topical retinol improves fine wrinkles associated with natural aging. Significant induction of glycosaminoglycan, which is known to retain substantial water, and increased collagen production are most likely responsible for wrinkle effacement. With greater skin matrix synthesis, retinol-treated aged skin is more likely to withstand skin injury and ulcer formation along with improved appearance.

The functionality and regenerative capacity of skin progressively deteriorate with aging. Topical use of peptides with a hyper-safety profile has been implicated in replacing retinol for skin anti-aging use, but is limited due to low stability and poor skin permeability. In this randomized, double-blinded, active- and vehicle-controlled clinical trial, we aim to evaluate the efficacy of an innovative cyclized hexapeptide-9 (CHP-9) with increased stability and skin permeability on skin aging compared to retinol. Healthy volunteers with aging skin were randomly assigned to twice-daily topical use of 0.002% CHP-9 serum, 0.002% retinol serum, or vehicle serum for 56 days. CHP-9 treatment significantly decreased the number, area, and roughness of both crow's feet (-2.20, 95% CI: -4.38, -0.03; -3.95, 95% CI: -5.80, -2.11; -1.95, 95% CI: -3.30, -0.59, respectively) and forehead wrinkles (-2.88, 95% CI: -4.21, -1.56; -4.90, 95% CI: -5.97, -3.82; -3.96, 95% CI: -5.92, -2.01, respectively), while retinol only decreased the area of crow's feet (-2.23, 95% CI: -3.86, -0.60) and the number and area of forehead wrinkles (-1.05, 95% CI:-1.69, -0.41). Except for the roughness of crow's feet, CHP-9 demonstrated significantly larger extent of effects than retinol did on all other outcomes. Furthermore, long-term use of CHP-9 showed time-dependent augmentation in its potency to reduce the number of crow's feet, and the number, area, and roughness of forehead wrinkles. In conclusion, CHP-9 is more potent than retinol in improving skin aging-related symptoms, especially for long-term use. Cyclization of collagen peptides may present a preventive/therapeutic option for skin aging.

Retinol, a derivative of vitamin A, is a ubiquitous compound used to treat acne, reduce wrinkles and protect against conditions like psoriasis and ichthyosis. While retinol is used as the primary active ingredient (AI) in many skin care formulations, its efficacy is often limited by an extreme sensitivity to degrade and toxicity at high concentrations. While microencapsulation is an appealing method to help overcome these issues, few microencapsulation strategies have made a major translational impact due to challenges with complexity, cost, limited protection of the AI and poor control of the release of the AI. We have developed a class of silicone particles that addresses these challenges for the encapsulation, protection and controlled release of retinol and other hydrophobic compounds. The particles are prepared by the sol-gel polymerization of silane monomers, which enables their rapid and facile synthesis at scale while maintaining a narrow size distribution (i.e., CV < 20%). We show that our particles can: (i) encapsulate retinol with high efficiency (>85%), (ii) protect retinol from degradation (yielding a half-life 9× greater than unencapsulated retinol) and (iii) slowly release retinol over several hours (at rates from 0.14 to 0.67 μg cm -2  s -1/2 ). To demonstrate that the controlled release of retinol from the particles can reduce irritation, we performed a double blind study on human subjects and found that formulations containing our particles were 12-23% less irritating than identical formulations containing Microsponge® particles (an industry standard by Amcol, Inc.). To show that the silicone particles can elicit a favorable biological response, similar to the Microsponge® particles, we applied both formulations to reconstructed human epidermal tissues and found an upregulation of keratin 19 (K19) and a downregulation of K10, indicating that the reduced irritation observed in the human study was not caused by reduced activity. We also found a decrease in the production of interleukin-1α (IL-1α) compared to formulations containing the Microsponge particles, suggesting lower irritation levels and supporting the findings from the human study. Finally, we show that the silicone particles can encapsulate other AIs, including betamethasone, N, N-diethyl-meta-toluamide (DEET), homosalate and ingenol mebutate, establishing these particles as a true platform technology.

Functional cosmetic materials with anti-aging properties, such as wrinkle reduction, often struggle to penetrate the skin's stratum corneum (skin barrier). Therefore, to exert anti-aging effects, these materials must pass through the skin barrier and reach fibroblasts in the dermal layer. In this study, deformable liposomes were developed for efficient transdermal delivery of retinol, a well-known anti-wrinkle agent. Five formulations (ML-1 to ML-5) were prepared using hydrogenated lecithin (HL) and mannosylerythritol lipid (MEL) as an edge activator with HL:MEL mass ratios of 10:0, 7:3, 5:5, 3:7, and 0:10. Their physicochemical properties, including particle size, zeta potential, polydispersity, encapsulation efficiency and deformability index were analyzed. For the optimal formulation, the liposome morphology was observed using cryo-TEM, and the retinol skin penetration ability of each liposome formulation was evaluated using a Franz diffusion cell. Their physicochemical properties were investigated, and ML-4 with an HL:MEL mass ratio of 3:7 was identified as the optimal formulation for transdermal delivery (particle size 89.3±6.8 nm, zeta potential -25.2±1.1 mV, polydispersity index 0.263±0.012, encapsulation efficiency 86.3±2.3%, and deformability index 5.76±1.9). Cryo-TEM analysis confirmed the liposomal morphology of ML-4. The retinol skin penetration ability of each formulation was evaluated using the Franz diffusion cell, with the conventional liposome (ML-1) without MEL as the control. The ML-4 formulation achieved a total retinol penetration of 29.0%, a 10.6% increase compared to ML-1 (18.4%). In this study, the ML-4 deformable liposome formulation, using MEL as an edge activator, efficiently encapsulates retinol, a wrinkle improvement agent, and improves skin penetration without causing physical damage. These findings suggest that ML-4 can serve as an efficient transdermal delivery system for functional cosmetic materials.

Advances in biotechnology have enabled highly effective, site-specific topical therapies for skin disease. Particle-based delivery systems can be engineered with tailored physicochemical properties and surface modifications to optimize controlled drug release and skin targeting, potentially improving acne treatment outcomes. To evaluate the effectiveness and tolerability of a retinol plus site-specific salicylic acid-targeted bio-delivery system in 40 Fitzpatrick skin type I-VI patients with moderate-to-severe acne over 12 weeks. Significant improvements were observed across multiple efficacy measures, including expert grading, microbiome analysis, visual imaging, and patient self-assessments. Investigator grading demonstrated a 27.8% reduction in inflamed pustules at 2 weeks and a 68.6% reduction at 12 weeks. Acne nodules improved by 61.1% at 2 weeks, with a 92.2% reduction by week 12. Post-inflammatory hyperpigmentation improved significantly beginning at week 2, with an overall 32.3% improvement at week 12. Microbiome analysis showed a 52% reduction in Cutibacterium acnes levels by week 12. Expert grading revealed no erythema by week 12 and no edema throughout the study period. Patients also reported no significant itching, burning, tingling, or stinging sensations during treatment. Combination therapy with site-specific acne medication and retinol produced significant clinical improvement in acne and post-inflammatory hyperpigmentation while demonstrating excellent tolerability over 12 weeks. &nbsp.

Aging is characterized by a progressive decline in physiological functions, including skin integrity and regeneration, with visible signs of skin aging typically emerging from the fourth decade of life onward. Extrinsic factors can accelerate this process. Retinoic acid has long been used as a standard anti-aging treatment, although it is associated with various side effects. L-ascorbic acid (LAA) 15% serum has emerged as a potential alternative with minimal side effects, yet its efficacy and safety in comparison to retinol 0.1% serum remain insufficiently studied. This double-blind, split-face, randomized clinical trial aimed to evaluate the effectiveness and safety of LAA relative to retinol in treating skin aging. Using the modified Dermoscopy Photo Aging Scale (DPAS) and JANUS-III, assessments were conducted on participants' cheeks. Results indicated significant improvements in both the LAA and retinol groups at weeks 2 and 4. However, no statistically significant differences were observed between the two interventions at these time points. Both treatments demonstrated similar safety profiles, suggesting that LAA is as effective and safe as retinol for anti-aging therapy.

Psoriasis is a chronic inflammatory disease often accompanied by metabolic syndrome. The function of AKR1B10 in the "metabolism-immune" interplay remains unclear. This study aimed to identify the role of AKR1B10 in pathogenesis and evaluate its inhibitor, Epalrestat, for psoriasis treatment via drug repurposing. Integrating GEO transcriptomic data, we screened for key metabolic signature genes. An imiquimod (IMQ)-induced murine psoriasis model was established to evaluate the efficacy and safety of intragastric and topical epalrestat, as assessed by PASI scores, histopathology, spleen index and body weight monitoring. Furthermore, RNA sequencing, functional enrichment analysis, protein-protein interaction analysis, immunofluorescence and RT-qPCR were performed to explore the underlying mechanisms. AKR1B10 was identified as a key differentially expressed gene positively correlating with activated DCs, neutrophils and Th17 cells (AUC = 0.970). In vivo, Epalrestat significantly ameliorated skin lesions, reduced PASI scores, and exhibited a safety profile superior to methotrexate(MTX). Mechanistically, Epalrestat treatment upregulated retinol metabolism while markedly suppressing the IL-17 signaling pathway. Epalrestat alleviates skin inflammation by inhibiting AKR1B10 activity, thereby restoring retinol homeostasis. The subsequent suppression of the IL-17 signaling axis is more likely a downstream consequence of improved metabolic status and a remodeled inflammatory microenvironment, rather than a direct effect. These findings support Epalrestat as a potential therapeutic agent for psoriasis that concurrently modulates metabolic and inflammatory pathways.

Retinol and salicylic acid are potent bioactive agents commonly used to treat skin pathologies such as acne, psoriasis, and photodamage. Their combined use offers synergistic therapeutic benefits. However, effective delivery of retinol remains challenging due to its poor aqueous solubility and rapid degradation under physiological conditions. In this study, a dual-delivery microsphere platform based on salicylic acid-derived poly(anhydride-ester)s (SAPAEs) was designed to co-release retinol and salicylic acid in a controlled and pH-responsive manner. Four SAPAE compositions with distinct degradation kinetics were synthesized via melt-condensation polymerization, incorporating different ratios of anhydride and ester linkages through copolymerization. Microspheres with reproducible size (∼10 µm) were formulated using an oil-in-water solvent evaporation method, achieving high salicylic acid loadings (54-77 wt%) via polymer composition and retinol loadings of 0.5-1.5 wt% through physical encapsulation. Thermodynamic predictions of retinol-polymer affinity showed reasonable agreement with experimental retinol loading results. Kinetic models applied to the release profiles confirm a surface-erosion mechanism for polymer degradation and subsequent salicylic acid release, while retinol release was mostly driven by diffusion. Faster release of both bioactive compounds were observed in basic solution. Among the formulations tested, the copolymer containing p-phenylenediacetic acid (PA) as the co-monomeric unit (SAA-co-PA) demonstrated the most controlled dual-release profile, with minimal retinol burst and sustained salicylic acid release. This tunable SAPAE-based microsphere platform offers a promising strategy for synergistic controlled delivery of multiple bioactive for skin pathologies and could be extended to other topical applications.

Retinol has emerged as a star ingredient in the cosmetics industry owing to its remarkable skincare efficacy. However, its major limitations-high irritation potential and chemical instability-necessitate further improvement. We developed a liposome primarily composed of glyceryl monooleate and poloxamer (F127). By hybridizing this with a binary alcohol system comprising a 1:1 (v/v) mixture of propylene glycol and dipropylene glycol, an ethosome (ES) capable of efficiently encapsulating retinol was obtained. Retinol-loaded ES (Ret-ES) was further modified with D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS@Ret-ES), thereby optimizing particle size distribution and drug loading capacity. Increasing the binary alcohol concentration from 10 to 30% caused TPGS@Ret-ES hydrated particle size to sharply decrease from 100 to 50 nm, without significant changes in drug loading or encapsulation efficiency. Compared with retinol aqueous solutions, TPGS@Ret-ES substantially reduced degradation rates at room temperature while maintaining excellent particle size stability. Additionally, incorporating antioxidants tocopheryl acetate and Irganox 1010 further improved chemical stability. Notably, TPGS@Ret-ES simultaneously enhanced transdermal drug permeation and skin retention, with no significant irritation observed following repeated application to the same skin site in guinea pigs. In conclusion, ES represents a highly promising topical delivery carrier, and TPGS@Ret-ES shows considerable potential as a novel formulation for retinol. Riboflavin (vitamin B2) is a water-soluble, heat-stable vitamin essential for cellular energy metabolism, acting as a precursor to the coenzymes flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). These cofactors are required by flavoproteins such as succinate dehydrogenase (Complex II), which participate in both the citric acid cycle and the mitochondrial electron transport chain, enabling adenosine triphosphate (ATP) production, maintaining redox balance, and supporting antioxidant defenses. Beyond energy metabolism, riboflavin contributes to immune function and to maintaining the health of skin, hair, and mucous membranes. Deficiency disrupts these pathways, leading to fatigue, normocytic anemia, neuromuscular symptoms, and secondary impairments in iron and other B-vitamin metabolism, including the activation of niacin (vitamin B3) and pyridoxine (vitamin B6). Because humans cannot synthesize riboflavin, adequate dietary intake is necessary, and absorption depends on normal gastrointestinal function. Excess riboflavin is excreted in urine, producing the characteristic yellow color that indicates adequate intake. Clinical deficiency is characterized by mucocutaneous manifestations (cheilosis, angular stomatitis, glossitis, dermatitis) and anemia; in severe or prolonged cases, it may lead to neurologic or ocular metabolic abnormalities, reduced physical performance, and developmental problems. Emerging evidence also links riboflavin deficiency to psoriasis, with decreased intake associated with a higher risk and upregulated riboflavin metabolism observed in psoriatic skin, suggesting a protective role for adequate riboflavin status, particularly in individuals older than 40 years. This article reviews the etiology, epidemiology, pathophysiology, clinical presentation, evaluation, management, complications, and prognosis of riboflavin deficiency. The article also highlights the roles of patient education and interprofessional healthcare team collaboration in optimizing patient outcomes.

Retinoids are a mainstay of dermatologic therapy. Although prescription retinoids are more potent than over the counter retinoids, when properly formulated cosmetic retinoids offer consumers an easily accessible, reasonably priced therapeutic option. Retinol has been shown to improve fine lines and wrinkles, hyperpigmentation, skin roughness, and the appearance of photoaged skin. The efficacy and tolerability of retinol makes it preferable to prescription retinoids as many patients are intolerant of these more potent forms. In this review, we will discuss the pharmacokinetics of retinol and the clinical studies confirming its efficacy, tolerability, and safety with long-term use. J Drugs Dermatol. 2022;21:7(Suppl):s4-10.

Aging of skin is an intricate biological process consisting of two types. While intrinsic or chronological aging is an inevitable process, photoaging involves the premature aging of skin occurring due to cumulative exposure to ultraviolet radiation. Chronological and photoaging both have clinically differentiable manifestations. Various natural and synthetic retinoids have been explored for the treatment of aging and many of them have shown histological and clinical improvement, but most of the studies have been carried out in patients presenting with photoaged skin. Amongst the retinoids, tretinoin possibly is the most potent and certainly the most widely investigated retinoid for photoaging therapy. Although retinoids show promise in the treatment of skin aging, irritant reactions such as burning, scaling or dermatitis associated with retinoid therapy limit their acceptance by patients. This problem is more prominent with tretinoin and tazarotene whereas other retinoids mainly represented by retinaldehyde and retinol are considerably less irritating. In order to minimize these side effects, various novel drug delivery systems have been developed. In particular, nanoparticles have shown a good potential in improving the stability, tolerability and efficacy ofretinoids like tretinoin and retinol. However, more elaborate clinical studies are required to confirm their advantage in the delivery of topical retinoids.

Kumkumadi Taila is a classical Ayurvedic facial oil traditionally used in primary care as a routine preventive skincare product to enhance the complexion; however, clinical instrument-based data and detailed chemical profiling remain scarce. In this single-arm 15-day exploratory study, 30 healthy adults with Fitzpatrick skin types III-IV applied Kumkumadi Taila once daily to the face using a standardized massage and wash-off procedure, while biophysical skin parameters and safety were monitored at baseline, Day 7, and Day 15 with an integrated DermaLab Combo ® device. Facial melanin index, erythema index, hydration, and elasticity showed statistically significant changes over time, whereas transepidermal water loss and skin thickness did not. This indicates short-term cosmetic improvement without detectable disruption of barrier integrity. Parallel UPLC-MS/MS QTOF analysis of the oil identified multiple bioactive phytochemicals, including safranal, berberine, palmatine, liquiritin, nuciferine, rubiadine, retinol, sesamin, and aliuretic acid, which are consistent with antioxidant, anti-inflammatory, and pigmentation-modulating actions reported in the literature. No adverse events were reported during the study. The results were statistically significant ( p < 0.05), indicating that the data deviates from a normal distribution and is skewed. Overall, Melanin and Erythema Index decreased significantly, indicating improved pigmentation and reduced redness. Skin elasticity declined over time, while skin hydration fluctuated. TEWL and skin thickness remained stable throughout the study. In this exploratory proof-of-concept assessment, short-term application of Kumkumadi Taila was associated with changes in selected facial skin biophysical parameters over 15 days. The study supports its potential as a safe and accessible primary care intervention in the form of a routine preventive skincare product, and its findings highlight the relevance of traditional Ayurvedic topical formulations in routine skin care. The study also demonstrates a practical framework for evaluating non-invasive skin metrics and phytochemicals, serving as a proof of concept.

Staphylococcus aureus is a major skin pathogen that causes a broad spectrum of infections, ranging from mild skin infections to severe invasive diseases. In this study, we evaluated antibacterial and antivirulence properties of selected FDA-approved skincare bioactives and antiseptics against multiple virulence factors. Minimum inhibitory concentration analysis of benzalkonium chloride, retinol, hydroquinone, and kojic acid showed strong antimicrobial activity at concentrations from 2 to 1024 µg/mL. Epigallocatechin gallate effectively inhibits biofilm formation by 81.53% and reduces staphyloxanthin production by 68.26%. Retinol exhibited antibiofilm activity, eradicating mature biofilm mass by 79.18%. Furthermore, a combination of skincare bioactives with antibiotics, including oxacillin, ciprofloxacin, tetracycline, and rifampicin, demonstrated synergy and additive effects, enhancing antibacterial efficacy. Molecular docking analysis exhibited strong predicted binding affinities of skincare bioactives and antiseptics against key virulence factors. This study highlights the multitarget antivirulence potential of skincare bioactives and antiseptics as an alternative strategy to mitigate diverse S. aureus infections.