Transdermal Drug Delivery Research Articles

Novel extended-release transdermal formulations of the psychedelic N,N-dimethyltryptamine (DMT)

There is considerable evidence from the literature that psychedelics, such as N,N-dimethyltryptamine (DMT), are safe and effective treatments for depression. However, clinical administration to induce psychedelic effects and expensive psychotherapy-assisted treatments likely limit accessibility to the average patient. There is emerging evidence that DMT promotes positive behavioral changes in vivo at sub-hallucinogenic dosages, and depending on the target indication, subjecting patients to high, bolus dosages may not be necessary. Due to rapid metabolic degradation, achieving target levels of DMT in subjects is difficult, requiring IV administration, which poses risks to patients during the intense hallucinogenic and subjective drug effects. The chemical and physical properties of DMT make it an excellent candidate for non-invasive, transdermal delivery platforms. This paper outlines the formulation development, in vitro, and in vivo testing of transdermal drug-in-adhesive DMT patches using various adhesives and permeation enhancers. In vivo behavioral and pharmacokinetic studies were performed with lead patch formulation (F5) in male and female Swiss Webster mice, and resulting DMT levels in plasma and brain samples were quantified using LC/MS/MS. Notable differences were seen in female versus male mice during IV administration; however, transdermal administration provided consistent, extended drug release at a non-hallucinogenic dose. The IV half-life of DMT was extended by 20-fold with administration of the transdermal delivery system at sub-hallucinogenic plasma concentrations not exceeding 60 ng/mL. Results of a translational head twitch assay (a surrogate for hallucinogenic effects in non-human organisms) were consistent with absence of hallucinations at low plasma levels achieved with our TDDS. Despite the reported low bioavailability of DMT, the non-invasive transdermal DMT patch F5 afforded an impressive 77 % bioavailability compared to IV at two dosages. This unique transdermal delivery option has the potential to provide an out-patient treatment option for ailments not requiring higher, bolus doses and is especially intriguing for therapeutic indications requiring non-hallucinogenic alternatives.

An Overview of Transferosomal Technology

Abstract: Ever since the invention of liposomes by Bangham in 1963, researchers have been fascinated by the vesicular carriers. Liposomes and niosomes have been used extensively by researchers for various routes such as oral and nasal. However, lately, it has been understood that traditional liposomes are not very significant when it comes to penetration. The use of nanovesicles in transdermal drug delivery systems has been enhanced exponentially ever since the discovery of ultra- deformable liposomes known as transfersomes or transferosomes. Transferosomes have numerous advantages, such as biocompatibility, biodegradability, flexibility, and deformability, so that they can pass through narrow constrictions. They have good entrapment efficiency and can act as a depot to sustain the release of drugs. The methods of preparation include the rotary film evaporation method, reverse phase evaporation method, vortexing sonication method, ethanol injection method, and freeze-thaw method. Transfersomes are characterized by particle size, zeta potential, polydispersity index, surface morphology, and encapsulation efficiency. Transferosomes have been successfully exploited for the enhancement of efficacy of many drugs like Hydroquinone, Itraconazole, Ivabradine, lornoxicam, minoxidil etc., via transdermal and nasal routes. The technology is easy to scale up. Consequently, it can be inferred that transfersomes are the future of transdermal drug delivery systems.

Local therapy in the postoperative management of patients with lower limb varicose vein disease

Introduction. Varicose veins of the lower extremities are one of the most common diseases, affecting 20 to 40% of the population. One of the most common treatment methods is endovenous laser coagulation (EVLC).Aim. To evaluate the effectiveness of local gel therapy based on escin, heparin and essential phospholipids in the postoperative administration of patients after endovenous laser coagulation.Materials and methods. A complex treatment of 53 patients with varicose veins of the lower extremities of classes C2-C3 according to the CEAP nomenclature was carried out. Patients were divided into 2 statically homogeneous groups with an equal number. All patients underwent endovenous laser obliteration of the trunk of the great saphenous vein in combination with miniphlebectomy of tributaries on the thigh and lower leg.Results. In both groups, the largest number were patients with incompetence of the GSV trunk up to the border in /3 and c/3 of the lower leg, with further discharge along the tributaries of the GSV along the medial surface of the lower leg. The failure of the GSV trunk to the level of the knee joint gap was accompanied by the presence of varicose-transformed tributaries along the anterior surface of the thigh, in the area of the knee joint. The addition of Detragel led to the relief of phlebitis and hematomas, a pronounced decrease in pain and edematous syndrome.Discussion. Transdermal drug delivery has great promise as an alternative to oral and intravenous treatment, especially for patients suffering from chronic diseases. The three-component composition allows you to influence all parts of the pathogenesis of the disease.Conclusion. The data obtained on the use of local gel therapy based on escin, heparin and essential phospholipids after EVLO of the GSV indicate the need for local therapy to improve the quality of life of patients, their rapid rehabilitation and improve immediate and long-term results.

Strategies to Improve the Transdermal Delivery of Poorly Water-Soluble Non-Steroidal Anti-Inflammatory Drugs.

The transdermal delivery of non-steroidal anti-inflammatory drugs (NSAIDs) has the potential to overcome some of the major disadvantages relating to oral NSAID usage, such as gastrointestinal adverse events and compliance. However, the poor solubility of many of the newer NSAIDs creates challenges in incorporating the drugs into formulations suitable for application to skin and may limit transdermal permeation, particularly if the goal is therapeutic systemic drug concentrations. This review is an overview of the various strategies used to increase the solubility of poorly soluble NSAIDs and enhance their permeation through skin, such as the modification of the vehicle, the modification of or bypassing the barrier function of the skin, and using advanced nano-sized formulations. Furthermore, the simple yet highly versatile microemulsion system has been found to be a cost-effective and highly successful technology to deliver poorly water-soluble NSAIDs.

Nano-Formulation Approaches to Enhance Transdermal Drug Delivery-An Updated Review of Nanovesicular Carrier "Transethosomes".

Transdermal drug delivery is an attractive and patient-friendly route for administering therapeutic agents. However, the skin's natural barrier, the stratum corneum, restricts the passage of many drugs, limiting their effectiveness. To overcome this challenge, researchers have developed various nanocarriers to enhance drug penetration through the skin. Transethosomes, a novel and promising drug delivery system, have emerged as an innovative solution for improving transdermal drug delivery. Transethosomes are a hybrid of two established nanocarriers: ethosomes and transfersomes. Ethosomes are lipid-based vesicles that can accommodate lipophilic and hydrophilic drugs, while transfersomes are deformable lipid vesicles designed to enhance skin penetration. Transethosomes combine the advantages of both systems, making them ideal candidates for efficient transdermal drug delivery. They are composed of phospholipids, ethanol, and water and exhibit high flexibility, enabling them to squeeze through the tight junctions of the stratum corneum. This abstract reviews the key characteristics of transethosomes, including their composition, preparation methods, mechanisms of action, characterization parameters, and prospects. Moreover, the recent advancements and applications of transethosomes in delivering various therapeutic agents, such as analgesics, anti-inflammatories, hormones, and skincare products, are explored. The enhanced skin penetration capabilities of transethosomes can potentially reduce systemic side effects and improve patient compliance, making them a valuable tool in the field of transdermal drug delivery. In conclusion, transethosomes represent a promising platform for overcoming the challenges of transdermal drug delivery. Their unique properties enable efficient drug permeation through the skin, offering a more controlled and effective means of administering a wide range of pharmaceutical and cosmetic products. This abstract highlights the potential of transethosomes as a valuable addition to the field of transdermal drug delivery and paves the way for further research and development in this area.

Formulation and Evaluation of Betulin Loaded Transdermal Patches

Objectives: To develop and evaluate Transdermal patches of Betulin along with various polymers for controlled release action. Method: Suitable method such as Solvent Casting Technique of Film Casting Technique are used for preparation of Transdermal patch. Result: The prepared Transdermal patches were transparent, smooth, uniform and flexible. The method adopted for preparation of system was found satisfactory. Conclusion: Various formulations were developed by using hydrophilic and hydrophobic polymers like HPMC E5 and EC respectively in single and combinations by solvent evaporation technique with incorporation of penetration enhancer such as dimethylsulfoxide and dibutyl phthalate as plasticizer. Formulation F7 containing equal ratio of HPMC E5: EC (5:5) showed maximum percentage drug content 95.44%. A suitable UV Spectroscopy method for the analysis of Betulin was developed. Betulin showed maximum absorption at wave length 215 nm in isotonic phosphate buffer (pH 7.4) solutions. The pre-formulation studies involving description, solubility, melting point, partition coefficient of the drug were found to be comparable with the standard. The Transdermal patch of Betulin was prepared successfully by solvent evaporation method. Transdermal patch of Betulin for Transdermal drug delivery was evaluated. Calibration curve was obtained; Transdermal film was prepared, overcome limitations regarding bioavailability of drug was done. Keywords: Controlled DDS, Transdermal DDS, Betulin, Transdermal Patch, solvent evaporation method.

A small review on recent advances in transdermal drug delivery system

Transdermal drug delivery devices (TDDS), often known as "patches," are dosage forms designed to transfer a therapeutically effective amount of medicine over a patient's skin. Transdermal distribution establishes one of the most important channels for a revolutionary medication delivery method. Transdermal drug delivery has various advantages over traditional delivery methods, such as oral and injection; however, its efficacy is restricted. Transdermal administration traditionally entails pushing a patch containing a medicinal substance onto the skin, which is both convenient and painless, as well as therapeutic first-pass metabolism. It can deliver medications through the skin portal to systemic circulation at a predefined rate while maintaining therapeutically efficacious concentrations for an extended period of time. Around 74% of medications are taken orally, and one has been discovered to be less effective than expected.In this present review article, it covers a brief outline of various recent approaches in their development for transdermal patches.

ASSESSING THE SAFETY PROFILE OF POLYMERS IN TRANSDERMAL MICRONEEDLE PATCH FABRICATION: INSIGHTS FROM AN ACUTE TOXICITY STUDY

The acute toxicity study is a crucial component of preclinical toxicology assessments conducted to evaluate the potential adverse effects of a substance or compound on albino rabbits. This study provides key findings and implications of an acute toxicity study of natural and synthetic polymers that are used in the preparation of transdermal microneedle patches (TMNPs) for sustained delivery of doxazocin mesylate. In this study, we divided the albino rabbits into three equal groups (n = 6). Group-I was labeled as a control group and group-II was treated with TMNPs-1 (HPMC, maltose) and group-III was treated with TMNPs-2 (PLGA, polyvinyl acetate). The results obtained from feed consumption, hematology profile, biochemical studies, vital organ weight, and histopathological changes in vital organs were compared with the control group, and proved the safety profile of the polymers involved in the fabrication of microneedle patches. Mechanical strength and dermal safety study established the facts about the safety of microneedle patches and potential risks to health as a carrier system for the delivery of drugs into the systemic circulation directly.

Numerical modeling of ultrasound-triggered microneedle-mediated delivery of drug particles into bacterial biofilms

Ultrasonic microneedle patches, a class of ultrasound-driven transdermal drug delivery systems, are promising in addressing bacterial biofilms. This device has been proven to be more effective in treating Staphylococcus aureus biofilms than drug in free solution. However, there exists a notable gap in understanding how various excitation conditions and material parameters affect drug delivery efficiency. This study aims to fill this void by conducting an comprehensive multi-physics numerical analysis of ultrasonic microneedle patches, with the ultimate goal of enhancing drug delivery. First, we investigate the impact of various ultrasound frequencies on drug penetration depths. The findings reveal that local resonance can accelerate drug release within a shorter time window (first 1.5 h), whereas non-resonant frequencies enable more profound and prolonged diffusion. This information is crucial for medical professionals in selecting the most effective frequency for optimal drug administration. Furthermore, our investigation extends to the effects of applied voltage on temperature distribution, a critical aspect for ensuring medical safety during the application of these patches. Additionally, we examine how particles of different sizes respond to acoustic pressure and streaming fields, providing valuable insights for tailoring drug delivery strategies to specific therapeutic needs. Overall, our findings offer comprehensive guidelines for the effective use of ultrasonic microneedle patches, potentially shifting the paradigm in patient care and enhancing the overall quality of life.

High molecular weight hyaluronic acid-liposome delivery system for efficient transdermal treatment of acute and chronic skin photodamage

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. Statement of significanceThe 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.

Development and optimization of Lamotrigene containing Liposomal Transdermal Patches

Development and optimization of Lamotrigene containing Liposomal Transdermal Patches

Advancing Transdermal Delivery by Zn/Ag-Electrode-Printed Iontophoretic Patch with Self-Generating Microcurrents

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.

Pluronic P123/DMSO Lyotropic Liquid Crystal for Incorporating Bioactive Substances for Topical Application.

Lyotropic liquid crystals (LLCs) have attracted considerably growing interest in drug delivery applications over the last years. The structure of LLC matrices is complementary to cell membranes and provides an efficient, controlled, and selective release of drugs. In this work, a complex of experimental methods was used to characterize binary LLCs Pluronic P123/DMSO and triple LLC systems Pluronic P123/DMSO/Ibuprofen, which are interesting as transdermal drug delivery systems. Liquid crystalline, thermal, and rheological properties of LLCs were studied. Concentration and temperature areas of the lyomesophase existence were found, and phase transition enthalpies were evaluated. Intermolecular interactions among the components were studied by infrared (IR) spectroscopy. In vitro studies of Ibuprofen (Ibu) release from various LLCs allow differentiation of its release depending on the polymer content. Atomic force microscopy and contact angle methods were used to characterize the surface morphology of the hydrophobic membrane, which was used as a stratum corneum model, and also evaluate the adhesion work of the LLCs. A complex analysis of the results provided by these experimental methods allowed revealing correlations between the phase behavior and rheological characteristics of the LLCs and release kinetics of ibuprofen. The proposed biocompatible systems have considerable potential for a transdermal delivery of bioactive substances.

Fabrication and evaluation of gelatin cryogels for curcumin controlled release via transdermal iontophoresis

Transdermal drug delivery system delivers a drug through skin to the desired cells. Its use is limited due to the poor drug diffusion through the outer skin layer. The aim of this work was to fabricate and characterize the gelatin cryogel matrices for the targeted transdermal curcumin delivery via iontophoresis for the breast cancer treatment. The gelatin cryogels were fabricated at various concentrations under the freeze-drying method. FTIR, SEM, STA, and BET were utilized to characterize the gelatin cryogels and curcumin loaded gelatin cryogels. The curcumin release behavior was investigated under the effects of gelatin concentrations, electric fields, pig skin permeation, and pHs. The gelatin cryogel matrices possessed the interconnected pore sizes between 56.61 μm and 129.67 μm, in which the pore size increased with increasing gelatin concentration. The curcumin percentage released from the 1.5%v/v PSG cryogel was 89.7 %, relatively higher than the 0.8%v/v PSG cryogels. Under the effect of electric fields of 3V and 6V, the curcumin release percentages from the 1.5%v/v PSG cryogel were increased to reach 94.7 % and 96.0 %, respectively. For the release-permeation of curcumin through the pig skin, the curcumin release percentages from the 1.5%v/v PSG cryogel under the electric fields of 0V, 3V, and 6V became lower at 38.45 %, 46.33 %, and 72.33 %, respectively, as the pig skin was the obstacle in the curcumin diffusion. Slightly higher release rates and amounts of curcumin from the 1.5%v/v PSG cryogel were observed at the of pH 5.5 relative to the pH of 7.4, and at the electric field of 6V relative to 0V. The effect of applied electric field was shown to shorten the delivery time from the PSG cryogel. The 1.5%v/v PSG cryogel under applied electric field 6V was shown here as a potential biobased matrix to be used in the curcumin transdermal delivery via iontophoresis for cancer treatment.

Development of a facile, versatile and scalable fabrication approach of solid, coated, and dissolving microneedle devices for transdermal drug delivery applications

Nowadays, microneedles as novel transdermal delivery systems are interested in scientists for biomedical applications. This work aims to present a Cascade Microneedle Molding Technique (CMMT) for the reusable fabrication of polydimethylsiloxane (PDMS) molds to produce microneedle devices. To produce a positive master mold from epoxy resin, a negative PDMS mold was first fabricated. PDMS can be molded, and microneedles can be fabricated using this epoxy mold in a scalable and cost-effective manner. These molds were used to manufacture solid, coated, and dissolving microneedles, which were characterized comprehensively. Microneedle morphology and geometry were evaluated using Scanning Electron Microscopy (SEM). The mechanical integrity and ability to insert the microneedle device into the skin were assessed using compression strength analysis and force-displacement measurements. Drug penetration through animal skin was evaluated for Rhodamine B (RhB) loaded microneedles. The depth of needle insertion was also visualized using histological analysis while the spatial distribution of released cargo was determined by using confocal microscopy. Taken together, CMMT offers a simple, rapid, cost-effective, and scalable method for mass-producing microneedles with remarkable properties compared to direct 3D printing or laser ablation.

Revolutionizing Hypertension Management: Cutting-Edge Microneedle Patch Infused with Zinc Oxide Nanoparticles for Advanced Transdermal Drug Delivery

Revolutionizing Hypertension Management: Cutting-Edge Microneedle Patch Infused with Zinc Oxide Nanoparticles for Advanced Transdermal Drug Delivery

Efficacy of Transdermal Nitroglycerin Patch for the Arrest of Preterm Labor: A Retrospective Study

Efficacy of Transdermal Nitroglycerin Patch for the Arrest of Preterm Labor: A Retrospective Study

Direct 3D printing of triple-responsive nanocomposite hydrogel microneedles for controllable drug delivery

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.

Novel nano-in-micro fabrication technique of diclofenac nanoparticles loaded microneedle patches for localised and systemic drug delivery

Diclofenac, a nonsteroidal anti-inflammatory drug, is commonly prescribed for managing osteoarthritis, rheumatoid arthritis, and post-surgical pain. However, oral administration of diclofenac often leads to adverse effects. This study introduces an innovative nano-in-micro approach to create diclofenac nanoparticle-loaded microneedle patches aimed at localised, sustained pain relief, circumventing the drawbacks of oral delivery. The nanoparticles were produced via wet-milling, achieving an average size of 200 nm, and then incorporated into microneedle patches. These patches showed improved skin penetration in ex vivo tests using Franz-cell setups compared to traditional diclofenac formulations. In vivo tests on rats revealed that the nanoparticle-loaded microneedle patches allowed for quick drug uptake and prolonged release, maintaining drug levels in tissues for up to 72 h. With a systemic bioavailability of 57 %, these patches prove to be an effective means of transdermal drug delivery. This study highlights the potential of this novel microneedle delivery system in enhancing the treatment of chronic pain with reduced systemic side effects.

Integration of metformin-loaded MIL-100(Fe) into hydrogel microneedles for prolonged regulation of blood glucose levels

The transdermal drug delivery based on microneedles (MNs) provides a suitable and painless self-administration for diabetic patients. In this work, the hydrogel-forming MNs were firstly fabricated using poly(vinyl alcohol) (PVA) and chitosan (CS) as matrix. A hypoglycemic drug, metformin (Met), had been loaded into MIL-100(Fe). Then, both of free Met and Met-loaded MIL-100(Fe) were integrated into hydrogel-forming MNs for regulation of blood glucose levels (BGLs) on diabetic rats. After penetrated into the skin, the free Met could be firstly released from MNs. Due to the absorption of interstitial fluid and subsequent release of loaded Met from MIL-100(Fe), leading to a sustainable and long-term drug release behaviors. A notable hypoglycemic effect and low risk of hypoglycemia could be obtained on diabetic rat models in vivo. The as-fabricated hydrogel-forming MNs expected to become a new type of transdermal drug delivery platform for transdermal delivery of high-dose drugs to form a long-term hypoglycemic effect.