Search Results (571)

Phytochemicals have attracted considerable attention as therapeutically relevant bioactive compounds due to their diverse pharmacological activities, including anti-inflammatory, antioxidant, anticancer, and metabolic regulatory effects. However, their clinical translation is frequently hindered by unfavorable pharmaceutical properties such as poor aqueous solubility, chemical instability, rapid metabolism, and limited bioavailability. These challenges have constrained the reproducibility and therapeutic reliability of phytochemical-based interventions. In this context, nanotechnology-enabled delivery systems have emerged as effective strategies to overcome the intrinsic limitations of phytochemicals and enhance their biological performance. This review provides a comprehensive overview of recent advances in nanotechnology-based delivery platforms for phytochemicals, with emphasis on lipid-based nanocarriers, polymeric nanoparticles, nanoemulsions and self-nanoemulsifying drug delivery systems, inorganic and hybrid nanocarriers, as well as hydrogel-based and transdermal delivery systems. We discuss how rational nanocarrier design improves solubility, stability, pharmacokinetics, cellular uptake, and tissue targeting, thereby enhancing therapeutic efficacy across multiple disease areas. In addition, critical safety, toxicity, manufacturing, and regulatory considerations that influence translational potential are addressed. By adopting a delivery-centered perspective, this review highlights current challenges and future opportunities in nano-phytomedicine and underscores the importance of integrating nanotechnology, biological insight, and regulatory-conscious development to advance phytochemicals toward clinically viable therapeutic applications. Full article

The perception that hormonal contraception causes weight gain is a general belief that frequently hinders the initiation and continuation of effective family planning. This narrative review analyses data from Cochrane systematic reviews and recent pharmacogenomic studies to separate patient perception from metabolic reality. Analysis of high-quality data, including Cochrane systematic reviews, indicates that the association between Combined Hormonal Contraceptives (CHCs)—including oral pills, the transdermal patch, and the vaginal ring—and weight gain is not supported by consistent high-quality evidence. Placebo-controlled trials demonstrate that these methods are weight-neutral on average. Perceived weight increases in CHC users are likely mediated in part by fluid retention linked to the estrogenic stimulation of the Renin–Angiotensin–Aldosterone System (RAAS), rather than adipose tissue accumulation. Conversely, Depot Medroxyprogesterone Acetate (DMPA) represents a verified clinical risk for weight gain, showing a demonstrated clinical association with significant fat mass accumulation. Hypothesized biological mechanisms for this increase include hypothalamic appetite stimulation and glucocorticoid-like activity. The etonogestrel implant occupies a complex middle ground. While population-level data suggests weight neutrality, recent exploratory pharmacogenomic research has identified a specific variant in the Estrogen Receptor 1 (ESR1) gene. For the minority of women carrying this variant, the implant may trigger clinically significant weight gain, suggesting a biological basis for their subjective experience despite statistical evidence. Ultimately, the persistence of the weight gain concern is fueled by the nocebo effect and the misattribution of natural age-related weight trajectories to contraceptive use. Full article

The human skin, specifically the stratum corneum (SC), remains a formidable barrier to the delivery of therapeutic agents. Nearly 80% of new drug candidates exhibit poor solubility or low permeability, necessitating the development of novel delivery vehicles. Therapeutic deep eutectic solvents (TheDES) have emerged as a “green,” multifunctional solution capable of significantly enhancing the solubility and transdermal flux of active pharmaceutical ingredients (APIs). This review discusses the physicochemical fundamentals of TheDES, mechanisms of permeation enhancement—including the newly identified “lipid exchange” effect—and the transition from liquid solvents to advanced dosage forms such as eutectogels and nanoemulsions. Current therapeutic applications in pain management, infectious diseases, and chronic conditions are highlighted, alongside critical assessments of dermatological safety and future directions in computational modeling. 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

This work introduces a new mathematical model designed to describe the glucose–insulin dynamics associated with a glucose-responsive smart microneedle patch reported in the literature. The model captures the complete sequence of the patch behavior, from detecting glucose changes to controlled transdermal insulin delivery and gradually restoring blood glucose levels to the normal range. Our simulations show that the patch can effectively manage glucose not only during fasting conditions but also after single and multiple meals, restoring glucose levels to healthy levels within a short period. The model predictions are consistent with experimentally reported trends in previously published studies, which strengthens confidence in the biological realism of the proposed mechanism. Because some parameters in such systems are difficult to measure directly, we also performed a comprehensive sensitivity analysis to understand how variations in key parameters influence system stability. The results highlight the central role of the insulin release rate and the five glucose–regulation parameters examined in the sensitivity analysis, providing clear guidance on the most critical aspects of patch design for reliable performance. Overall, this study provides a simplified yet robust mathematical framework that makes the behavior of a glucose-responsive microneedle patch easy to understand and analyze. It lays the groundwork for future refinement of control strategies and optimization of patch design, improving control strategies, and developing more advanced systems that can maintain healthy glucose levels naturally and intuitively. Full article

Background/Objectives: Skin aging and wrinkle formation are primarily driven by ultraviolet (UV)-induced oxidative stress and inflammation. Resveratrol (RSV) and nicotinamide (NCT) possess potent anti-aging properties but suffer from poor skin penetration. This study aimed to develop an advanced transdermal delivery system incorporating RSV/NCT-loaded cerosomes within poly(lactic-co-glycolic acid) (PLGA) microneedles to enhance skin permeation and anti-aging performance. Methods: RSV/NCT-loaded cerosomes were formulated using thin-film hydration of phosphatidylcholine, ceramides (III, IIIB, and VI), and poloxamer surfactants, subsequently optimized via a D-optimal mixture design. PLGA microneedles with optimized cerosomes were tested for their mechanical strength, penetration, drug loading, and release. Ex vivo permeation and in vivo evaluations were performed using a UVA-induced skin wrinkling model. Results: Optimized cerosomes exhibited high entrapment efficiency for RSV and NCT (91 ± 0.56% and 85 ± 0.56%, respectively), nanoscale size (195 ± 0.78 nm), low polydispersity (0.23 ± 0.01), and a negative zeta potential (−22 ± 0.45 mV). PLGA microneedles exhibited sufficient mechanical integrity and effective penetrability through Parafilm^® layers. Microneedle-loaded cerosomes enabled sustained drug release (approximately 65–70% over 48 h) and enhanced ex vivo permeation, approximately for NCT and RSV (1450 μg/cm² and 1000 μg/cm², respectively). In vivo investigations revealed improved skin appearance, restoration of epidermal thickness and collagen architecture, reduced levels of inflammatory cytokines (TNF-α, IL-1β, IL-6, NLRP3), reduced oxidative stress biomarkers (GSH, GPx, MDA, SOD), and genetic upregulation of VEGF, TGF-β1, and β-Catenin. Conclusions: The RSV/NCT cerosome-encapsulated PLGA microneedle system offers a promising, minimally invasive approach with superior transdermal delivery, sustained efficacy, and significant anti-aging benefits. Full article

This review summarizes scientific advances about the sonochemical synthesis of starch nanoparticles (St-NPs) for the food industry, as well as nutraceutical and drug delivery applications. High-intensity ultrasonication (HIU) has been explored as a versatile and environmentally friendly alternative to conventional methods for synthesizing St-NPs with high yields (>90%), controlled size (~100 nm), and minimal effluent generation. Thus, HIU has been explored (pre- or post-treatment) to mitigate the inherent disadvantages (high-cost, low yields, and environmental impact) of hydrothermal gelatinization, acid/alkaline hydrolysis, enzymatic hydrolysis, enzyme branching, water-in-oil and oil-in-water emulsions, non-solvent nanoprecipitation, extrusion, high-pressure homogenization, high-energy milling, and cold plasma. Conventional sources of starch (corn [normal, waxy, high-amylose] and potato) and other unconventional sources (tubers [cassava, yam, malanga], seeds and grains [sorghum, barley, quinoa, lotus], breadfruit, pinhao seed, Araucaria angustifolia) have been subjected to single or assisted sonochemical protocols to obtain St-NPS with unique structural, physicochemical, and technological properties. The physical–mechanical effects of ultrasonication (cavitation, heat, and pressure) directly promote surface functionalization (i.e., esterification, pore formation) and impact the St-NPS’s particle size, double-helix structure, enzymatic-resistance properties, crystallinity, and intra- and intermolecular arrangements. Pickering additives in food systems, colloids in beverages, nanocomposites in biofilms for food packaging, and nanocarriers for drug and nutraceutical delivery (oral and transdermal) have been the most reported applications. Full article

Insulin injection remains the best therapy for diabetes mellitus, but subcutaneous injection continues to pose challenges, including patient discomfort, poor compliance and fluctuating plasma glucose profiles. Recently, transdermal insulin delivery has emerged as a non-invasive strategy that bypasses gastrointestinal degradation and first-pass hepatic metabolism, thereby increasing insulin bioavailability and enhancing patient acceptance. Recent developments in nanomedicine have facilitated the development of transdermal patches with enhanced drug encapsulation, uptake and controlled release. Nanostructured lipid carriers, polymeric nanocomposites, liposomes and SLNs have demonstrated a five-fold enhancement of transdermal flux and an extended insulin effect in preclinical models. The addition of ionic liquids and polymeric nanogels leads to an additional increase in insulin aqueous solubility and permeation, resulting from the temporary regulation of stratum corneum lipid organization. Bright and stimuli-responsive patches with glucose oxidase or phenylboronic acid functional groups enable regulated insulin delivery in response to changes in blood glucose, demonstrating near-normoglycemia for up to 48 h in animal testing. Nanocomposite systems assisted by microneedles have also been advanced to the early clinical phase, offering enhanced reproducibility of their pharmacokinetics and a low risk of dermal irritation. Despite these encouraging results, several translational challenges remain, such as biocompatibility, repeatability in the production of nanocarriers, long-term stability of formulations and regulatory standardization. This review examines the physicochemical design principles, materials innovations and permeation mechanism of nanomedicine-engineered insulin patches, the current state of preclinical and clinical advancements, challenges in production and future perspectives in viable patient-focused transdermal insulin delivery. Full article

Microneedles are a pediatric-friendly drug delivery system that has attracted many novel research endeavors. The fact that it creates a tiny cavity in the epidermis, which can allow peptides, proteins, nucleotides, and other large-sized molecules to penetrate the skin barrier, is very advantageous for transdermal delivery. In this review article, we shed light on several pediatric applications of microneedles, such as the delivery of proteins, vaccines, and diagnostics. We believe the advantages of microneedles will continue to expand and be applied to other sites in the body. Full article

Analytical models of transdermal drug delivery (TDD) often represent deeper skin layers using ideal sink assumptions or phenomenological interfacial resistances. While mathematically convenient, these approaches obscure the physical role of the dermis and hypodermis in controlling molecular transport. Here, we develop an impedance-based analytical model for diffusion across multilayer skin membranes, in which the epidermal barrier is dynamically coupled to a finite diffusive backing layer representing the dermis–hypodermis composite. Diffusion impedance links transport conductivity, storage capacity, and layer thickness, while preserving continuity of concentration and flux at all interfaces. Closed-form expressions in the Laplace domain describe concentration fields and interfacial fluxes, and cumulative drug uptake is computed in the time domain via inverse Laplace transformation. The model identifies distinct short- and long-time transport regimes. Commonly used Dirichlet and Robin boundary conditions emerge as limiting cases but cannot reproduce the regime-dependent behavior of a backing layer. In particular, Robin formulations reduce the backing layer to a constant effective resistance, neglecting its storage capacity and time-dependent impedance. By replacing ad hoc boundary conditions with a physically grounded impedance framework, this approach provides a unified and extensible method for analyzing multilayer transport systems, including extensions to anomalous or memory-dependent diffusion. 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

This study developed a transdermal drug delivery system for Rheumatoid Arthritis (RA) using a dual-network hydrogel microneedle patch loaded with methotrexate nanocrystals (DHMN@MTX-NCs), and explored its synergistic therapy with Adalimumab (ADA) for a painless, long-acting, and targeted RA treatment. This study synthesized Methacrylated Hyaluronic Acid and Methacrylated Gelatin. MTX-NCs were prepared by solvent-antisolvent precipitation and incorporated into a dual-network hydrogel microneedle patch via centrifugal molding. Evaluations included pharmaceutical properties, mechanical strength, drug release, in vitro anti-inflammatory effects on RAW 264.7 cells, and therapeutic efficacy in a rat RA model. The experimental results show that the prepared MTX-NCs present a spherical shape, an average size of 325.72 nm, a PDI of 0.154, and a drug-loading capacity of 61.3%. The microneedle patch exhibited high puncture efficiency and suitable swelling. In vitro, DHMN@MTX-NCs combined with ADA most strongly inhibited macrophage migration, upregulated IL-10, and downregulated TNF-α, IL-1β, NO, iNOS, and COX-2. In vivo, both monotherapy and combination therapy reduced joint swelling, bone erosion, and histopathological damage. Ultimately, the study demonstrated the synergistic anti-inflammatory efficacy of DHMN@MTX-NCs combined with ADA, providing a novel, non-invasive, and targeted therapeutic strategy for RA. Full article

Background/Objectives: Cannabinoids are increasingly recognised for their therapeutic potential beyond well-established indications such as chronic pain, multiple sclerosis, and specific epileptic syndromes. Recent advances have highlighted their possible role in less-common or orphan diseases, opening new avenues for pharmaceutical research and clinical application. Methods: This review provides a critical synthesis of the most recent evidence (2020–2025), available in PubMed and Scopus, regarding the use of cannabinoids in conditions including refractory epilepsies beyond Dravet and Lennox–Gastaut syndromes, movement disorders such as dystonia and Tourette syndrome, rare dermatological diseases like epidermolysis bullosa, and emerging data in Crohn’s disease. Results: Negative outcomes, such as those reported in Fragile X syndrome trials, are also discussed as instructive examples of methodological and pharmacological challenges. Particular attention is given to the optimisation of pharmaceutical formulations and advanced separation technologies, including oromucosal sprays, transdermal gels, and novel nanocarrier systems, which aim to overcome issues of bioavailability and variability in patient response. Finally, safety concerns, regulatory aspects, and the need for robust clinical trials are addressed. Conclusions: Overall, cannabinoids represent a promising yet underexplored therapeutic option in rare and complex disorders, warranting further investigation supported by innovative pharmaceutical approaches. Full article

ILs have emerged as versatile formulation components in DDS due to their tunable physicochemical properties and ability to modulate biomolecular and interfacial interactions. This review examines IL-enabled DDS strategies across major delivery platforms, including nanocarrier-based systems, microtechnology-assisted devices, and biomacromolecule formulations, with emphasis on formulation design principles rather than administration route. We discuss how ILs enhance API solubility, stability, permeability, and formulation flexibility through API–IL complex formation and controlled membrane interactions and relate mechanistic insights into IL–membrane interactions to both delivery performance and safety via structure–activity relationships. Current limitations, including toxicity concerns, lack of standardized evaluation criteria, scalability challenges, and regulatory ambiguity, are critically assessed. Overall, this review positions ILs as formulation-enabling materials rather than standalone therapeutics and underscores the importance of rational design, standardized assessment, and early regulatory alignment for advancing IL-enabled DDS toward clinical translation. Full article

Background/Objectives: Nanoemulsions (NEs) are a promising platform for transdermal drug delivery (TDD); however, how the polarity of the active pharmaceutical ingredient (API) influences NE structure–performance relationships remains insufficiently understood. This study aimed to systematically compare the transdermal delivery behavior of a hydrophilic API, salbutamol hemisulphate (log P ≈ 0.1), and a lipophilic API, ibuprofen (log P ≈ 3.3), incorporated into compositionally matched nanoemulsion systems. Methods: Kolliphor EL–based NEs were prepared using identical excipients, with systematic variation of oil, surfactant, and water ratios. Thirty-six formulations were produced for each API. Physical stability, droplet size, and viscosity were characterized, and in vitro skin permeation studies were conducted using excised mouse skin. Flux and cumulative permeation were quantified, and statistical analyses were performed to identify key compositional drivers of permeation. Results: Ibuprofen-containing NEs exhibited superior physical stability compared to salbutamol formulations, likely due to interfacial interactions that imparted surfactant-like behavior. Both APIs formed nanoscale droplets, with salbutamol formulations ranging from 16 to 507 nm and ibuprofen formulations spanning 12–563 nm, more frequently yielding sub-100 nm droplets. Viscosity values covered broad ranges (3–9532 mPa·s for salbutamol; 13.4–9759 mPa·s for ibuprofen), with salbutamol generating an extended high-viscosity domain at 50% (w/w) surfactant and ibuprofen showing a narrower viscosity maximum at 30–40% surfactant. Salbutamol NEs achieved high fluxes (up to 374 µg/cm²·h) and cumulative permeation of approximately 80% of the applied dose, whereas ibuprofen formulations showed markedly lower fluxes (maximum 32 µg/cm²·h) and cumulative permeation below 6%. High surfactant levels suppressed permeation for both APIs, but the dominant positive drivers differed: balanced oil–water ratios for salbutamol and hydration-dependent diffusional resistance for ibuprofen. Conclusions: These findings demonstrate that API polarity and interfacial portioning behavior decisively govern NE performance, providing a framework for rational tailoring of oil–surfactant–water ratios to maximize transdermal delivery efficiency. Full article