Search Results (164)

Transferosomes are liposome-derived ultradeformable vesicles designed to improve drug delivery across restrictive biological barriers, particularly in non-invasive administration routes. Their structure is based on phospholipid bilayers modified with edge activators, usually surfactants or bile salts, which increase membrane flexibility while preserving vesicular organization. This balance between deformability and stability distinguishes transferosomes from conventional liposomes and has supported their use in dermal, transdermal, ocular, nasal, buccal, and other mucosal delivery systems. However, despite extensive experimental interest, the field remains limited by inconsistent terminology, heterogeneous formulation strategies, non-harmonized deformability assays, and incomplete translation from laboratory formulations to clinically relevant products. This review critically examines transferosomes from a formulation-development perspective, focusing on the relationship between lipid composition, edge-activator selection, vesicle properties, deformability, drug release, and biological performance. Particular attention is given to critical quality attributes, analytical characterization, mechanistic interpretations of barrier interaction, and the unresolved debate between intact vesicle penetration, drug-release-dominated delivery, and barrier perturbation. Transferosomes are also positioned in comparison with conventional liposomes, ethosomes, and transethosomes. Finally, the review identifies key unmet needs related to standardization, reproducibility, scalability, storage stability, and regulatory uncertainty. By integrating formulation design with mechanistic and translational analysis, this review aims to clarify when transferosomes offer a genuine delivery advantage and which parameters must be controlled to support their further pharmaceutical development. Full article

Background: Menopausal hormone therapy (MHT) effectively relieves vasomotor symptoms, but its cardiovascular safety remains influenced by timing, formulation, and route of administration. Methods: This narrative review summarizes evidence from major randomized trials (WHI, HERS, ELITE, DOPS) and observational studies, along with mechanistic data on the vascular and metabolic effects of MHT. Results: Although early studies suggested cardioprotection, randomized trials showed no cardiovascular benefit, and in some cases, increased risks of coronary events, stroke, and venous thromboembolism, particularly in older women or those with established cardiovascular disease. The “timing hypothesis” indicates that early initiation after menopause may have neutral or modestly favorable effects, whereas late initiation is associated with adversity. Oral estrogen is linked to higher thromboembolic and stroke risk compared with transdermal formulations. Evidence on atrial fibrillation and heart failure remains limited. Conclusions: MHT should not be used for cardiovascular disease prevention. Current evidence suggests that younger women in the early postmenopausal period may derive the greatest benefit with the lowest risk from individualized hormone therapy regimens, particularly those using transdermal estrogen. Treatment decisions should be guided by careful cardiovascular risk assessment and targeted to symptom relief and osteoporosis prevention. Full article

Background: A transdermal drug delivery system has significant benefits over conventional routes; however, its effectiveness is limited by the barrier properties of the stratum corneum. Dissolving microneedles (DMNs) have emerged as a minimally invasive strategy to enhance drug permeation while improving patient compliance. The integration of advanced fabrication techniques such as 3D printing enables precise control over microneedle geometry and reproducibility. Objective: This study aimed to fabricate and characterize pregabalin-loaded PVA/PVP dissolving microneedle arrays using a 3D-printing-assisted mold fabrication approach for efficient transdermal drug delivery. Methods: Microneedle master molds were fabricated using 3D printing, followed by replication using polydimethylsiloxane (PDMS) to obtain negative molds. Pregabalin-loaded bilayer microneedles were prepared using a micromolding technique with PVA/PVP polymers. The formulation was evaluated through rheological analysis, scanning electron microscopy (SEM), mechanical strength testing, insertion studies, swelling behavior, drug loading efficiency, Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and in vitro drug release studies. Results: The fabricated microneedles exhibited uniform geometry with sharp tips and no structural defects. Rheological analysis confirmed shear-thinning behavior suitable for mold filling. The microneedles demonstrated adequate mechanical strength (~3.3 N/needle) and efficient insertion into the parafilm model. Drug loading efficiency was high (92.4%), indicating effective encapsulation. FTIR analysis confirmed compatibility between drug and polymers, while DSC and XRD results indicated partial amorphization of pregabalin within the polymer matrix. The formulation showed a biphasic drug release profile with an initial burst followed by sustained release, achieving ~96.8% cumulative release over 24 h. Conclusions: The study successfully demonstrates a robust and reproducible 3D-printing-assisted approach for fabricating pregabalin-loaded dissolving microneedles. The developed system exhibited desirable mechanical, physicochemical, and drug release properties, highlighting its potential as an effective transdermal drug delivery platform. Full article

Objective: Self-assembled nanoparticles (SANs) naturally occurring in Traditional Chinese Medicine (TCM) decoctions are promising drug carriers due to their biocompatibility, but uncontrolled assembly often leads to poor stability, limiting transdermal permeability and industrial application. This study aimed to fabricate stable and uniform SANs from licorice by precisely regulating the controlled nanoprecipitation of its water- and alcohol-extracted components. The transdermal delivery efficiency and therapeutic efficacy of the SANs in the treatment of atopic dermatitis (AD) were evaluated. Methods: Licorice self-assembled nanoparticles (LD-SANs) were prepared by mixing water and ethanol extracts of licorice, followed by ethanol evaporation under reduced pressure to trigger nanoprecipitation. In vitro transdermal tests compared the delivery efficiency of six major bioactive compounds between LD-SANs and traditional licorice decoction (LD). The penetration mechanism was investigated via passive diffusion and cellular uptake studies. In an AD mouse model, the therapeutic effects and expression of tight junction (TJ) proteins (Occludin and Claudin-1) were assessed. Results: The average particle size of LD-SANs is 200 nm, and it is uniform and stable. LD-SANs significantly enhanced the delivery efficiency of all six bioactive compounds compared to LD. Mechanistic studies revealed a unique “dual-channel” penetration mechanism: the nanoscale size enabled passive diffusion through hair follicles, intercorneocyte lipid gaps, and skin appendages, while perifollicular antigen-presenting cells (APCs) actively recognized and internalized the nanoparticles, creating a cell-mediated active targeting route that collectively boosted skin accumulation. In the AD model, LD-SANs promoted the expression of Occludin and Claudin-1 in the epidermal granular layer, reinforcing intercellular barrier integrity. Conclusions: By combining “efficient penetration” and “barrier repair”, LD-SANs demonstrated notable therapeutic efficacy in AD. This work transforms a traditional decoction into a well-characterized, high-performance nanomedicine and offers a novel strategy for developing TCM-based transdermal delivery systems. Full article

Maintaining hormonal equilibrium is a key determinant of women’s health, particularly during the menopausal transition and postmenopause. The decline in ovarian estrogen and progesterone production influences multiple physiological systems, affecting many aspects like vasomotor stability, bone and cardiovascular health, cognitive function, mood, and metabolic regulation. As a result, many women may experience symptoms that impair daily functioning and increase long-term morbidity. Recent progress in menopausal care emphasizes individualized, evidence-guided treatment, supported by improved diagnostic tools that allow for a more precise assessment of endocrine changes during this life stage. Among the available therapeutic options, transdermal menopausal hormone therapy has gained growing recognition due to its ability to re-establish hormonal levels with fewer systemic effects. By bypassing first-pass hepatic metabolism, this route provides more consistent serum hormone concentrations and may be associated with a lower risk of metabolic and thromboembolic complications compared with oral formulations. This review brings together the physiological basis, clinical indications, and current scientific evidence related to transdermal hormonal therapy during menopause while also highlighting its expanding therapeutic role and integration into personalized treatment strategies. In addition, we discuss recent findings on its pharmacological profile, clinical effectiveness, and emerging perspectives that position this therapeutic option as an increasingly important component of modern menopausal care and women’s health management. Full article

Background/Objectives: Skin cancers belong to the most frequent cancer type with over a million cases per year. Presently, transdermal drug delivery systems (TDDS) are an attractive drug delivery route, but they still face some limitations due to the resistance of human skin. Methods: Here, Sonidegib, PEDOT:PSS, and gelatins were employed as the model drug, drug carrier, and drug matrix, respectively. Results: Gelatin hydrogels were fabricated via the physical crosslinking to avoid toxicity towards the human skin. PEDOT:PSS was synthesized by chemical oxidative polymerization as the drug carrier. Sonidegib first interacted with PEDOT:PSS before they were embedded into the gelatin hydrogels. In the release and release-permeation experiments, the amounts of Sonidegib released and permeated were investigated under the effects of gelatin types, concentrations, pH values, PEDOT:PSS, and electrical voltages. For the effect of gelatin types, the BG gelatin provided higher amounts of Sonidegib release than PG from the higher electrorepulsive force. Under applied electrical voltages and with PEDOT:PSS present, the amounts of Sonidegib release and release-permeation amounts increased as PEDOT:PSS assisted in providing higher electroosmosis and electrorepulsive forces. Conclusions: In summary, PEDOT:PSS in the BG hydrogel is demonstrated here as a potential drug carrier to improve the Sonidegib release and release-permeation iontophoretically for TDDS. Full article

Background and Objectives: Menopausal hormone therapy (MHT) is the most efficacious treatment for vasomotor symptoms and genitourinary conditions associated with menopause. Modern menopause care increasingly encompasses women with multimorbidity, renal or hepatic impairment, previous malignancies or thromboembolic disorders, advanced age, and polypharmacy—groups frequently underrepresented in randomized clinical trials. This evidence gap prompts significant inquiries about the relevance of trial-based recommendations to actual clinical practice. Materials and Methods: This narrative review offers a concentrated assessment of prominent worldwide clinical guidelines regarding menopausal hormone therapy through thematic synthesis. We examined position statements from the North American Menopause Society (NAMS), the European Menopause and Andropause Society (EMAS), NICE clinical guidelines, the ACOG Practice Bulletin on menopausal symptom management, the Endocrine Society clinical practice guideline, and pertinent UK guidance from RCOG, BMS, and BGCS. Data from systematic reviews, meta-analyses, and extensive observational studies were analyzed to contextualize guideline recommendations for populations often underrepresented in clinical trials, including women aged ≥65 years and individuals with multimorbidity or polypharmacy. Results: Only the NICE and EMAS recommendations expressly acknowledge clinical vulnerability or complexity (multimorbidity, frailty, and cancer survivorship) as foundational principles. NAMS and ACOG delineate risk categories but fail to offer a cohesive taxonomy of vulnerability. Polypharmacy and drug–drug interactions are inconsistently addressed across guidelines, and there is a deficiency of standardized prescribing algorithms. While routine safety monitoring is universally advocated, the intervals for follow-up and methods for risk categorization differ. Observational evidence consistently indicates route-dependent variations in cardiovascular and thromboembolic risk, with transdermal estrogen linked to a more advantageous safety profile in higher-risk individuals. Conclusions: Present menopausal therapy guidelines are methodologically sound; however, they insufficiently address the complexities of multimorbidity, polypharmacy, and organ dysfunction. A systematic conceptual framework that incorporates areas of clinical vulnerability may facilitate personalized benefit–risk evaluation in practical applications. Future guideline revisions should enhance clarity by incorporating polypharmacy concerns, monitoring strategies, and systematic risk stratification methods for clinically complicated patients. Full article

Background/Objectives: Migraine is a leading cause of disability in women and is intricately linked to hormonal fluctuations and systemic health. This review aims to unravel the complex relationship between migraine, cardiovascular disease, and metabolic syndrome throughout the female reproductive lifespan. Methods: A comprehensive narrative review was conducted using the PubMed database for studies published between January 1988 and December 2025. Keywords included “migraine”, “cardiovascular risk”, “metabolic syndrome”, “pregnancy”, and “hormonal therapy”. Articles were selected to synthesize the latest pathophysiological evidence and clinical guidelines. Results: Migraine prevalence in women is two to threefold higher than in men, peaking during fertile age. Hormonal milestones, particularly estrogen withdrawal, trigger menstrual migraine. Metabolic syndrome is significantly more common in migraineurs than the general population. Obesity and insulin resistance have been associated with higher migraine attack frequency and severity. Experimental evidence suggests that hyperinsulinemia may sensitize TRPV1 receptors on trigeminal neurons and enhance CGRP release, potentially lowering the activation threshold for migraine attacks; however, direct confirmation of this pathway in humans remains limited. Furthermore, migraine with aura is linked to a doubled risk of ischemic stroke and increased risk of cardiovascular events. In pregnancy, migraine is an independent risk factor for stroke, myocardial infarction, and spontaneous coronary artery dissection. Conclusions: Migraine is a critical marker for cardiovascular and metabolic risk, necessitating routine screening and multidisciplinary management. Clinicians must prioritize cardiovascular counselling, metabolic evaluations, and careful monitoring in these patients, especially during pregnancy. Hormonal therapy choices should be individualized, preferring progestin-only contraceptives for those with aura and transdermal routes for hormone replacement therapy to minimize cardiometabolic impact. Full article

Insulin therapy remains essential for the management of diabetes mellitus; however, conventional subcutaneous injection continues to impose significant physical, psychological, and behavioral barriers that negatively affect treatment adherence and metabolic outcomes. Injection-related pain, fear of needles, local tissue complications, and psychological insulin resistance contribute to delayed insulin initiation, inadequate dose titration, and suboptimal glycemic control worldwide. In response, alternative insulin delivery routes (including oral, pulmonary, nasal, and transdermal strategies) have been explored to reduce invasiveness and improve patient experience. Among these, transdermal insulin delivery has emerged as a particularly promising approach due to its potential to bypass gastrointestinal degradation, provide controlled absorption, and enhance patient acceptance. Recent advances in microneedle-based systems and needle-free jet injectors have enabled effective transdermal insulin administration by overcoming the skin barrier while minimizing pain and discomfort. This narrative review synthesizes current evidence on insulin delivery technologies with a specific focus on transdermal and needle-free systems. We discuss the biological and physicochemical challenges of insulin transport, the mechanisms underlying emerging delivery platforms, and clinical evidence regarding metabolic efficacy, glycemic variability, and patient-reported outcomes. The integration of these technologies with continuous glucose monitoring is also explored. Finally, we address translational challenges and future perspectives, highlighting the role of needle-free insulin delivery as a patient-centered strategy to improve adherence and metabolic control in diabetes care. Full article

Controlled drug delivery systems (CDDSs) are increasingly attracting interest from the scientific community in order to achieve highly precise, customized, and efficient therapeutic treatment of various diseases. The challenge is to develop highly innovative devices and appropriate administration methods in order to reduce side effects and further improve patient compliance. In this context, transdermal drug delivery systems (TDDSs) represent smart tools that permit supplying therapeutically effective amounts of drugs at a fixed time using the skin as the administration route. They are non-invasive and allow for avoiding gastric side effects and first-pass metabolism occurring in the liver. TDDSs have been produced using numerous therapeutic agents and, more recently, also biological molecules. However, it must be highlighted that they are complex systems, and their formulation requires a multidisciplinary approach and expertise in polymer chemistry and materials science. A contribution in this direction is given from the integration of membrane technology with biological and pharmaceutical sciences. The present review deals with a general overview of controlled drug delivery systems. Particular attention is devoted to TDDSs and to the materials used for producing polymeric membrane-based TDDSs with a membrane engineering perspective. It also describes the passive and the most advanced active strategies for transdermal delivery. Finally, different transdermal membrane-based release systems, like patches, mixed-matrix membranes, and imprinted membranes are discussed. Full article

Background/Objectives: Abaloparatide is an osteoanabolic therapy used in patients at high risk of fracture; however, the breadth of evidence across routes, comparators, and sequential strategies has not yet been comprehensively summarized. This study aimed to evaluate the efficacy and safety of abaloparatide for reducing fractures and improving bone mineral density (BMD) in adults with osteoporosis. Methods: Following PRISMA 2020, we searched PubMed, Embase, CENTRAL, and Web of Science (2016–2024) for randomized controlled trials and comparative real-world studies. Additional meta-analyses and network meta-analyses were included as contextual evidence but not pooled to avoid double-counting. Primary outcomes were vertebral, non-vertebral, and hip fractures; secondary outcomes included percentage change in BMD and safety endpoints. Random-effects models were used; heterogeneity, influence analyses, and prediction intervals were examined. Risk of bias was assessed using RoB 2 and AMSTAR 2. Results: Nine quantitative evidence sources met the criteria. Abaloparatide reduced vertebral fractures (RR 0.13–0.21) and showed moderate reductions in non-vertebral fractures. Lumbar spine BMD increased substantially, while hip and femoral neck gains were smaller and heterogeneous. Hypercalcemia risk was consistently lower compared to teriparatide. Transdermal delivery was less effective, and sequential abaloparatide → antiresorptive therapy further reduced fractures. Serious adverse events were not increased. Conclusions: Abaloparatide provides strong vertebral protection, significant BMD improvement, and shows a favorable calcemic profile, with moderate certainty for non-vertebral effects. Evidence in men and long-term safety remains limited. Full article

Microneedle (MN) technologies have emerged as a groundbreaking platform for transdermal and intradermal drug delivery, offering a minimally invasive alternative to oral and parenteral routes. Unlike passive transdermal systems, MNs allow the permeation of hydrophilic macromolecules, such as peptides, proteins, and vaccines, by penetrating the stratum corneum barrier without causing pain or tissue damage, unlike hypodermic needles. Recent advances in materials science, microfabrication, and biomedical engineering have enabled the development of various MN types, including solid, coated, dissolving, hollow, hydrogel-forming, and hybrid designs. Each type has unique mechanisms, fabrication techniques, and pharmacokinetic profiles, providing customized solutions for a range of therapeutic applications. The integration of 3D printing technologies and stimulus-responsive polymers into MN systems has enabled patches that combine drug delivery with real-time physiological sensing. Over the years, MN applications have grown beyond vaccines to include the delivery of insulin, anticancer agents, contraceptives, and various cosmeceutical ingredients, highlighting the versatility of this platform. Despite this progress, broader clinical and commercial adoption is still limited by issues such as scalable and reliable manufacturing, patient acceptance, and meeting regulatory expectations. Overcoming these barriers will require coordinated efforts across engineering, clinical research, and regulatory science. This review thoroughly summarizes MN technologies, beginning with their classification and drug-delivery mechanisms, and then explores innovations, therapeutic uses, and translational challenges. It concludes with a critical analysis of clinical case studies and a future outlook for global healthcare. By comparing technological progress with regulatory and commercial hurdles, this article highlights the opportunities and limitations of MN systems as a next-generation drug-delivery platform. Full article

Symptomatic male hypogonadism, defined by low serum testosterone with associated clinical symptoms, is increasingly treated with testosterone replacement therapy. Traditional oral formulations were limited by hepatotoxicity and poor bioavailability, leading to reliance on injectable and transdermal routes. Recent advances in oral testosterone undecanoate formulations have introduced safer and more effective options. This review compares Jatenzo, Tlando, and Kyzatrex, highlighting their pharmacology, efficacy, safety, and clinical utility. Clinical trial data demonstrate restoration of eugonadal testosterone levels in most patients (80–88%), with shared risks including hypertension, polycythemia, and lipid changes. Differences in dosing regimens, titration requirements, and insurance coverage influence choice of therapy and patient adherence. Kyzatrex offers flexible titration and self-pay access, Tlando provides a fixed-dose regimen, and Jatenzo combines titratability with established clinical data. Collectively, these agents expand the therapeutic landscape of hypogonadism, offering effective, non-invasive alternatives that support individualized treatment strategies. Full article

Background: Due to the high frequency of pain associated with the masticatory system, in addition to the use of physiotherapy, it is sometimes beneficial to introduce percutaneous pharmacology. This is an example of a non-invasive alternative to the traditional route of administration, which can be highly effective and limit the risk of many side effects. The aim of this study is to evaluate the efficacy and safety of transdermal drug application by patients with temporomandibular disorders (TMD). Methods: A review of randomized controlled trials retrieved from PubMed, ACM, BASE, Scopus, Cochrane, and Google Scholar on 23 October 2025 was performed using the PRISMA Checklist. Studies that evaluated transdermal drug administration for masticatory system-related conditions were included. Trials involving interventions such as muscle punctures or any systemic treatments were excluded. The revised Cochrane tool (RoB 2) was used to assess the risk of bias. A statistical analysis of the effect of such therapy on pain and its influence on changes in mandibular abduction was performed. Results: A total of nine articles meeting the inclusion criteria were included, with a total of 390 participants. The risk of bias assessment indicated that most articles were of low risk of bias (6/8), while two were assessed as “some concerns”. The review found a significant reduction in pain on the visual analog scale (VAS) for selected active substances (p < 0.05). The greatest pain reduction occurred when 1.46% cannabidiol was used. There are few results regarding the effect of this method on jaw opening, and the results obtained are comparable for the placebo group, which was related to the application method. Conclusions: The results of this systematic review are promising and indicate the probable effectiveness of this method, but due to some limitations, this topic requires further investigation. Full article

Background/Objectives: Transdermal formulations are widely utilized in the pharmaceutical and cosmetic fields because they enable non-invasive administration and sustained local drug delivery. Conventional ex vivo skin permeation experiments using Franz diffusion cells have limitations in capturing the spatial and temporal dynamics of skin penetration. This study aimed to develop a confocal laser scanning microscopy (CLSM)-based approach to visualize and semi-quantitatively assess the penetration behavior of fluorescent dyes with differing lipophilicities. Methods: Four fluorescent dyes with different Log P values—Rhodamine B (Rho-B), Rhodamine 123 (Rho-123), Fluorescein Sodium (Flu-Na), and Nile Red (NR)—were formulated into lotion-based vehicles and applied to excised human abdominal skin. CLSM imaging was performed from 10 min to 240 min post-application. Fluorescence intensities were extracted from depth-resolved regions (R1–R4, 30-μm intervals) to examine penetration kinetics and distribution. Results: CLSM imaging demonstrated that Rho-B penetrated through stratum corneum and entered deep into the skin via the hair follicles. Rho-123 and Flu-Na exhibited intercellular and follicular penetration; however, Flu-Na showed only a slight increase in intensity over time; NR showed negligible penetration into the deeper layers. The results of our analysis indicated that moderately lipophilic substances such as Rho-B and Rho-123 diffused deeply into the skin via both transdermal and follicular routes, whereas highly hydrophobic or lipophilic substances remained in the superficial layers. Conclusions: The CLSM-based approach enabled spatially and temporally resolved, semi-quantitative evaluation of transdermal penetration in a single, non-destructive experiment. Although restricted to fluorescent probes, this approach provides a practical early-stage screening tool for comparing route-specific and time-dependent penetration behaviors of compounds with different lipophilicities. Full article