Search Results (143)

Transdermal drug delivery offers a non-invasive route for the systemic and localized administration of therapeutics; however, the skin’s barrier function limits its efficiency. This study investigates the application of various electromagnetic field (EMF) configurations to enhance the transdermal delivery of salicylic acid, a model compound with moderate lipophilicity and ionizability. Samples were exposed to pulsed, oscillating, static, and rotating magnetic fields, and their effects on physicochemical properties, thermal stability, skin permeation, and accumulation were evaluated. Structural analyses (FTIR, XRD) and thermal assessments (TGA, DSC) confirmed that EMF exposure did not alter the chemical structure or stability of salicylic acid. In vitro transdermal studies using porcine skin and Franz diffusion cells revealed that pulsed magnetic fields—especially with a 5 s on/5 s off cycle—and rotating magnetic fields at 30–50 Hz significantly enhanced drug permeation compared to controls. In contrast, static fields of negative polarity increased skin retention, suggesting their potential for controlled, localized delivery. These findings demonstrate that EMFs can be used as tunable, non-destructive tools to modulate drug transport across the skin and support their integration into transdermal delivery systems aimed at optimizing therapeutic profiles. Full article

Transdermal drug delivery systems (TDDSs) provide a non-invasive alternative to oral and parenteral routes, delivering drugs into the bloodstream while avoiding gastrointestinal degradation and first-pass metabolism. Despite benefits like enhanced bioavailability and patient compliance, the stratum corneum limits drug permeation. Ethosomes overcome the stratum corneum barrier with superior flexibility and permeability compared to liposomes. Ethanol disrupts the skin’s lipid bilayer, enabling deep penetration and efficient drug delivery. Ethosomes offer high entrapment efficiency and stability, delivering both hydrophilic and lipophilic drugs. However, challenges like stability optimization and clinical translation persist. This review examines the structural components, preparation methods, and therapeutic applications of ethosomes in metabolic and chronic diseases, including diabetes, cardiovascular diseases, neurodegenerative disorders, arthritis, and cancers. Moreover, it highlights the potential of ethosomes to revolutionize TDDSs for managing chronic and metabolic diseases, providing a foundation for further research and clinical development. Full article

Background: Influenza virus is one of the major respiratory virus infections that is a global health concern. Although there are already approved vaccines, most are administered via the intramuscular route, which is usually painful, leading to vaccine hesitancy. To this end, exploring the non-invasive, transdermal vaccination route using dissolving microneedles would significantly improve vaccine compliance. Research on innovative vaccine delivery systems, such as antigen-loaded PLGA microparticles, has the potential to pave the way for a broader range of vaccine candidates. Methods: In this proof-of-concept study, a combination of the inactivated influenza A H1N1 virus and inactivated influenza A H3N2 virus were encapsulated in a biodegradable poly (lactic-co-glycolic acid) (PLGA) polymeric matrix within microparticles, which enhanced antigen presentation. The antigen PLGA microparticles were prepared separately using a double emulsion (w/o/w), lyophilized, and characterized. Next, the vaccine microparticles were assessed in vitro in dendritic cells (DC 2.4) for immunogenicity. To explore pain-free transdermal vaccination, the vaccine microparticles were loaded into dissolving microneedles and administered in mice (n = 5). Results: Our vaccination study demonstrated that the microneedle-based vaccine elicited strong humoral responses as demonstrated by high antigen-specific IgA, IgG, IgG1, and IgG2a antibodies in serum samples and IgA in lung supernatant. Further, the vaccine also elicited a strong cellular response as evidenced by high levels of CD4+ and CD8a+ T cells in lymphoid organs such as the lymph nodes and spleen. Conclusion: The delivery of influenza vaccine-loaded PLGA microparticles using microneedles would be beneficial to individuals experiencing needle-phobia, as well as the geriatric and pediatric population. Full article

Recombinant human growth hormone (rhGH) is utilized in pediatric patients with short stature for a variety of indications, including those in which the primary growth defect is not related to growth hormone deficiency (GHD). However, due to the instability of the hormone in the gastrointestinal tract and its short half-life, an alternative route of administration is being sought, which may be the skin. One strategy to extend the half-life of proteins involves the use of biodegradable polymeric matrices for transdermal drug delivery systems. While hydrogels are recognized for their high stability, the transport of proteins through the skin may be hindered. To address this, the use of active carriers is being investigated to enhance the efficiency of protein permeation through the skin. In this study, an effort was made to optimize the concentration of phosphitin (PV) as a carrier for somatotropin (STH). PV is a protein that possesses a distinctive cation chelating capability and amphiphilic character. As the concentration of PV increased, the rate of its emulsifying activity increased concomitantly. Methylcellulose (MC) was used as the hydrogel matrix. The study investigated three distinct concentrations of PV to ascertain the most optimal concentration to enhance STH availability. Following the formulation of hydrogel compositions containing STH and PV, the permeation process through porcine skin was examined using Franz’s chambers. The findings revealed that the incorporation of PV significantly impacted both the penetration time of STH and the extent of STH penetration. Subsequently, an extensive evaluation of the physicochemical parameters of the formulations, encompassing pH, rheological, and textural properties, was conducted to assess their suitability for skin application. This evaluation aimed to ensure not only adequate persistence time of the formulation on the skin surface but also formulation stability and persistence of the active substance (STH). Full article

Nanoemulsions (NEs) have emerged as effective drug delivery systems over the past few decades due to their multifaceted nature, offering advantages such as enhanced bioavailability, protection of encapsulated compounds, and low toxicity. In the present review, we focus on advancements in drug delivery over the last five years across (trans)dermal, oral, ocular, nasal, and intra-articular administration routes using NEs. Rational selection of components, surface functionalization, incorporation of permeation enhancers, and functionalization with targeting moieties are explored for each route discussed. Additionally, apart from NEs, we explore NE-based drug delivery systems (e.g., NE-based gels) while highlighting emerging approaches such as vaccination and theranostic applications. The growing interest in NEs for drug delivery purposes is reflected in clinical trials, which are also discussed. By summarizing the latest advances, exploring new strategies, and identifying critical challenges, this review focuses on developments for efficient NE-based therapeutic approaches. Full article

Drugs administered by means of extravascular routes of drug administration must be absorbed into the systemic circulation, which involves the movement of the drug molecules across biological barriers such as epithelial cells that cover mucosal surfaces or the stratum corneum that covers the skin. Some drugs exhibit poor permeation across biological membranes or may experience excessive degradation during first-pass metabolism, which tends to limit their bioavailability. Various strategies have been used to improve drug bioavailability. Absorption enhancement strategies include the co-administration of chemical permeation enhancers, enzymes, and/or efflux transporter inhibitors, chemical changes, and specialized dosage form designs. Models with physiological relevance are needed to evaluate the efficacy of drug absorption enhancement techniques. Various in vitro cell culture models and ex vivo tissue models have been explored to evaluate and quantify the effectiveness of drug permeation enhancement strategies. This review deliberates on the use of in vitro and ex vivo models for the evaluation of drug permeation enhancement strategies for selected extravascular drug administration routes including the nasal, oromucosal, pulmonary, oral, rectal, and transdermal routes of drug administration. Full article

Nowadays, skin is one of the organs most commonly affected by diseases (infections, inflammations, and injuries) due to exposure to the external environment. Although topical treatment represents the most suitable administration route, it is poorly effective due to the low permeability of the drug through the skin. Skin drug delivery by lipid nanocarriers (LNs) appears to be a suitable therapeutic strategy to overcome these issues, allowing it to reach a topical or systemic effect. Several LN-based products have been developed to enhance the permeation of bioactive compounds through the skin, obtaining interesting results in both pharmaceutical and cosmetic fields. Therefore, this review aims to analyze the scientific literature regarding the use of LNs to treat major skin diseases (psoriasis, wound healing, atopic dermatitis, and acne) and esthetic skin defects (wrinkles and cellulite). Furthermore, attention has been paid to the transdermal application of LNs (topical formulations, transdermal patches, and microneedles), being a new topic in recent years. Full article

Nanosuspensions (NS), with their submicron particle sizes and unique physicochemical properties, provide a versatile solution for enhancing the administration of medications that are not highly soluble in water or lipids. This review highlights recent advancements, future prospects, and challenges in NS-based drug delivery, particularly for oral, ocular, transdermal, pulmonary, and parenteral routes. The conversion of oral NS into powders, pellets, granules, tablets, and capsules, and their incorporation into film dosage forms to address stability concerns is thoroughly reviewed. This article summarizes key stabilizers, polymers, surfactants, and excipients used in NS formulations, along with ongoing clinical trials and recent patents. Furthermore, a comprehensive analysis of various methods for NS preparation is provided. This article also explores various in vitro and in vivo characterization techniques, as well as scale-down technologies and bottom-up methods for NS preparation. Selected examples of commercial NS drug products are discussed. Rapid advances in the field of NS could resolve issues related to permeability-limited absorption and hepatic first-pass metabolism, offering promise for medications based on proteins and peptides. The evolution of novel stabilizers is essential to overcome the current limitations in NS formulations, enhancing their stability, bioavailability, targeting ability, and safety profile, which ultimately accelerates their clinical application and commercialization. Full article

Background/Objectives: Indomethacin (IDM) is commonly used to treat chronic inflammatory diseases such as rheumatoid arthritis and osteoarthritis. However, long-term oral IDM treatment can harm the gastrointestinal tract. This study presents a design for encapsulating IDM within mixed micelles (MMs)-loaded dissolving microneedles (DMNs) to improve and sustain transdermal drug delivery. Methods: Indomethacin-loaded mixed micelles (IDM-MMs) were prepared from Soluplus^® and Poloxamer F127 by means of a thin-film hydration method. The MMs-loaded DMNs were fabricated using a two-step molding method and evaluated for storage stability, insertion ability, in vitro release, in vitro transdermal penetration, and in vivo PK/PD studies. Results: The obtained MMs were stable at 4 °C and 30 °C for 60 days. The in vitro IDM transdermal penetration was remarkably improved by the MMs-loaded DMNs compared to a commercial patch. A pharmacokinetic study demonstrated that the MMs-loaded DMNs had a relative bioavailability of 4.1 in comparison with the commercial patch. Furthermore, the MMs-loaded DMNs showed a significantly shorter lag time than the commercial patch, as well as a more stable plasma concentration than the DMNs without MMs. The therapeutic efficacy of the IDM DMNs was examined in Complete Freund’s Adjuvant-induced arthritis mice. The IDM DMN treatment effectively reduced arthritis severity, resulting in decreased paw swelling, arthritis index, spleen hyperplasia, and serum IL-1β and TNF-α levels. Conclusions: Our findings demonstrated that the novel MMs-loaded DMNs were an effective strategy for sustained IDM release, providing an alternate route of anti-inflammatory drug delivery. Full article

Dermatoses are among the most prevalent non-fatal conditions worldwide. Given this context, it is imperative to introduce safe and effective dermatological treatments to address the diverse needs and concerns of individuals. Transdermal delivery technology offers a promising alternative compared to traditional administration methods such as oral or injection routes. Therefore, this review focuses on the recent achievements of nanocarrier-based transdermal delivery technology for dermatological therapy, which summarizes diverse delivery strategies to enhance skin penetration using various nanocarriers including vesicular nanocarriers, lipid-based nanocarriers, emulsion-based nanocarriers, and polymeric nanocarrier according to the pathogenesis of common dermatoses. The fundamentals of transdermal delivery including skin physiology structure and routes of penetration are introduced. Moreover, mechanisms to enhance skin penetration due to the utilization of nanocarriers such as skin hydration, system deformability, disruption of the stratum corneum, surface charge, and tunable particle size are outlined as well. Full article

Background: A woman’s entry into the menopause period is associated with a number of changes in the body, including those related to the immune system. Immune aging is a consequence of age-related changes in the function of immune cells and the composition of their subpopulations. Menopausal hormone therapy (MHT) is thought to partially neutralize the negative effects of aging on the immune system. Objective: We aimed to evaluate the effect of oral and transdermal MHT on cellular immunity parameters and cytokine profile in menopausal women. Methods: Fifty peri- and early postmenopausal women were included. Immune parameters were assessed by flow cytometry and multiplex analysis. Results: We showed that different routes of MHT administration led to significant changes in monocyte phenotype and a decrease in monocyte chemoattractant protein-1 (MCP-1) level in menopausal patients. In addition, oral MHT resulted in a significant increase in NK and B cells. A significant increase in the number of T-helper cells was observed with transdermal MHT. In addition, oral MHT resulted in a significant decrease in IL-1β level. Conclusions: We have demonstrated for the first time that oral therapy, in contrast to transdermal therapy, has a more pronounced effect on specific immune subpopulations of blood cells in menopausal women. This effect is likely to be responsible for its anti-aging properties in the context of immune aging as well as its protective effects in infectious diseases. Perhaps testing blood immune parameters or assessing immune status before prescribing MHT could become a routine step in clinical practice before choosing a patient management strategy. Full article

(1) Background: The escalating use of opioids contributes to social, health, and economic crises. In Spain, a notable surge in the medical prescription of opioids in recent years has been observed. The aim of this work was to assess the consumption rate of fentanyl, categorised by the different administration routes, in Primary Care in the province of Salamanca (Spain) spanning the years 2011 to 2022, and to compare it with the national trend and with data from the US. (2) Methods: Doses per inhabitant per day (DHD) were calculated, and interannual variations, as well as consumption rates, were subject to thorough analysis. (3) Results: The prevalence of fentanyl use in Salamanca has doubled from 1.21 DHD in 2011 to 2.56 DHD in 2022, with the transdermal system (TD) as the predominant administration route. This upward trajectory mirrors the national trend, yet the rise in fentanyl use is markedly lower than the reported data in the US. This finding may be attributed to an ageing population and potentially inappropriate fentanyl prescriptions, i.e., for the management of chronic non-cancer pain and other off-label prescriptions. (4) Conclusions: The use of fentanyl in Salamanca, particularly through transdermal systems, doubled from 2011 to 2022, aligning with the national trend. Preventive measures are imperative to prevent fentanyl misuse and moderate the observed escalation in consumption rates. Full article

Essential oils (EOs) are concentrated, hydrophobic volatile compounds derived from different parts of plants. They are recognized for their diverse and versatile functional properties. Approximately 90% of EOs are administered via topical or transdermal routes. However, EOs are susceptible to oxidation, and their high volatility often poses a challenge to the transdermal delivery of their bioactive constituents. Additionally, the direct application of pure EOs on the skin may result in irritating effects. Hence, various novel carrier systems have been explored for the topical application of EOs. Among these, nanoemulgel has received particular attention from the cosmeceutical industry. It is a hybrid technology combining nanoemulsion and a gelling phase, which can enhance the bioadhesivity of EOs, at the same time minimizing their irritating effects. This review summarizes the methods of EO extraction, steps and factors influencing the preparation of EO nanoemulgel, and characterization parameters for nanoemulgel studies. The potential cosmeceutical applications of EO nanoemulgels as an anti-inflammatory, antimicrobial, antioxidant, and penetration enhancer are also compiled and discussed. Full article

The ability to precisely treat human disease is facilitated by the sophisticated design of pharmacologic agents. Nanotechnology has emerged as a valuable approach to creating vehicles that can specifically target organ systems, effectively traverse epithelial barriers, and protect agents from premature degradation. In this review, we discuss the molecular basis for epithelial barrier function, focusing on tight junctions, and describe different pathways that drugs can use to cross barrier-forming tissue, including the paracellular route and transcytosis. Unique features of drug delivery applied to different organ systems are addressed: transdermal, ocular, pulmonary, and oral delivery. We also discuss how design elements of different nanoscale systems, such as composition and nanostructured architecture, can be used to specifically enhance transepithelial delivery. The ability to tailor nanoscale drug delivery vehicles to leverage epithelial barrier biology is an emerging theme in the pursuit of facilitating the efficacious delivery of pharmacologic agents. Full article

Skin is the largest organ and a multifunctional interface between the body and its environment. It acts as a barrier against cold, heat, injuries, infections, chemicals, radiations or other exogeneous factors, and it is also known as the mirror of the soul. The skin is involved in body temperature regulation by the storage of fat and water. It is an interesting tissue in regard to the local and transdermal application of active ingredients for prevention or treatment of pathological conditions. Topical and transdermal delivery is an emerging route of drug and cosmetic administration. It is beneficial for avoiding side effects and rapid metabolism. Many pharmaceutical, technological and cosmetic innovations have been described and patented recently in the field. In this review, the main features of skin morphology and physiology are presented and are being followed by the description of classical and novel nanoparticulate dermal and transdermal drug formulations. The biophysical aspects of the penetration of drugs and cosmetics into or across the dermal barrier and their investigation in diffusion chambers, skin-on-a-chip devices, high-throughput measuring systems or with advanced analytical techniques are also shown. The current knowledge about mathematical modeling of skin penetration and the future perspectives are briefly discussed in the end, all also involving nanoparticulated systems. Full article