Search Results (687)

Central nervous system (CNS) disorders represent a growing healthcare burden, and various drugs are developed for their treatment. However, the blood–brain barrier (BBB) prevents over 98% of therapeutics from reaching brain tissue. Intranasal delivery provides a promising alternative by exploiting olfactory and trigeminal nerve pathways to circumvent the BBB. This review surveys recent advances in nose-to-brain delivery technologies, from carrier design to evaluation methods. Polymeric and lipid-based nanocarriers show enhanced mucosal penetration and prolonged residence time, and microneedle platforms further enable controlled drug release with minimal discomfort. To evaluate these delivery strategies, sensor-integrated organ-on-chip models provide more physiologically relevant testing than static cultures. Although persistent challenges such as rapid mucociliary clearance and formulation stability remain, combining nanotechnology with microfluidic devices and computational modeling shows potential for developing patient-specific therapeutics. Full article

Background: Dermatology and aesthetic medicine make extensive use of microneedling, a minimally invasive and safe treatment. Across the research, it has been shown that microneedling combined with chemical peels is also more effective than chemical peels alone. However, data on procedures in dark-skinned individuals is rather scarce. Aim/Objective: This study aimed to determine the efficacy of using a 4% retinol solution product containing novel TGF-β activators and antioxidants combined with a microneedling technique in the treatment of hyperpigmentation, atrophic acne scars, and enlarged pores in patients with skin of color, generally corresponding to Fitzpatrick skin phototypes IV–VI. Methods: Each of the 10 patients underwent three peel treatment series, with a 30-day interval between each session. Moreover, skin hydration, elasticity, and pigmentation were examined using the Multi Skin Test MC 1000 Courage + Khazaka, and the Observ 520x device. Results: All patients reported an overall improvement and an enhancement in skin tone after the procedure. The majority of them stated subjective improvement in the reduction of facial skin issues: redness, hyperpigmentation, uneven structure, wrinkles, dehydration, dryness, and sebaceous gland activity. The least improvement was noted in scar reduction or liquidation. An objective evaluation revealed a statistically significant improvement in hyperpigmentation and elasticity in the study group. An improvement, however, not statistically significant, in hydration parameters was demonstrated during the study. Conclusions: This study suggests that a combined peel therapy of 4% retinol serum product containing novel TGF-β activators and antioxidants, together with a microneedling technique, may improve facial hyperpigmentation of the skin, as well as regulate sebaceous gland activity, their size, and reduce sebum production. The recommended method is relatively simple to use, low-cost, has minimal adverse effects, and is well tolerated by patients with skin of color. Full article

Personalized transdermal drug delivery systems (TDDS) represent a transformative approach in precision medicine by enabling patient-specific, non-invasive, and controlled therapeutic administration. Conventional transdermal patches are limited by fixed dosing, passive diffusion, and interindividual variability in skin permeability and metabolism, often leading to suboptimal therapeutic outcomes. Recent advances in materials science, nanotechnology, microneedle engineering, and digital health have enabled the development of next-generation personalized TDDS capable of programmable, adaptive, and feedback-controlled drug release. Smart wearable patches integrating biosensors, microfluidics, microneedles, and wireless connectivity allow real-time monitoring of physiological and biochemical parameters, enabling closed-loop drug delivery tailored to individual metabolic profiles. Nanocarriers such as lipid nanoparticles, polymeric nanoparticles, and stimuli-responsive hydrogels further enhance drug stability, penetration, and controlled release, while 3D-printing technologies facilitate patient-specific customization of patch geometry, drug loading, and release kinetics. Artificial intelligence (AI) and machine learning tools are increasingly being employed to predict drug permeation behavior, optimize enhancer combinations, and personalize dosing regimens based on pharmacogenomic and pharmacokinetic data. Despite these advances, regulatory complexity, manufacturing standardization, long-term biocompatibility, and cybersecurity considerations remain critical challenges for clinical translation. This review highlights recent innovations in personalized TDDS, discusses their clinical potential, and examines regulatory and technological barriers. Collectively, these emerging smart transdermal platforms offer a promising pathway toward adaptive, patient-centered therapeutics that can significantly improve treatment efficacy, safety, and compliance. Future research should focus on integrating multimodal biosensing, advanced biomaterials, scalable manufacturing strategies, and robust regulatory frameworks to enable clinically validated, fully autonomous transdermal systems that can dynamically adapt to real-time patient needs in diverse therapeutic settings. Full article

Diabetes mellitus affects an estimated 589 million adults globally, and cutaneous manifestations occur in up to 70% of affected individuals during the course of the disease. The objective of this narrative review is to examine the intersection of diabetes mellitus, skin aging, cosmetic dermatologic procedures, and regenerative therapies, with an emphasis on evidence-based best practices and clinical considerations. While the impaired wound healing associated with diabetes has been extensively studied, the aesthetic implications of diabetic skin disease remain comparatively underexplored. Individuals with diabetes frequently exhibit features of accelerated cutaneous aging, including premature wrinkling, dyschromia, xerosis, alopecia, and other cosmetically significant dermatoses that may negatively impact quality of life. In parallel, the demand for aesthetic dermatologic procedures among patients with diabetes has increased substantially; however, evidence-based recommendations guiding the safe and effective use of cosmetic interventions in this population remain limited. Diabetic skin demonstrates accelerated biological aging driven by complex pathophysiological mechanisms, including the accumulation of advanced glycation end products, chronic low-grade inflammation, oxidative stress, microvascular dysfunction, and neuropathy. These processes partially overlap with chronological aging and photoaging but are mechanistically distinct and may influence tissue repair, inflammatory responses, and the safety profile of commonly performed aesthetic procedures such as chemical peels, laser resurfacing, dermal fillers, neuromodulators, and microneedling. Emerging regenerative approaches, including platelet-rich plasma, platelet lysate, and mesenchymal stromal cell-derived products such as exosomes and secretomes, have attracted increasing attention as biologically targeted strategies for cutaneous rejuvenation. Nevertheless, clinical evidence specifically addressing aesthetic interventions in diabetic populations remains limited. A diabetes-informed approach to aesthetic dermatology that considers metabolic status, procedure selection, and post-procedural monitoring is therefore essential to optimize safety and therapeutic outcomes. Full article

Background/Objectives: Allergic conjunctivitis (AC) is the most common inflammatory disease affecting the ocular conjunctiva. Tacrolimus (TCR), a potent calcineurin inhibitor, is limited by poor aqueous solubility and low ocular bioavailability. This study aimed to develop TCR-loaded cubosomes (TCR-Cubs) incorporated into HPMC/PVP K90 dissolving microneedles (MNs) to enhance their therapeutic efficacy. Methods: TCR-Cubs were prepared using a modified top-down fragmentation method with glyceryl monooleate and poloxamer 407, optimized via Box–Behnken design, and incorporated into dissolving MNs. The system was evaluated in vitro, ex vivo, and in vivo using a rabbit model of allergic conjunctivitis. Results: The optimized formulation exhibited the smallest particle size (210 ± 0.91 nm), polydispersity index (0.29 ± 0.03), zeta potential (−21 ± 0.87 mV), and the highest entrapment efficiency (% 93.3 ± 0.45). The optimized formulation was incorporated into MNs via micro molding. Scanning electron microscopy (SEM) confirmed well-defined, sharp microneedles, with low height reduction (<10%) by mechanical testing and high penetration efficiency (>85–90%). In vitro release studies revealed sustained drug release of (~75–80%) over 24 h, compared to (~40%) from the TCR suspension, following diffusion-controlled kinetics. Ex vivo permeation studies showed a (~2–3-fold) enhancement in corneal drug flux. In vivo pharmacodynamic evaluation using an ovalbumin-induced allergic conjunctivitis model demonstrated significant reductions in inflammatory mediators, including inflammatory markers (TNF-α, IL-1β, IL-6, NLRP3), which were reduced by (~50–75%), with modulation of CPA3, BCL2, and TGF-β1 by qRT-PCR. Histopathology and TLR4 analysis confirmed reduced inflammation without irritation. Conclusions: This dual-delivery system offers a promising, non-invasive platform for enhanced ocular delivery of tacrolimus with superior anti-inflammatory efficacy in allergic conjunctivitis. Full article

Background: Conventional therapies for moderate-to-severe inflammatory acne include topical agents, systemic antibiotics, hormonal treatments, and oral isotretinoin. However, increasing resistance of Cutibacterium acnes to antibiotics and the potential adverse effects of systemic agents have prompted growing interest in non-pharmacological alternatives such as fractional microneedling radiofrequency (RF-MN), recently introduced in the clinical practice. Objective: This report of five cases aims to document the clinical benefits and safety of RF-MN using the Focus Dual^® device in the treatment of moderate-to-severe inflammatory acne vulgaris. Methods: Five patients (2 male, 3 female; aged 19–28 years; Fitzpatrick skin types II–III) with moderate-to-severe acne were treated with two RF-MN sessions at 4-week intervals using the Focus Dual^® device (Med & Tech, Occhiobello (RO), Italy). Acne severity was assessed using the Face Global Acne Grading System (F-GAGS) and the 5-point Global Improvement Score (GIS), with evaluations performed by two independent blinded raters (G.P and O.R). Standardized photographic documentation and lesion counting were conducted at baseline (T0) and 4 weeks after the second session (T2). All individual F-GAGS scores for each of the five patients showed a reduction from baseline to T2, as consistently assessed by both evaluators. Two patients improved from moderate to mild acne, one improved from severe to moderate, and one remained mild. GISs indicated clinical improvement ranging from Grade 1 to Grade 2 in all cases, with individual improvements between 8.33% and 37.93%. No adverse events were reported during treatment or follow-up. Conclusions: RF-MN appears to be a promising therapeutic option for moderate-to-severe inflammatory acne, providing clinical improvement and reduction in acne severity without adverse effects. Prospective studies with a larger sample are needed to confirm these preliminary results and support the potential role of RF-MN as an adjunctive or standalone treatment in patients with limited tolerance or response to conventional therapies. Full article

Background/Objectives: Platelet-rich plasma (PRP)–based regimens are widely used in non-scarring alopecia, yet objective response is variable and clinic-ready predictors are lacking. We evaluated short-term trichoscopic outcomes in routine practice and tested whether baseline complete blood count–derived inflammatory status, quantified by the neutrophil-to-lymphocyte ratio (NLR), can stratify response under PRP-based therapy. Methods: We performed an ambispective observational cohort study (October 2024–October 2025) in an outpatient dermatology practice. The final analytic cohort included 129 patients allocated to four treatment groups: PRP alone (n = 54), PRP combined with microneedling-assisted Purasomes Hair & Scalp Complex (HCS50+, Dermoaroma; exosome-containing) (n = 33), PRP combined with microneedling-assisted Mesoaroma Hair Cocktail (scalp formulation; nutrient complex) (n = 24), and a nutrient complex alone (n = 18). Trichoscopy (FotoFinder ATBM; FotoFinder Systems GmbH, Bad Birnbach, Germany) was obtained at baseline (T1) and first follow-up (T2). Density response was defined as a ≥10% increase in total hair density and hair-cycle response as an anagen fraction increase ≥5 percentage points. Predictive analyses were prespecified and restricted to PRP-containing regimens, using logistic regression and a multilayer perceptron with repeated cross-validation for internal validation. Results: Across the full cohort (n = 129), total hair density and hair-cycle parameters improved from T1 to T2. In the PRP-containing subgroup (n = 111), baseline NLR strongly discriminated density responders (AUC 0.85, bootstrap 95% CI 0.77–0.91). In multivariable models, NLR remained independently associated with density response (OR 0.31 per 1-unit increase, 95% CI 0.20–0.48). Conclusions: In this cohort, baseline NLR was associated with discrimination of early trichoscopic response in PRP-based treatment of non-scarring alopecia. Using the Youden-derived cut-off (NLR = 2.202), patients with NLR > 2.202 had a higher risk of density non-response (72.1% vs. 4.7%), corresponding to a 15.49-fold increased failure risk in this cohort. These findings are exploratory and hypothesis-generating, and external validation and calibration are required before any routine clinical or decision-support use. Full article

Polymer-based biosensors have evolved from passive supports into active functional elements that dictate analytical performance in complex real-world samples. This critical review with meta-trend analysis examines 96 original research articles published between 2015 and 2025, evaluating how four polymer classes (conductive polymers, redox-mediator polymers, hydrogels, and molecularly imprinted polymers) address matrix effects in food, beverage, environmental and clinical applications. Electrochemical detection dominates (79% of studies), with conductive polymers enabling low-potential operation that excludes electroactive interference. Hydrogels achieve superior precision (RSD below 3%) in protein-rich matrices through biocompatible microenvironments that preserve enzyme kinetics. Molecularly imprinted polymers provide unmatched stability in harsh environments for trace-level detection of heavy metals and toxins, though delayed response times from slow analyte diffusion persist. Critical evaluation exposes validation deficits: 91% of studies omit limits of quantification, while approximately one-third lack reproducibility (33%) and precision (30%). The multi-matrix challenge, maintaining calibration across different hostile environments, remains the primary barrier to commercial deployment. Advanced architectures, including nanocapsulation, hierarchical nanocomposites, and microneedle-integrated systems, offer pathways to overcome limitations in fouling resistance and operational stability. Full article

Despite advancements in clinical diagnostics, traditional biomarker detection methods (e.g., ELISA) remain limited due to their invasive nature, slow results, and inadequate use for continuous monitoring in low-resource settings. With the rise in chronic, infectious, and metabolic diseases, there is a pressing demand for real-time, minimally invasive diagnostic tools. Nanoengineered microneedle (MN) biosensors offer a promising solution. These painless devices can access interstitial fluid (ISF), a rich source of biomarkers, while utilizing advanced nanomaterials for high sensitivity and multiplexed detection. When combined with AI, IoT connectivity, and cloud-based analytics, MN biosensors enable personalized health data and continuous disease management. This review outlines recent advances in MN technology, including innovations in design and nanomaterial integration, as well as translational challenges like manufacturing scalability and regulatory approval. We explore how MN designs incorporating various sensing modalities can facilitate real-time monitoring of biomarkers such as glucose, lactate, and inflammatory proteins. Importantly, we discuss how these devices can improve healthcare access, reduce costs, and empower patients through everyday monitoring. This review integrates developments in MN engineering with biosensing and therapeutics, positioning biosensor-integrated MNs as pivotal in enabling continuous, minimally invasive disease monitoring and personalized therapy beyond traditional hospital environments. Full article

Phagocytosis and migration in macrophages share key regulators, including Rho family GTPases; however, whether phagocytic membrane extension generates a transient, whole-cell polarity that coordinates migration and spatial prioritization of engulfment remains unclear. Here, we investigated the spatiotemporal coupling between membrane extension and cell migration using opsonized microneedles, which enable controlled stimulation together with long-range membrane extension and backtracking dynamics. During single-needle stimulation, membrane extension was tightly coupled to directional migration, whereas membrane retraction showed weaker coupling. In sequential stimulation with two microneedles, ongoing phagocytosis suppressed competing membrane extension at spatially opposite locations, and a reversal in migration direction was accompanied by initiation of membrane extension toward the second needle. Third-needle experiments further revealed a polarized spatial distribution of phagocytic responsiveness across the cell surface. Consistently, uniform stimulation with multiple opsonized microbeads demonstrated sequential, one-at-a-time engulfment even under near-simultaneous target attachment. These results support a model in which phagocytic membrane extension establishes transient, whole-cell polarity that spatially gates engulfment and coordinates whole-cell migration. The microneedle manipulation platform provides a powerful approach for dissecting the spatiotemporal regulation of phagocytosis and for understanding macrophages as adaptive living micromachines integrating mechanical inputs, transient polarity formation, and sequential target processing. Full article

Background: The global spread of monkeypox virus (MPXV) highlights an urgent need for thermostable and easily administrable vaccines. Current orthopoxvirus vaccines are limited by cold-chain dependence and inconvenient injection-based delivery. Objectives: This study aimed to develop a dissolvable microneedle (DMN) vaccine against monkeypox based on a replication-deficient orthopoxvirus platform, through systematic formulation screening, stabilization mechanism exploration, and rigorous in vivo immunogenicity evaluation. Methods: A film-based approach was adopted for efficient, high-throughput formulation screening and thermostability assessment. NTV was mixed with excipients and dried into solid films. Stability was monitored via RT-qPCR after storage at 4 °C to 40 °C. The lead formulation was physically characterized, then used to fabricate MVA-BN-loaded DMN patches, which were further evaluated for in vivo immunogenicity via immunization in BALB/c mice. Results: The optimal formulation F2 (containing dextran, L-threonine, and BSA/HSA) showed a potency loss of only ~1 log₁₀ after 2 months at 25 °C, and <1 log₁₀ loss after 1 week at 37 °C. SEM revealed a porous virus-entrapment morphology, and FTIR indicated enhanced hydrogen bonding between the virus and the dextran matrix. The formulation was successfully manufactured into DMNs that dissolved within 5 min. In mice, these DMNs elicited robust MPXV-specific IgG and neutralizing antibody responses, with immunogenicity comparable to that induced by conventional intramuscular injection. Conclusions: This study successfully established a thermostable formulation and dissolvable microneedle delivery platform for replication-deficient orthopoxvirus vaccines against monkeypox. The optimized DMN vaccine induced robust MPXV-specific immune responses in mice with immunogenicity comparable to intramuscular injection, addressing the core limitations of current vaccines and providing a promising solution for monkeypox prevention. Full article

Patients receiving dialysis treatments suffer from a high rate of systemic comorbid conditions, including cardiovascular disease, mineral and bone disorders, chronic inflammation, amyloidosis, and recurring infections, leading to increased morbidity and mortality rates despite the progress made in the field of renal replacement therapies. The aforementioned conditions result from the continued dysregulation and overproduction of molecular biomarkers, which cannot be adequately monitored by traditional, intermittent laboratory tests. This review critically assesses the newly developed biosensor technologies for the detection of major dialysis biomarkers, including potassium, phosphorus, parathyroid hormone (PTH), β₂-microglobulin, creatinine, and cystatin C, with special emphasis on biosensors based on electrochemistry, optics, impedimetry, nanophotonics, and biological engineering techniques. These recent biosensors have been evaluated based on their analytical performance, the biofluids used in the studies, and their suitability for measuring relevant concentrations of these biomarkers. Special attention is given to biosensors capable of continuous operation or minimally invasive sampling, as well as to newly developed biofluid sampling techniques, including microneedle-, microtube-, and micropillar-based systems, for the long-term monitoring of the biomarkers in the serum of patients receiving dialysis treatments. The biosensing techniques for measuring infection biomarkers have also been discussed, given the high risk of bloodstream and access infections among patients receiving dialysis. The limitations of these biosensors include biofouling, calibration drift, and their integration into the dialysis treatment workflow. Finally, the future prospects of the recent biosensors offer the possibility of the proactive management of the high rate of comorbid conditions in this high-risk population of patients receiving dialysis treatments. Full article

Natural and sustainable cosmetics represent a rapidly evolving frontier in dermatological science, integrating plant-derived bioactive compounds with advanced delivery technologies and environmentally conscious formulation design. Botanical ingredients, including polyphenols, flavonoids, terpenoids, alkaloids, and polysaccharides, modulate key biological pathways involved in oxidative stress, inflammation, extracellular matrix remodeling, pigmentation, and immune responses, thereby supporting skin regeneration, protection, and homeostasis. To overcome limitations related to instability, compositional variability, and limited skin penetration, these compounds are increasingly incorporated into advanced delivery systems such as nanoemulsions, solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), vesicular systems, microneedle platforms, three-dimensional matrices, and plant-derived extracellular vesicles (PDEVs). These technologies enhance cutaneous bioavailability, enable controlled release, and improve tissue targeting, linking formulation design to exposure–response relationships. In parallel, sustainability has become a critical component of product development. Circular economy strategies, including the upcycling of agro-industrial by-products, green extraction technologies, biodegradable packaging, and life cycle assessment, are reshaping cosmetic innovation. Regulatory frameworks are also evolving to address safety, efficacy, and transparency of natural claims, as well as the challenges of botanical standardization. This narrative review, conducted through a structured literature search, provides a mechanistically oriented analysis of botanical ingredients in dermatology, emphasizing molecular pathways, skin delivery science, and safety considerations. Rather than cataloguing ingredients, it proposes a translational framework linking phytochemistry, delivery science, safety-by-design principles, and sustainability to support the rational development of effective and safe dermatological formulations. Full article

Transcutaneous electrical nerve stimulation (TENS) is constrained by high skin impedance and unstable electrode contact. This study proposes a novel composite electrode system comprising a polyvinyl alcohol/silver (PVA/Ag) microneedle array and a highly conductive polyacrylamide/lithium chloride (PAAm/LiCl) hydrogel. The PVA/Ag microneedles (~365 µm in height, ~48 µm tip diameter) possess sufficient mechanical strength to penetrate the stratum corneum, establishing a low-resistance pathway. The complementary PAAm/LiCl hydrogel exhibits high conductivity (10.28 S/m) and mechanical flexibility, further optimizing the interface contact. The experimental results demonstrate that this composite system achieves low electrochemical impedance and induces stable, clear electromyographic responses in vivo. It effectively addresses the common issues of electrode detachment and signal attenuation associated with conventional electrodes, offering a promising hardware solution for efficient and comfortable wearable rehabilitation devices. Full article

Background: Acne scars remain a very common complaint in dermatology practices. Even though many treatment options are available, proper treatment remains a challenge. Complex treatment methods that are based on the synergy effect are the ones that result in better effects and patient satisfaction. Methods: Three healthy female patients with a total of 106 atrophic acne scars were recruited to the split-face study with placebo control, where a series of three microneedling procedures in monthly intervals combined with 5% retinyl palmitate-loaded oleogel was compared to the same microneedling protocol with placebo. Patients’ quality of life was measured using the Dermatology Life Quality Index (DLQI) and Skindex-29 questionnaires. Patients’ satisfaction with treatment and intensity of post-procedure symptoms were assessed as well. Results: In clinical evaluation, a modest effect was observed regarding the reduction in atrophic acne scars, whereas moderate-to-marked improvement in acne scar reduction was noted by the patients. Additionally, mild to marked improvement was noted by patients regarding skin quality, moisture level, elasticity, and skin tone. No significant side effects were noted. All the above resulted in good patient satisfaction with the treatment, and willingness to repeat the procedures again. No significant differences regarding acne scar reduction, treatment-related symptoms, and skin quality improvement were noted between active substance and placebo-treated sides of the face. Conclusions: Microneedling remains a key method in the therapeutic arsenal for acne scarring. By combining it with 5% retinyl palmitate-loaded oleogel modest effects can be noted after a series of three procedures, with good overall treatment tolerability and patients’ satisfaction. Full article