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[Display omitted] Hydrogel microneedle patches have emerged as promising platforms for painless, minimally invasive, safe, and portable transdermal drug administration. However, the conventional mold-based fabrication processes and inherent single-functionality of such microneedles present significant hurdles to broader implementation. Herein, we have developed a novel approach utilizing a precursor solution of robust nanocomposite hydrogels to formulate photo-printable inks suitable for the direct 3D printing of high-precision, triple-responsive hydrogel microneedle patches through digital light processing (DLP) technology. The ink formulation comprises four functionally diverse monomers including 2-(dimethylamino)ethyl methacrylate, N -isopropylacrylamide, acrylic acid, and acrylamide, which were crosslinked by aluminum hydroxide nanoparticles (AH NPs) acting as both reinforcing agents and crosslinking centers. This results in the formation of a nanocomposite hydrogel characterized by exceptional mechanical strength, an essential attribute for the 3D printing of hydrogel microneeedle patches. Furthermore, this innovative 3D printing strategy facilitates facile customization of microneedle geometry and patch dimensions. As a proof-of-concept, we employed the fabricated hydrogel microneedles for transdermal delivery of bovine serum albumin (BSA). Importantly, these hydrogel microneedles displayed no cytotoxic effects and exhibited triple sensitivity to pH, temperature and glucose levels, thereby enabling more precise on-demand drug delivery. This study provides a universal method for the rapid fabrication of hydrogel microneedles with smart responsiveness for transdermal drug delivery applications. [ABSTRACT FROM AUTHOR]

The human skin is a readily accessibl esurface for drug delivery. Skin of an average adult body covers a surface of approximately 2m2 and receives about one-third of the blood circulating through the body. Over the past decades, developing controlled drug delivery as become increasingly important in the pharmaceutical industry. The human skin surface is known to contain, on anaverage, 10-70 hair follicles and 200-250 sweat ducts on every square centimeters of the skin area. It is one of the most readily accessibl eorgans of the human body. There is considerable interest in the skin as a site of drug application both for local and systemic effect. However, thes kin, in particular the stratum corneum, poses a formid able barrier drug penetration there by limiting topical and Transdermal bioavailability. Skin penetration enhancement techniques have been devel oped to improve bioavailability and increase the range of drugs for which topical and Transdermal delivery syste(NDDS). [ABSTRACT FROM AUTHOR]

A 54-year-old woman presents with low libido, diminished arousal, and anorgasmia. She had undergone a hysterectomy and bilateral salpingo-oophorectomy at 49 years of age owing to menorrhagia and a family history of ovarian cancer. She has been using transdermal estradiol patches and topical vaginal estradiol and has no meno-pausal symptoms or dyspareunia. She is in a loving relationship with no major life stressors, does not have depression, and takes no other medication. All other clinical characteristics, including her weight and blood pressure, are normal. She has recently become aware that there may be treatment options for low libido and would like to discuss these with you. How would you respond? [ABSTRACT FROM AUTHOR]

Background: Chronic pain significantly impacts quality of life and poses substantial public health challenges. Buprenorphine, a synthetic analog of thebaine, is recognized for its potential in managing moderate to severe chronic pain with fewer side effects and a lower incidence of tolerance compared to traditional opioids. Objective: This retrospective study aimed to assess the long-term efficacy and safety of buprenorphine transdermal patches in patients with moderate and severe chronic pain, with a focus on pain relief sustainability and tolerance development. Methods: This retrospective observational study involved 246 patients prescribed buprenorphine transdermal patches. We evaluated changes in pain intensity using the Numeric Rating Scale (NRS), assessed opioid tolerance based on FDA guidelines for morphine-equivalent doses, and measured patientreported outcomes through the Patients' Global Impression of Change (PGIC). Any adverse events were also recorded. Results: Over the 36-month period, there was a significant reduction in NRS scores for both moderate and severe pain patients, demonstrating buprenorphine's sustained analgesic effect. Tolerance measurement indicated that no patients required increases in morphine-equivalent doses that would meet or exceed the FDA's threshold for opioid tolerance (60 mg/day of morphine or equivalent). Additionally, patient satisfaction was high, with the PGIC reflecting significant improvements in pain management and overall wellbeing. The side effects were minimal, with skin reactions and nausea being the most commonly reported but manageable adverse events. Conclusion: The study findings validate the long-term use of buprenorphine transdermal patches as an effective and safe option for chronic pain management, maintaining efficacy without significant tolerance development. These results support the continued and expanded use of buprenorphine in clinical settings, emphasizing its role in reducing the burdens of chronic pain and opioid-related side effects. Further research is encouraged to refine pain management protocols and explore buprenorphine's full potential in diverse patient populations. [ABSTRACT FROM AUTHOR]

(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. [ABSTRACT FROM AUTHOR]

AbstractIn this study, in-vitro release experiments were performed using a Franz Diffusion Cell system for Terbinafine Hydrochloride, which is used in the treatment of various fungal infections in the skin caused by many susceptible dermatophytes. In order to evaluate TH transdermally, it was aimed to compare the permeability between polymeric membranes synthesized with polyvinyl alcohol and chitosan mixtures and commercial membranes. In the transdermal drug delivery system calculations, the Fick Diffusion Law was modified and the obtained data were compared. The study was evaluated according to the USP <1724> topical drug products in semisolid form - performance tests. A new high-performance liquid chromatography method was validated for the assay of TH released into the receptor medium in accordance with the ICH guideline. According to the results obtained during the validation process, the limit of detection value was calculated as 0.005 µg/mL and the limit of quantification value was 0.013 µg/mL. Since polymer-based synthetic membranes provide permeability according to molecular size, properties and the ideal environment for measuring and analyzing the diffusion rate of a compound, in experiments conducted using membranes of different structures, the permeability profiles of selected polymer synthetic membranes were statistically evaluated. It has been noted that the hydroxyl groups in PVA and the hydrophilic CS-g-PNDMAAm graft copolymer act at varying rates to enhance or reduce the permeability across the membrane by promoting its diffusion. NaY zeolite has been shown to function as an adsorbent against the medication, lessening the impact of hydrophilic PVA without supplying permeability. [ABSTRACT FROM AUTHOR]

Berberine is an isoquinolone alkaloid present in a wide variety of plants. Other than Type 2 diabetes and hypertension it is also found to have an effect in lowering blood cholesterol levels. However, because of its poor oral bioavailability and substantial first pass hepatic metabolism it is consumed in higher dosage leading to side effects. To reduce dosage and avoid adverse effects, transdermal delivery is investigated using transethosomal gel as a carrier. Transethosomes are ethanolic nanocarriers that are specifically designed for the dermal or transdermal delivery route as it has enhanced permeation of the vesicles. In our study we have successfully investigated the potential use of berberine loaded transethosomal gel (BBR-TE) as a carrier for transdermal delivery. Three-level three-factorial Box Behnken Design was used to optimize BBR-TE (Opt-BBR-TE). The optimized formulation was further evaluated and found to have a particle size of 165.70 nm with entrapment efficiency of 79.60±4.07%. The in vitro drug release study suggested the non-Fickian transport mechanism. The ex vivo skin permeation was found to be 94.35±3.64% when compared to berberine conventional formulation. Berberine has also shown promising antioxidant activity when compared to the standard solution and was entrapped inside TE vesicles in non-crystalline form. The Opt-BBR-TE was converted into gel form. Various parameters of the gel such as pH, Drug Content, Spreadability and extrudability were found to have promising results. Present study data revealed that the developed transethosomal gel formulation was found to be a potentially useful drug carrier for transdermal delivery of berberine. [ABSTRACT FROM AUTHOR]

This document is an editorial from the journal Pharmaceutics, which celebrates its 15th anniversary and highlights advancements in process and formulation modeling in the pharmaceutical industry. The editorial emphasizes the significance of modeling in product development and discusses different types of models available to scientists and engineers. It also provides a summary of the articles included in a special issue of the journal, covering topics such as nanosuspensions, computational techniques, laser ablation, and wet granulation. The editorial concludes by summarizing the main findings from each contribution in the special issue. These studies offer valuable insights into improving drug delivery efficiency and enhancing pharmaceutical manufacturing processes. [Extracted from the article]

Compared to other forms of drug administration, the use of Transdermal Drug Delivery Systems (TDDSs) offers significant advantages, including uniform drug release profiles that contribute to lower side effects and higher tolerability, avoidance of direct exposure to the gastrointestinal tract, better patient compliance due to their non-invasive means of application and others. Mesoporous silica membranes are of particular interest in this regard, due to their chemical stability and their tunable porous system, with adjustable pore sizes, pore volumes and surface chemistries. While this allows for fine-tuning and, thus, the development of optimized TDDSs with high loading capacities and the desired release profile of a given drug, its systemic availability also relies on skin penetration. In this paper, using a TDDS based on mesoporous silica membranes in Franz cell experiments on porcine skin, we demonstrate surprisingly substantial drug loss during skin penetration. Drug passage through porcine skin was found to be dependent on the age and pre-treatment of the skin. pH and temperature were major determinants of drug recovery rates as well, indicating drug loss in the skin by enzymatic metabolization. Regarding the TDDS, higher loading obtained by SO3H surface modification of the mesoporous silica membranes reduced drug loss. Still, high loss rates in the skin were determined for different drugs, including anastrozole, xylazine and imiquimod. We conclude that, beyond the fine-tuned drug release profiles from the mesoporous silica membrane TDDS, remarkably high drug loss in the skin is a major issue for achieving desired skin penetration and, thus, the systemic availability of drugs. This also poses critical requirements for defining an optimal TDDS based on mesoporous silica membranes. [ABSTRACT FROM AUTHOR]

Highlights The woven lattice sandwich composites (WLSCs) are susceptible to damage during service, which leads to a decline in their mechanical properties. Therefore, it is crucial to develop repair methods that specifically target the mechanical properties of WLSCs. In this study, repair techniques for the common types of skin and core damage in WLSCs were propose. The repair process begins with identifying the type of structural damage and removing the damaged section. Subsequently, the skin and core layers are repaired accordingly. The mechanical properties before and after repair are then compared through experimental evaluations. The results demonstrate that the carrying capacity of the repaired WLSCs is 85% higher than that of the original, unrepaired structure using the selected repair method. Typical damage modes of woven lattice sandwich composites were classified. Repairing methods are proposed for woven lattice panels based on damage modes. Core‐foaming and skin patch adhering perfectly rehabilitate the damaged sandwich. Bearing capacity of the repaired sandwich slightly surpasses its original structure. [ABSTRACT FROM AUTHOR]

The stratum corneum layer of skin poses a major barrier for transdermal drug delivery. Recently, nanocarriers and microneedles fabricated from renewable polymers have emerged as promising platforms to enhance permeation across this barrier. This letter highlights recent progress in using biocompatible nanocarriers and microneedle arrays to improve transdermal drug delivery. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD), affecting about ten million people globally, presents a significant health challenge. Rotigotine (RTG), a dopamine agonist, is currently administered as a transdermal patch (Neupro®) for PD treatment, but the daily application can be burdensome and cause skin irritation. This study introduces a combinatorial approach of dissolving microarray patch (MAP) and nanosuspension (NS) for the transdermal delivery of RTG, offering an alternative to Neupro®. The RTG-NS was formulated using a miniaturized media milling method, resulting in a nano-formulation with a mean particle size of 274.09 ± 7.43 nm, a PDI of 0.17 ± 0.04 and a zeta potential of −15.24 ± 2.86 mV. The in vitro dissolution study revealed an enhanced dissolution rate of the RTG-NS in comparison to the coarse RTG powder, under sink condition. The RTG-NS MAPs, containing a drug layer and a 'drug-free' supporting baseplate, have a drug content of 3.06 ± 0.15 mg/0.5 cm2 and demonstrated greater amount of drug delivered per unit area (∼0.52 mg/0.5 cm2) than Neupro® (∼0.20 mg/1 cm2) in an ex vivo Franz cell study using full-thickness neonatal porcine skin. The in vivo pharmacokinetic studies demonstrated that RTG-NS MAPs, though smaller (2 cm2 for dissolving MAPs and 6 cm2 for Neupro®), delivered drug levels comparable to Neupro®, indicating higher efficiency per unit area. This could potentially avoid unnecessarily high plasma levels after the next dose at 24 h, highlighting the benefits of dissolving MAPs over conventional transdermal patches in PD treatment. [Display omitted] • An alternative approach to deliver rotigotine via microarray patch was introduced. • Dose per unit area can be improved by using such approach in comparison to Neupro®. • A single 24 h application can provide therapeutic rotigotine levels to at least 2 days. • Unnecessarily high rotigotine plasma level may be avoided by using such approach. [ABSTRACT FROM AUTHOR]

Controllable and long‐term release remains a great challenge in current drug delivery systems. Benefiting from their efficient drug loading and painless administration, microneedles (MNs) have emerged as a promising platform for transdermal drug delivery, while they often fail to achieve long‐term tissue adhesion and controllable extended drug release. Here, 3D printing of an innovative MN patch is presented with succulent‐inspired responsive microstructures and light‐controllable long‐term release capability. The MN exhibits a reversible shrink‐swell volume change behavior in response to surrounding humidity, which enables sufficient mechanical strength for skin penetration under the shrinkage conditions and efficient long‐term adhesion when swollen in skin tissues. Moreover, the MN patch introduces a controllable long‐term drug release system, achieved through the integration of thiolated heparin (Hep‐SH) for sustained growth factor release and graphene oxide (GO) nanosheets for controlled drug release via near infrared (NIR) laser irradiation. The MN patches with growth factor loading have good biocompatibility and can promote the proliferation, migration, and proangiogenesis of endothelial cells is further demonstrated. Thus, it is believed that such flexible MN patches can be promising candidates for controllable long‐term transdermal drug delivery as well as other related tissue engineering applications. [ABSTRACT FROM AUTHOR]

Background: Hyposalivation is treated using oral cholinergic drugs; however, systemic side effects occasionally lead to discontinuation of treatment. We aimed to investigate the effects of transdermal pilocarpine on the salivary gland skin on saliva secretion and safety in rats. Methods: Pilocarpine was administered to rats orally (0.5 mg/kg) or topically on the salivary gland skin (5 mg/body). Saliva volume, the number of sweat dots, and fecal weight were measured along with pilocarpine concentration in plasma and submandibular gland tissues. Results: Saliva volume significantly increased 0.5 h after oral administration and 0.5, 3, and 12 h after topical administration. Fecal weight and sweat dots increased significantly 1 h after oral administration; however, no changes were observed after topical application. The pilocarpine concentration in the submandibular gland tissues of the topical group was higher than that in the oral group at 0.5, 3, and 12 h of administration. Conclusions: Pilocarpine application to salivary gland skin persistently increased salivary volume in rats without inducing sweating or diarrhea. Transdermal pilocarpine applied to the skin over the salivary glands may be an effective and safe treatment option for hyposalivation. [ABSTRACT FROM AUTHOR]

Nowadays, transdermal drug delivery system (TDDS) has been developed continuously because it solves the problem of drug level inconsistencies in the blood and prevents the drug from being destroyed in the digestive tract. However, the limitations of TDDS are the low release rate of the patch and difficult penetration of the drug to the skin. Therefore, this research aims to study drug release behavior of aspirin with and without applied electrical potential for controlled drug release from the pullulan hydrogel patch using sodium trimetaphosphate and citric acid at various concentrations as the crosslinker. The pullulan hydrogel patches prepared by the solvent casting method were studied the release behavior by using a modified franz diffusion cell with containing pH 5.5 and 7.4 buffer solution at 37 ◦C for 2 h. The amount of drug release was compared with various electrical potentials as 0, 0.5, 1, 3, and 5 V. The aspirin release behavior from pullulan hydrogel was a Non-Fickian mechanism meaning that the aspirin was released via concentration gradient combined with swelling behavior of drug matrix. The amount of drug release and releasing rate was decreased with increasing the crosslinking ratio because of the lower the swelling behavior of matrix. In addition, the applied electrical stimulation enhanced the amount of drug release and releasing rate. The maximum release of aspirin is approximately 25% within 9 min from the hydrogel patch using sodium trimetaphosphate as a crosslinker and a 5 V which is higher than that of 0 V as 16% within 12 min. [ABSTRACT FROM AUTHOR]

The present study proposes an innovative transdermal drug delivery system using ferrocene-incorporated fibers to enhance the bioavailability and therapeutic efficacy of ascorbyl tetraisopalmitate. Using electrospinning technology, the authors created ferrocene polymer fibers capable of highly efficient drug encapsulation and controlled release in response to reactive oxygen species commonly found in wound sites. The approach improves upon previous methods significantly by offering higher drug loading capacities and sustained release, directly targeting diseased cells. The results confirm the potential of ferrocene fibers for localized drug delivery, potentially reducing side effects and increasing patient convenience. The method could facilitate the application of bioactive compounds in medical textiles and targeted therapy. [ABSTRACT FROM AUTHOR]

A pioneering approach in the domain of transdermal drug delivery systems (TDDS) is introduced by using microneedles (MNs) fabricated from an amorphous solid dispersion comprising only a model drug and an amphiphilic block copolymer to form a drug nanoformulation upon MN dissolution. To maximize drug loading and ensure consistent release, a minimalist formulation that achieves 40 wt% drug loading, which is a significant improvement over existing methods, is developed. Using scanning electron microscopy, the morphology of MNs is examined across a spectrum of drug loading ratios, demonstrating the consistency in structure and integrity. Mechanical testing confirms the MNs' proficiency in effective skin penetration. A comparative study on the formation of polymeric micelles underscores the innovative concept of a “nano‐in‐micro drug delivery system”. The results demonstrate that MNs manufactured from an amorphous solid dispersion of drug and amphiphilic block copolymer with ultra‐high loading enhance the availability and release dynamics of hydrophobic drugs, positioning them as a tool for enhancing TDDS. This study sets a new benchmark in the utilization of polymer‐drug nanoformulations for transdermal applications and underscores the capacity for high drug loading and the creation of adaptable drug delivery mechanisms for the studied amphiphilic block copolymer. [ABSTRACT FROM AUTHOR]

Although metal‐organic framework (MOF)‐derived nanoporous C (NPC) materials offer several advantages for electrochemical sensor applications, surface functionalization and porosity tuning can affect sensor performance. This study presents the development of a skin patch for perspiration and electrocardiogram (ECG) monitoring, leveraging the unique properties of MOF‐on‐MOF‐derived surface‐functionalized hybrid nanoporous C (f‐HNPC) incorporated into laser‐scribed graphene (LSG). Hydroxyl (OH) group‐functionalized NPC, achieved through KOH activation, facilitates electron transport at the electrode–electrolyte interface. This enhances the electrochemical activity, thereby improving sensor sensitivity and expanding the detection range. The integration of f‐HNPC provides enhanced surface area and electrochemical properties, enabling sensitive and selective detection of sweat biomarkers, including glucose (103 µA mM−1 cm−2) and uric acid (184 µA mM−1 cm−2) along with an ultra‐wide glucose detection range (up to 41.5 mM). Moreover, the incorporation of LSG ensures excellent mechanical flexibility, facilitating conformal contact with the skin for reliable signal acquisition. The proposed skin patch demonstrates promising performance in real‐time perspiration analysis and ECG monitoring with a signal‐to‐noise ratio of 23.63 dB, along with high stability and long‐term durability. The synergistic combination of f‐HNPC and LSG shows great potential for developing advanced wearable biosensing platforms for personalized healthcare applications. [ABSTRACT FROM AUTHOR]

Background: Fentanyl is a highly potent analgesic, used in surgery, frequently abused or used in drug-facilitated crimes (DFC) and in military activities. It is also increasingly used in the treatment of chronic pain (especially in cancer patients). The improper use of transdermal patch forms can cause toxicity and deaths, related to overdose or combined use with other drug substances. Methods are needed for fast, reliable and inexpensive fentanyl detection and we aimed to develop such a method in urine using LC–MS/MS, especially for toxic and fatal concentrations which lack in the literature. Results: An LC–MS/MS method has been presented for the co-determination of fentanyl and its main metabolite, norfentanyl in urine. The recoveries of the extraction method were 95(± 6)% and 70(± 9)% for fentanyl and norfentanyl, respectively. LOD and LOQ values are 1.7 and 14.0 ng/mL for fentanyl, while they were 20.6 ng/mL and 42.0 ng/mL for norfentanyl. Conclusion: A rapid, sensitive, very practical, inexpensive and a high-recovery analysis method is developed and validated. This is the only fentanyl monitoring LC–MS/MS method in urine having a linearity over a wide range up to 500.0 ng/mL and its success is demonstrated on real samples in the therapeutic drug monitoring of fentanyl and is expected to contribute to clarify intoxications/deaths related to its use. [ABSTRACT FROM AUTHOR]

Bioinspired skin adhesives are promising alternatives to traditional glue‐based skin patches for use in various skin‐attachable devices. However, the typical nano‐/microfabrication of these bioinspired microstructures provides limited manufacturing freedom over their performance, constraining their versatility and customization for widespread use. In this study, a hybrid 3D printing approach for fabricating a permeable skin patch is developed with adhesive miniaturized octopus‐like suckers (AMOS) for biosignal monitoring. The design and geometrical influences are investigated on the adhesion strength under different skin conditions (i.e., dry, wet, and hairy), permeability, and durability as well as proposed a biocompatible, stretchable, highly permeable, reusable, and conformable biopatch. Unlike commercially available biopatches that use chemical adhesives, the adhesion strength of an AMOS patch is customizable, does not cause skin irritation, and is comfortable for the wearer when worn for extended durations. The biopatch is tested in electromyogram, electrooculogram, and electrocardiogram signal measurement during a hand‐cycling experiment over extended durations that confirms its potential in extreme sport events. In addition to biosignal monitoring, 3D‐printed AMOS patches have broad applicability across various skin‐interfacing devices, including glucose and sweat monitoring, drug delivery, and wound healing. This approach offers a promising and highly customizable manufacturing solution for unlocking next‐generation skin‐attachable technologies. [ABSTRACT FROM AUTHOR]

The transdermal route is considered one of the most favourable routes of drug delivery over other conventional routes. The stratum corneum (SC) is the main barrier to the delivery of drugs by the transdermal route. Many strategies are employed to overcome SC barrier properties like lipid vesicles, permeation enhancers, physical methods, etc. The main objective of this research article was to explore and compare a few chemical penetration enhancers in combination with physical means like tape stripping and microneedle to enhance the transdermal permeation of caffeine. The transdermal gel of caffeine was prepared by dissolving the drug in distilled water containing various concentrations of chemical penetration enhancers, including Arlasolve DMI, ethanol, transcutol P and DMSO. Ex-vivo skin permeation and skin deposition studies were conducted on the transdermal gel alone and in combination with the microneedle or tape-stripping methods. The HPLC method analyzed the total amount of caffeine that permeated through the skin sample. The formulations containing Arlasolve DMI as a penetration enhancer showed the maximum drug penetration among all the penetration enhancers. A combination of microneedles with Arlasolve DMI showed the best skin permeation among all the methods tested. It was clear from the results that Arlasolve DMI would be a better option to use as a penetration enhancer in the dermatological formulations of caffeine in combination with a microneedle-based permeation enhancement method. [ABSTRACT FROM AUTHOR]

The transdermal drug delivery system (TDDS) was created with the main goals of achieving extended pharmaceutical release, increasing bioavailability, and enhancing patient adherence. The matrix dispersion transdermal patch works by dispersing the drug and polymers in a solvent, which is then evaporated to leave a homogenous drug-polymer matrix. The goals of the present study were on designing and formulating TDDS for tirzepatide and afterwards assessing their in vitro performance characteristics. In diabetes mellitus, the pancreas either produces inadequate amounts of insulin or the body is unable to properly use the insulin that is generated. More than 415 million people worldwide have diabetes, and it is anticipated that by 2040, that number would reach 642 million. By 2030, diabetes will surpass heart disease as the seventh largest cause of death, according to the WHO. [ABSTRACT FROM AUTHOR]

This study focuses on the design, characterization, and optimization of nanostructured lipid carriers (NLCs) loaded with docetaxel for the treatment of skin cancer. Employing a systematic formulation development process guided by Design of Experiments (DoE) principles, key parameters such as particle size, polydispersity index (PDI), zeta potential, and entrapment efficiency were optimized to ensure the stability and drug-loading efficacy of the NLCs. Combined XRD and cryo-TEM analysis were employed for NLC nanostructure evaluation, confirming the formation of well-defined nanostructures. In vitro kinetics studies demonstrated controlled and sustained docetaxel release over 48 h, emphasizing the potential for prolonged therapeutic effects. Cytotoxicity assays on human umbilical vein endothelial cells (HUVEC) and SK-MEL-24 melanoma cell line revealed enhanced efficacy against cancer cells, with significant selective cytotoxicity and minimal impact on normal cells. This multidimensional approach, encompassing formulation optimization and comprehensive characterization, positions the docetaxel-loaded NLCs as promising candidates for advanced skin cancer therapy. The findings underscore the potential translational impact of these nanocarriers, paving the way for future preclinical investigations and clinical applications in skin cancer treatment. [ABSTRACT FROM AUTHOR]

A transdermal drug delivery system (TDDS) is characterized by the application of medications onto the skin's surface to deliver drugs at a controlled and predefined rate through the skin. Spanlastics, an elastic nanovesicle capable of transporting various pharmacological substances, shows promise as a drug delivery carrier. It offers numerous advantages over traditional vesicular systems applied topically, including enhanced stability, flexibility in penetration, and improved targeting capabilities. This study aims to develop meloxicam (MX)-loaded spanlastics gel as skin delivery carriers and to look into the effects of formulation factors like Tween80, Brij 35, and carbopol concentration on the properties of spanlastics gel, like pH, drug content, extrudability, spreadability diameter, viscosity, and release profiles in addition to Ex vivo skin permeation for optimal formula. The optimal formula of spanlastics gel (GF1) shows acceptable pH (6.2±0.14), excellent extrudability( 92%), drug content (97.1±0.14), spreadability diameter (cm) (10.8±0.28), sustained release 70.7±0.57% for six hours and the steady-state flux of meloxicam through rat skin was increased 83.52- fold as a result of spanlastics in comparison to the plain gel. The vesicles produced in this investigation could potentially interact with or merge with the stratum corneum as a result of their elasticity, which may also be the mechanism that increases the penetration into the skin. According to our findings, dermal delivery vehicles for MX may be provided via spanlastics gel. [ABSTRACT FROM AUTHOR]

Gene delivery has revolutionized conventional medical approaches to vaccination, cancer, and autoimmune diseases. However, current gene delivery methods are limited to either intravenous administration or direct local injections, failing to achieve well biosafety, tissue targeting, drug retention, and transfection efficiency for desired therapeutic outcomes. Transdermal drug delivery based on various delivery strategies can offer improved therapeutic potential and superior patient experiences. Recently, there has been increased foundational and clinical research focusing on the role of the transdermal route in gene delivery and exploring its impact on the efficiency of gene delivery. This review introduces the recent advances in transdermal gene delivery approaches facilitated by drug formulations and medical devices, as well as discusses their prospects. [Display omitted] [ABSTRACT FROM AUTHOR]

Photodamage is one of the most common causes of skin injury. High molecular weight hyaluronic acid (HHA) has shown immense potential in the treatment of skin photodamage by virtue of its anti-inflammatory, reparative, and antioxidative properties. However, due to its large molecular structure of HHA, HHA solution could only form a protective film on the skin surface in conventional application, failing to effectively penetrate the skin, which necessitates the development of new delivery strategies. Liposomes, with a structure similar to biological membranes, have garnered extensive attention as transdermal drug delivery carriers because of their advantages in permeability, dermal compatibility, and biosafety. Herein, we have developed a HHA-liposome transdermal system (HHL) by embedding HHA into the liposome structure using reverse evaporation, high-speed homogenization, and micro-jet techniques. The effective penetration and long-term residence of HHA in skin tissue were multidimensionally verified, and the kinetics of HHA in the skin were extensively studied. Moreover, it was demonstrated that HHL significantly strengthened the activity of human keratinocytes and effectively inhibits photo-induced cellular aging in vitro. Furthermore, a murine model of acute skin injury induced by laser ablation was established, where the transdermal system showed significant anti-inflammatory and immunosuppressive properties, promoting skin proliferation and scar repair, thereby demonstrating immense potential in accelerating skin wound healing. Meanwhile, HHL significantly ameliorated skin barrier dysfunction caused by simulated sunlight exposure, inhibited skin erythema, inflammatory responses, and oxidative stress, and promoted collagen expression in a chronic photodamage skin model. Therefore, this transdermal delivery system with biocompatibility represents a promising new strategy for the non-invasive application of HHA in skin photodamage, revealing the significant potential for clinical translation and broad application prospects. The transdermal system utilizing hyaluronic acid-based liposomes enhances skin permeability and retains high molecular weight hyaluronic acid (HHL). In vitro experiments with human keratinocytes demonstrate significant skin repair effects of HHL and its effective inhibition of cellular aging. In an acute photodamage model, HHL exhibits stronger anti-inflammatory and immunosuppressive properties, promoting skin proliferation and scar repair. In a chronic photodamage model, HHL significantly improves skin barrier dysfunction, reduces oxidative stress induced by simulated sunlight, and enhances collagen expression. [Display omitted] [ABSTRACT FROM AUTHOR]

Atorvastatin calcium is an antihyperlipidemic agent with low bioavailability due to the first-pass metabolism after oral administration. To overcome the limitation, an alternative method for delivering drug molecules to the systemic circulation is needed, such as transethosomes produced for transdermal delivery. Therefore, this study aimed to produce atorvastatin calcium transethosomes with characteristics suitable for transdermal delivery using validated analytical method. Transethosomes formulations were prepared with different concentrations of soy lecithin and ethanol. All formulations were evaluated for particle size, zeta potential, polydispersity index (PDI), drug content, and deformability index. Validation of the analytical method of atorvastatin calcium was carried out using system suitability, selectivity, linearity, limit of detection (LOD), limit of quantification (LOQ), precision, accuracy, and robustness. The result showed that transethosomes had a small particle size of 123.90 nm-165.10 nm, high zeta potential values, acceptable PDI, the highest atorvastatin calcium content, and good deformability index. In addition, the system suitability test results were acceptable and there was no interference in the atorvastatin calcium area. Linearity showed r =0.9999 with LOD and LOQ values of 0.388 µg/mL and 1.176 µg/mL, respectively. The % RSD in the precision was < 2 and the recovery in the accuracy was 98.76%-101.04%. The method proved to be robust with respect to mobile phase pH changes. Based on the results, atorvastatin calcium-loaded transethosomes were suitable for transdermal delivery and could be effectively produced with a 3% soy lecithin and 30% ethanol concentration. The analytical method for determining drug content of atorvastatin calcium-loaded transethosomes could be effectively applied. [ABSTRACT FROM AUTHOR]

The Sanskrit term Shweta, which meaning "white patch," is the root of the name Shwitra. Shwitra (Vitiligo) is a condition that is referenced in the classic Kushta Roga Chikitsa and affects a significant section of the pediatric population as a result of poor dietary and lifestyle choices. Shwitra "Shweta Bhava Michanti Shwitram" is what the Kashyapa Samhita says. Kilasa, Daruna, Aruna, and Shweta Kushta are some more names for it. In contemporary medicine, vitiligo is referred to as an auto immune illness and manifests as a white patch on the skin. A widespread, progressive, chronic skin illness called vitiligo is characterized by patches of skin with sharp, frequently hyperpigmented edges caused by a lack of melanin pigments. Approximately 1% of people worldwide suffer from this illness. This condition is included under the general topic of Shwitra in Ayurveda. Every Acharya has the same opinion that the two primary therapeutic modalities mentioned in the classics—Samshodhan Karma and Samshaman Karma— should be used to treat Shwitra or Kushtha first. In their various Samhitas, Acharyas have specified a variety of internal and external uses, as well as sun exposure, for Shaman Chikitsa in the Shwitra Roga. Samhitas discuss a wide range of single and combination medications; among them, Shwitrahar Kashaya and lepa are mentioned in detail. One of them is chosen and shown to be useful for the investigation. [ABSTRACT FROM AUTHOR]

Purpose: High-intensity focused ultrasound (HIFU)-assisted drug delivery is a non-invasive tool to deliver drugs to targeted areas, currently used mainly for treating cancer and cardiovascular diseases. However, in terms of transdermal drug delivery, HIFU technology is still poorly understood. Accordingly, this study sought to investigate the effectiveness of HIFU on drug penetration into the skin using human skin tissues. Methods: Gel-type drugs whose ingredient is glutathione were labelled with fluorescein isothiocyanate, in turn the drugs were allowed to penetrate to the human skin tissue in the Franz diffusion cell for 24 hours in control and HIFU treatment groups, and their fluorescence intensity was measured using a multiple microplate reader at one, two, six, and 24 hours after drug application. In addition, tissue slice analysis was performed in each tissue slice at 24 hours post-drug application. The % area, fluorescence intensity per area, and penetration depth of the drug were measured using a fluorescence microscope. Results: The fluorescence intensity increased with time in all groups. Specifically, at 24 hours after drug application, the fluorescence intensity (a.u). of the 10-shot HIFU treatment group was significantly enhanced compared to that of the control group (p < 0.05). The tissue slice analysis demonstrated that the % area of fluorescent drug and the fluorescence intensity per area (a.u.) were all significantly increased in both HIFU treatment groups compared to the control group (p < 0.05, p < 0.001). In addition, the penetration depth (μm) also markedly rose in both HIFU treatment groups compared to the control group (p < 0.01, p < 0.05). Conclusion: It was demonstrated for the first time that HIFU significantly facilitated topical drug penetration into the human skin, strongly implying that HIFU can be a useful option for transdermal drug delivery. [ABSTRACT FROM AUTHOR]

AbstractMicroneedles, as a new efficient and safe transdermal drug delivery technology, has a wide range of applications in drug delivery, vaccination, medical cosmetology, and diagnostics. The degree of microneedles penetration into the skin determines the reliability of the delivery dose, but its evaluation is not yet well-established, which is one of the major constraints in the commercialization of microneedles. In this paper, a novel visual simulated skin model was developed with reference to the physical properties of real skin. The simulated skin model was well-designed and its prescription was optimized to make the thickness, hardness, elasticity, and other parameters close to those of real skin. It not only meets the need to assess the degree of insertion of microneedles but also provides a visual observation of the insertion state of microneedles. [ABSTRACT FROM AUTHOR]

This article provides a comprehensive analysis of the impact of detergent chemistry on exceeding planetary boundaries, specifically focusing on antimicrobial resistance, drug development, and the integrity of the biosphere. The authors emphasize the need for a holistic approach to the chemical design of detergents and identify progress and knowledge gaps related to detergent chemistry and five planetary boundaries that are currently being exceeded. The study highlights three critical challenges that need to be addressed, including the development of a climate-friendly detergent industry, aligning materialistic and social aspects in sustainable chemistry, and creating detergents that serve a purpose without harming the biosphere. The article also discusses the potential of sustainable chemistry in promoting adherence to planetary boundaries and highlights the impact of detergent chemistry on human health and the environment. It concludes by suggesting that further research is needed to understand the effects of detergent molecules and to develop detergents that minimize their impact on the biosphere. [Extracted from the article]

Microneedles offer minimally invasive, user-friendly, and subcutaneously accessible transdermal drug delivery and have been widely investigated as an effective transdermal delivery system. Ibuprofen is a common anti-inflammatory drug to treat chronic inflammation. It is crucial to develop microneedle patches capable of efficiently delivering ibuprofen through the skin for the effective treatment of arthritis patients requiring repeated medication. In this study, the mechanical properties of a new type of polymer microneedle were studied by finite element analysis, and the experimental results showed that the microneedle could effectively deliver drugs through the skin. In addition, a high ibuprofen-loaded microneedle patch was successfully prepared by micromolding and subjected to evaluation of its infrared spectrum morphology and dissolve degree. The morphology of microneedles was characterized by scanning electron microscopy, and the mechanical properties were assessed using a built linear stretching system. In the in-vitro diffusion cell drug release test, the microneedle released 85.2 ± 1.52% (210 ± 3.7 μg) ibuprofen in the modified Franz diffusion within 4 h, exhibiting a higher drug release compared to other drug delivery methods. This study provides a portable, safe and efficient treatment approach for arthritis patients requiring daily repeated medication. [ABSTRACT FROM AUTHOR]

The aim of this study was to develop and evaluate the transdermal patch formulations of nifedipine. The patch formulations containing nifedipine were prepared and optimized with different ratios of vinyl and cellulose-derived polymers, drug contents, and permeation enhancers. Among the various formulations, the patch formulation containing a 1:5 ratio of ethyl cellulose and polyvinyl pyrrolidone was selected for ex vivo pharmacokinetic study based on in vitro permeation studies using stratum corneum of the pig's skin. The cumulative percentage release after the transdermal administration of the optimized patch formulation was 71.43%, and the plasma concentration of nifedipine was maintained for 16 hrs. The physicochemical evaluation study including flatness, thickness, moisture content and uptake, drug content in vitro release, and ex vivo permeation indicated satisfactory results. The formulation batch with clove oil as a penetration enhancer has shown better ex vivo permeation as compared to the formulations without enhancers and another synthetic enhancer. These results suggest that the optimized patch formulation Q3 could be further developed for clinical applications, providing the therapeutic plasma level of nifedipine over an extended period. Hence analyzing the results of the evaluation tests, in vitro and ex vivo data on the preparation and optimization of nifedipine-loaded transdermal patch, it can be concluded that the formulation shows its feasibility as an effective transdermal delivery system for nifedipine. [ABSTRACT FROM AUTHOR]

Organ-on-a-chip technologies show exponential growth driven by the need to reduce the number of experimental animals and develop physiologically relevant human models for testing drugs. In vitro, microfluidic devices should be carefully designed and fabricated to provide reliable tools for modeling physiological or pathological conditions and assessing, for example, drug delivery through biological barriers. The aim of the current study was to optimize the utilization of three existing skin-on-a-chip microfluidic diffusion chambers with various designs. For this, different perfusion flow rates were compared using cellulose acetate membrane, polyester membrane, excised rat skin, and acellular alginate scaffold in the chips. These diffusion platforms were integrated into a single-channel microfluidic diffusion chamber, a multi-channel chamber, and the LiveBox2 system. The experimental results revealed that the 40 µL/min flow rate resulted in the highest diffusion of the hydrophilic model formulation (2% caffeine cream) in each system. The single-channel setup was used for further analysis by computational fluid dynamics simulation. The visualization of shear stress and fluid velocity within the microchannel and the presentation of caffeine progression with the perfusion fluid were consistent with the measured data. These findings contribute to the development and effective application of microfluidic systems for penetration testing. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate Zn/Ag-electrode-printed patches for the transdermal delivery of small molecules through iontophoresis. The Zn/Ag-electrode-printed patches interact with biological liquid electrolytes and generate suitable microcurrents for the iontophoretic delivery of small molecules across the skin. In fluorescein permeation studies, Zn/Ag-electrode-printed patches increased the transdermal depth of fluorescein into the dermis, while the permeation of fluorescein was limited when Zn/C-electrode-printed patches were tested. Further permeation experiments were conducted with 3D skin models, which showed a similar trend to the above, indicating that Zn/Ag-electrode-printed patches had a higher penetration rate compared to the blank. Studies using acetyl hexapeptide-8 as a peptide drug model and sodium ascorbyl phosphate (SAP) as a hydrophilic derivative of ascorbic acid showed that the iontophoretic patch with Zn/Ag electrodes promoted more penetration of drugs than unprinted patches. The permeation of SAP exhibited a two-phase profile with a relatively rapid permeation followed by a sustained, slower permeation. The permeation of acetyl hexapeptide-8 was slower due to its higher molecular weight, but the iontophoretic patch increased the permeation up to 1.5 times more than the unprinted patch. The microcurrent generated by the patch drives the transport of small molecule components through the skin, for the controlled and efficient delivery of therapeutic agents. The flexible design, efficient microcurrent generation, and stable electrodes make the Zn/Ag-electrode-printed patch a promising tool for transdermal drug delivery. [ABSTRACT FROM AUTHOR]

Background: Capsaicin is a highly selective agonist of the transient receptor potential vanilloid 1. The adhesive capsaicin patch provides a high capsaicin concentration (8%) directly in the painful area – its efficacy in benign peripheral neuropathic pain (diabetic neuropathy or postherpetic neuralgia) has recently been described in the literature. However, there is scant evidence of its efficacy in chemotherapy-induced peripheral neuropathy (CIPN). This is a concern for patients with multiple myeloma, who suffer from peripheral neuropathic pain induced by first-line treatments (bortezomib or thalidomide). Aim: To describe improved control of CIPN in patients with multiple myeloma using adhesive capsaicin 8% patch. Methods: We opted for a retrospective observational case series. Between October 2017 and October 2020, we collected clinical data from adult multiple myeloma patients affected by CIPN who were administered the capsaicin 8% patch in our palliative care outpatient clinic. We compiled Numerical Pain Rating Scale (NPRS) scores, patients' medication needs and performance status before and after patch application. Results: Two women and five men with an average age of 62.85 years received bortezomib. Two patients (28.57% of the sample) also received thalidomide. The average NPRS score before patch application was 6.42/10. Five of the seven patients (71.42%) received a mean daily oral morphine dose of 52.85 mg/day, five (71.42%) received gabapentinoids and one (14.28%) received antidepressants. The average NPRS score decreased to 4/10 seven days after patch application, while the mean daily oral morphine dose remained stable. Performance status improved slightly in two patients (28.57%) and remained stable in the rest. One patient (14.28%) required an extra analgesic dose during patch application. Conclusions: Capsaicin 8% patch application appears to reduce pain intensity in patients with multiple myeloma suffering from CIPN. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the efficacy and safety of transdermal glycerol trinitrate skin patches as an additive and effective agent for facilitating cervical ripening for labour induction. Methods: This was a double-blinded prospective randomised clinical trial carried out in a major obstetric unit in India. Women who planned for labour induction were randomly allocated for induction either by combined application of glycerol trinitrate skin patches [GTN patch] and intracervical dinoprostone gel or by the gel only. Sample randomisation was done using a stratified block randomisation technique with a sealed envelope. The numbers designating the group allocation sequence were concealed from doctors, research staff, and investigators. Six hourly improvements were assessed in the modified Bishop's score, induction-delivery time interval, the need for oxytocin, maternal side effects and foetal outcomes. Data were analysed using SPSS software. Results and discussion: Recruitment Bishop scores, parity and gestational age were matched in both cases and the control group. The modified Bishop's score was statistically improved in study groups, as evidenced compositely and irrespective of parity. The two groups appeared to have no significant differences regarding other outcomes. The additional application of the GTN patch seems helpful to accelerate the progress of labour but could not yield any favourable labour outcome. The GTN patch does not impose additional feto-maternal adverse effects apart from increased incidences of headaches. [ABSTRACT FROM AUTHOR]

Background Palmoplantar psoriasis (PPP) is a localized variant of psoriasis that may be resistant to topical therapy, owing to the poor penetrability of topical agents at this anatomical site. Modalities that enhance localized cutaneous delivery of drugs could help to solve this problem. Iontophoresis is one such procedure that augments transdermal drug delivery, thus enabling better and expeditious therapeutic outcomes. Objective To compare the therapeutic efficacy and safety of iontophoresis with tretinoin 0.05% cream and tacrolimus 0.1% ointment in treating patients with PPP. Methods Sixty patients with PPP (28 males and 32 females, age range 8–76 years) were enrolled and randomly assigned to one of two groups comprising 30 patients each. One group (12 males and 18 females) received iontophoresis with tretinoin 0.05% cream; the other (16 males and 14 females) received iontophoresis treatment with tacrolimus 0.1% ointment. Both groups received treatment weekly from baseline until 4 weeks and then fortnightly at weeks 6 and 8. Clinical images were taken at each visit and improvement of psoriasis was evaluated using the erythema, scaling, induration and fissuring (ESIF) score. The percentage reduction in ESIF score was also assessed on completion of treatment and the grade of improvement noted for each patient. Results Twenty-seven patients in the iontophoresis with tretinoin 0.05% cream group and 29 in the iontophoresis treatment with tacrolimus 0.1% ointment group completed the study. The mean (SD) ESIF score in the former decreased significantly from 8.7 (2) at baseline to 3.2 (1.7) at the study endpoint (P < 0.001). Similarly, in the latter group, there was a substantial reduction in mean (SD) ESIF score from 8.2 (1.9) at baseline to 3.3 (1.1) at the study end (P < 0.001). No significant adverse effects were encountered in either treatment arm. Conclusions Iontophoresis using tretinoin and tacrolimus was found to be effective and safe for the treatment of PPP. Although iontophoresis with tretinoin showed slightly better results than with tacrolimus, these were not statistically significant. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases (NDs), particularly dementia, provide significant problems to worldwide healthcare systems. The development of therapeutic materials for various diseases has a severe challenge in the form of the blood–brain barrier (BBB). Transdermal treatment has recently garnered widespread favor as an alternative method of delivering active chemicals to the brain. This approach has several advantages, including low invasiveness, self-administration, avoidance of first-pass metabolism, preservation of steady plasma concentrations, regulated release, safety, efficacy, and better patient compliance. Topics include the transdermal method for therapeutic NDs, their classification, and the mechanisms that allow the medicine to enter the bloodstream through the skin. The paper also discusses the obstacles and potential outcomes of transdermal therapy, emphasizing the benefits and drawbacks of different approaches. [ABSTRACT FROM AUTHOR]

Transdermal drug delivery offers a promising alternative for administering medications like ibuprofen, known for its analgesic and anti-inflammatory properties, with reduced gastrointestinal side effects compared to oral administration. This study explored the potential synergistic effects of combining ibuprofen with lavender essential oil (LEO) in transdermal patches. The composition of LEO was analyzed, revealing predominant compounds such as linalyl acetate and linalool, which are known for their analgesic and anti-inflammatory properties. The physicochemical properties of the patches were investigated, indicating improved cohesion with the addition of LEO. Additionally, thermal stability assessments demonstrated enhanced stability with LEO incorporation with an increase in onset decomposition temperature from 49.0 to 67.9 °C. The antioxidant activity of patches containing LEO was significantly higher with a free radical scavenging ability of 79.13% RSA compared to 60% RSA in patches without LEO. Release and permeation studies showed that patches with LEO exhibited an increased permeation of ibuprofen through the skin with 74.40% of the drug released from LEO-containing patches compared to 36.29% from patches without LEO after 24 h. Moreover, the permeation rate was notably faster with LEO, indicating quicker therapeutic effects. The inclusion of LEO in transdermal patches containing ibuprofen holds promise for enhancing drug delivery efficiency and therapeutic effectiveness, offering a potential strategy for improved pain management with reduced side effects. [ABSTRACT FROM AUTHOR]

Most drugs have not been evaluated in the older population. Recognizing physiological alterations associated with changes in drug disposition and with the ultimate effect, especially in central nervous system-acting drugs, is fundamental. While considering pharmacokinetics, it should be noted that the absorption of most drugs from the gastrointestinal tract does not change in advanced age. There are only few data about the effect of age on the transdermal absorption of medications such as fentanyl. Absorption from an intramuscular injection may be similar in older adults as in younger patients. The distribution of lipophilic drugs (such as diazepam) is increased owing to a relative increase in the percentage of body fat, causing drug accumulation and prolonged drug elimination following cessation. Phase I drug biotransformation is variably decreased in aging, impacting elimination, and hepatic drug clearance has been shown to decrease in older individuals by 10–40% for most drugs studied. Lower doses of phenothiazines, butyrophenones, atypical antipsychotics, antidepressants (citalopram, mirtazapine, and tricyclic antidepressants), and benzodiazepines (such as diazepam) achieve the same extent of exposure. For renally cleared drugs with no prior metabolism (such as gabapentin), the glomerular filtration rate appropriately estimates drug clearance. Important pharmacodynamic changes in older adults include an increased sedative effect of benzodiazepines at a given drug exposure, and a higher sensitivity to mu opiate receptor agonists and to opioid adverse effects. Artificial intelligence, physiologically based pharmacokinetic modeling and simulation, and concentration-effect modeling enabling a differentiation between the pharmacokinetic and the pharmacodynamic effects of aging might help to close some of the gaps in knowledge. [ABSTRACT FROM AUTHOR]

The transdermal route is an important delivery system for the delivery of both systemic and local effects. The effectiveness of therapy is based on adherence of transdermal dosage form to the skin and physiochemical properties of the drug during therapy. Transdermal Film-Forming Gels when applied to the skin after adherence form a thin film and provide the delivery of drug to the body tissues. Novel 5-Fluorouracil loaded Film-Forming Gels was prepared by utilizing natural polymer (chitosan) with variable concentration of penetration enhancers i.e. oleic acid and tween 80 which further affects the drug release. Prepared Film-Forming Gels were subjected to pH determination, viscosity measurement, homogeneity determination and FTIR analysis. Drying test showed film-forming gel was dried within 15 min after application. Moreover, in-vitro release study confirmed the 83% release over 180 min and the ex-vivo release of FFG9 displayed 81.45% release. This novel system would be an effective dosage form for the delivery of drugs. [ABSTRACT FROM AUTHOR]

Objective: The objective of the present study was to enhance the bioavailability of cannabidiol (CBD) using 3D Digital Light Processing (DLP)-printed microneedle (MN) transdermal drug delivery system. Methods: CBD MN patch was fabricated and optimized using 3D DLP printing using CBD (8% w/v), Lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) (0.49% w/v), distilled water (20% w/v), and poly (ethylene glycol) dimethacrylate 550 (PEGDAMA 550) (up to 100% w/v). CBD MNs were characterized for their morphology, mechanical strength, in vitro release study, ex vivo permeation study, and in vivo pharmacokinetic (PK) profile. Key findings: Microscopic images showed that sharp CBD MNs with a height of ~800 μm, base diameter of ~250 μm, and tip with a radius of curvature (RoC) of ~15 μm were successfully printed using optimized printing parameters. Mechanical strength studies showed no significant deformation in the morphology of CBD MNs even after applying 0.5N/needle force. Ex vivo permeation study showed significant (P <.0001) permeation of CBD in the receiving media as compared to CBD patch (control). In vivo PK study showed significantly (P <.05) enhanced bioavailability in the case of CBD MN patch as compared to CBD subcutaneous inj. (control). Conclusion: Overall, systemic absorption of CBD was significantly enhanced using 3D-printed MN drug delivery system. Graphical Abstract [ABSTRACT FROM AUTHOR]

Aim: Behavioral psychological symptoms of dementia (BPSD) are sometimes difficult to treat due to severe psychiatric symptoms such as delusions of poisoning and violent behavior. Moreover, in cases of parental neglect, the management of these psychiatric symptoms becomes more difficult. Therefore, home‐visiting doctors sometimes have to manage patients with BPSD and severe psychiatric symptoms, and a new approach is needed. In this case report, the effect of blonanserin transdermal patch on these patients is to be highlighted. Methods: The patient is a 91‐year‐old woman diagnosed with Alzheimer's disease. She had severe BPSD such as delusion of robbery and violent behavior, and refused oral medications including memantine and yokukansan. Then she was treated with blonanserin transdermal patch (20 mg/day). The severity of psychiatric symptoms of BPSD was assessed over time using the Neuropsychiatric Inventory (NPI) score. Moreover, the patient's cognitive function was also assessed over time by Mini‐Mental State Examination (MMSE). Results: After the introduction of blonanserin patch, the patient's psychiatric symptoms were stabilized markedly, and both NPI and MMSE scores improved. The patient was able to stay at home calmly and was mentally well stabilized to the extent that she did not require hospitalization. No apparent side effects were admitted. Conclusions: The blonanserin transdermal patch may be able to manage BPSD at home and is effective in patients who refuse oral medications. Home‐visiting doctors may consider the use of blonanserin patches at home for patients with severe BPSD, manifesting as delusions of poisoning and refusing oral drugs. [ABSTRACT FROM AUTHOR]

Alpha-2 agonists are under-recognized for their class effects yet offer potential benefit in specialty palliative care via decreasing sympathetic output, inducing sedation, and modulating pain. Especially in clinical contexts where agitation predominates and patients are intolerant of oral medication route, transdermal medication delivery is advantageous. We report a case of agitated behaviors in setting of mixed Alzheimer/vascular-type dementia limiting hospital discharge to nursing facility that were ameliorated with transdermal clonidine. We suggest palliative clinicians routinely conceptualize the seemingly disparate alpha-2 agonists as a class for effective symptom palliation especially as new clinical evidence becomes available. [ABSTRACT FROM AUTHOR]

Subcutaneous patient-controlled analgesia (SCPCA) in home-based palliative care is a potentially valuable option for providing effective pain relief to some patients, particularly when conventional analgesic approaches prove ineffective or are refused. Our case report illustrates the use of SPCA for the management of breakthrough pain in a patient receiving palliative care at home with no improvement after multiple previous treatments. SCPCA was found to be safe and successful. Future research is essential to explore its precise role, appropriate indications, prescription guidelines, and safety considerations across various palliative care contexts. [ABSTRACT FROM AUTHOR]

Background: The transdermal patch of bisoprolol available in Japan has been reported to demonstrate superior efficacy in preventing postoperative atrial fibrillation, possibly surpassing its oral counterpart. However, there has been no systematic review and meta-analysis assessing the efficacy of transdermal bisoprolol. Methods: A comprehensive systematic literature search was conducted on PubMed, Embase, and Cochrane to identify all relevant studies assessing the efficacy of transdermal bisoprolol in preventing postoperative atrial fibrillation. The search covered studies from inception up to December 4, 2023. For data analysis, Review Manager (RevMan) 5.4 software was employed, using a random-effects model to calculate risk ratios (RR) and 95% confidence intervals (CI). Results: Three studies, comprising a total of 551 patients (transdermal bisoprolol 228 and control 323), were included. There was a decreased risk of postoperative atrial fibrillation or atrial tachyarrhythmias in patients treated with transdermal bisoprolol (RR 0.43, 95% CI 0.27--0.67, p = .0002, I² = 0%). Conclusion: Transdermal administration of bisoprolol has consistently shown efficacy, and this pooled analysis supports its effectiveness. The heterogeneity of the included studies limits certain interpretations. Future randomized clinical trials may elucidate the superiority of transdermal administration over oral administration. [ABSTRACT FROM AUTHOR]

In transdermal drug delivery system (TDDS) patches, achieving prolonged adhesion, high drug loading, and rapid drug release simultaneously presented a significant challenge. In this study, a PHT-SP-Cu2+ adhesive was synthesized using polyethylene glycol (PEG), hexamethylene diisocyanate (HDI), trimethylolpropane (TMP), and silk protein (SP) as functional monomers which were combined with Cu2+ to improve the adhesion, drug loading, and drug release of the patch. The structure of the adhesion chains and the formation of Cu2+-p-π conjugated network in PHT-SP-Cu2+ were characterized and elucidated using different characterization methods including FT-IR, 13C NMR, XPS, SEM imaging and thermodynamic evaluation. The formulation of pressure-sensitive adhesive (PSA) was optimized through comprehensive research on adhesion, mechanics, rheology, and surface energy. The formulation of 3 wt.% SP and 3 wt.% Cu2+ provided superior adhesion properties compared to commercial standards. Subsequently, the peel strength of PHT-SP-Cu2+ was 7.6 times higher than that of the commercially available adhesive DURO-TAK® 87–4098 in the porcine skin peel test. The adhesion test on human skin confirmed that PHT-SP-Cu2+ could adhere to the human body for more than six days. Moreover, the drug loading, in vitro release test and skin permeation test were investigated using ketoprofen as a model drug, and the results showed that PHT-SP-Cu2+ had the efficacy of improving drug compatibility, promoting drug release and enhancing skin permeation as a TDDS. Among them, the drug loading of PHT-SP-Cu2+ was increased by 6.25-fold compared with PHT, and in the in vivo pharmacokinetic analysis, the AUC was similarly increased by 19.22-fold. The mechanism of α-helix facilitated drug release was demonstrated by Flori-Hawkins interaction parameters, molecular dynamics simulations and FT-IR. Biosafety evaluations highlighted the superior skin cytocompatibility and safety of PHT-SP-Cu2+ for transdermal applications. These results would contribute to the development of TDDS patch adhesives with outstanding adhesion, drug loading and release efficiency. A new adhesive, PHT-SP-Cu2+, was created for transdermal drug delivery patches. Polyethylene glycol, hexamethylene diisocyanate, trimethylolpropane, silk protein, and Cu2+ were used in synthesis. Characterization techniques confirmed the structure and Cu2+-p-π conjugated networks. Optimal formulation included 3 wt.% SP and 3 wt.% Cu2+, exhibiting superior adhesion. PHT-SP-Cu2+ showed 7.6 times higher peel strength than DURO-TAK® 87–4098 on porcine skin and adhered to human skin for over six days. It demonstrated a 6.25-fold increase in drug loading compared to PHT, with 19.22-fold higher AUC in vivo studies. α-helix facilitated drug release, proven by various analyses. PHT-SP-Cu2+ showed excellent cytocompatibility and safety for transdermal applications. This study contributes to developing efficient TDDS patches. [Display omitted] [ABSTRACT FROM AUTHOR]