Transdermal Drug Delivery Devices Research Articles

Ambient Moisture-Driven Self-Powered Iontophoresis Patch for Enhanced Transdermal Drug Delivery.

Iontophoretic transdermal drug delivery (TDD) devices are known to enhance the transdermal transport of drugs. However, conventional transdermal iontophoretic devices require external power sources, wired connections, or mechanical parts, which reduce the comfort level for patients during extended use. In this work, a self-powered, wearable transdermal iontophoretic patch (TIP) is proposed by harvesting ambient humidity for energy generation, enabling controlled TDD. This patch primarily uses moist-electric generators (MEGs) as its power source, thus obviating the need for complex power management modules and mechanical components. A single MEG unit can produce an open-circuit voltage of 0.80V and a short-circuit current of 11.65µA under the condition of 80% relative humidity. Amplification of the electrical output is feasible by connecting multiple generator units in series and parallel, facilitating the powering of certain commercial electronic devices. Subsequently, the MEG array is integrated with the TDD circuit to create the wearable TIP. After 20 min of application, the depth of drug penetration through the skin is observed to increase threefold. The effective promotion effect of TIP on the transdermal delivery of ionized drugs is corroborated by simulations and experiments. This wearable TIP offers a simple, noninvasive solution for TDD.

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.

P‐10.10: Wearable Transdermal Drug Delivery Devices based on Piezoelectric Micropumps Integrated with Microneedles Array

P‐10.10: Wearable Transdermal Drug Delivery Devices based on Piezoelectric Micropumps Integrated with Microneedles Array

A review on transdermal drug delivery system

Drugs that are applied topically are delivered using transdermal drug delivery devices. These are pharmaceutical preparations of varying sizes, containing one or more active ingredients, intended to be applied to the unbroken skin in order to deliver the active ingredient after passing through the skin barriers, and these avoid first pass metabolism. Today about 74% of drugs are taken orally and are not found effective as desired. To improve efficacy transdermal drug delivery system was emerged. A notable advantage of transdermal drug delivery compared to other methods like oral, topical, intravenous (IV), and intramuscular (IM) administration is its controlled release of medication into the patient's system. This controlled release is achieved either by using a porous membrane enclosing a medication reservoir or by utilizing the patient's body heat to melt thin layers of medication embedded in the adhesive. Despite its benefits, transdermal drug delivery has certain limitations due to the skin's effective barrier function. Only molecules with small sizes can efficiently permeate the skin and consequently be delivered through this method.

Langmuir-Blodgett-Mediated Formation of Antibacterial Microneedles for Long-Term Transdermal Drug Delivery.

Microneedles (MNs) have become versatile platforms for minimally invasive transdermal drug delivery devices. However, there are concerns about MN-induced skin infections with long-term transdermal administration. Using the Langmuir-Blodgett (LB) technique, a simple method for depositing antibacterial nanoparticles of various shapes, sizes, and compositions onto MNs is developed. This strategy has merits over conventional dip coating techniques, including controlled coating layers, uniform and high coverage, and a straightforward fabrication process. This provides MNs with a fast-acting and long-lasting antibacterial effect. Thisstudy demonstrates that antibacterial MNs achieve superior bacterial elimination in vitro and in vivo without sacrificing payload capacity, drug release, or mechanical strength. It isbelieved that such a functional nanoparticle coating technique offers a platform for the expansion of MNs function, especially in long-term transdermal drug delivery fields.

A review on transdermal drug delivery system

In order to produce systemic effects, transdermal drug delivery systems (TDDS), commonly referred to as "patches," are dosage forms that are intended to spread a therapeutically active amount of medicine across the skin of a patient. Drugs that are applied topically are delivered using transdermal drug delivery devices. These are pharmaceutical preparations of varying sizes, containing one or more active ingredients, intended to be applied to the unbroken skin in order to deliver the active ingredient after passing through the skin barriers, and these avoid first pass metabolism. Today about 74% of drugs are taken orally and are not found effective as desired. To improve efficacy transdermal drug delivery system was emerged. In TDDS the drug easily penetrates into the skin and easily reaches the target site. To get around the problems with medicine delivery via oral route, transdermal drug delivery systems were developed. These systems have been utilized as secure and reliable drug delivery systems since 1981.

Hydroquinone cream-based polymer microneedle roller for the combined treatment of large-area chloasma

Melasma is a common hyperpigmented skin condition that occurs on the face and other areas prone to light exposure, seriously affecting people's quality of life. Microneedle, a new type of transdermal drug delivery device, can significantly improve skin permeability. In this study, we designed and fabricated a polymer microneedle roller (PMR) using a mold hot pressing method, and established a mouse model of melasma induced by ultraviolet radiation. The dynamometer and insertion test of MNs into parafilm and skin of mice indicates that the MNs have sufficient mechanical properties to insert parafilm and skin of mice. The two methods (apply hydroquinone cream (HQC) directly and pre-treat with PMR before applying HQC) were used to treat melasma. From the results of skin surface observation, determination of superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in skin and liver tissues, histological observation, and skin Optical coherence tomography (OCT), we confirmed both the two methods had a therapeutic effect while the PMR pretreatment group exhibited a better therapeutic effect. In addition, there were statistical differences between the UV group (P < 0.05). Together these results indicated that the MNs may be promising in future clinical applications in improving the UV irradiation-induced pigmentation like melisma.

Manufacturing of a Transdermal Patch in 3D Printing.

Diabetes mellitus is an endocrine disorder that affects glucose metabolism, making the body unable to effectively use the insulin it produces. Transdermal drug delivery (TDD) has attracted strong interest from researchers, as it allows minimally invasive and painless insulin administration, showing advantages over conventional delivery methods. Systems composed of microneedles (MNs) assembled in a transdermal patch provide a unique route of administration, which is innovative with promising results. This paper presents the design of a transdermal patch composed of 25 microneedles manufactured with 3D printing by stereolithography with a class 1 biocompatible resin and a printing angle of 0°. Finite element analysis with ANSYS software is used to obtain the mechanical behavior of the microneedle (MN). The values obtained through the analysis were: a Von Misses stress of 18.057 MPa, a maximum deformation of 2.179×10-3, and a safety factor of 4. Following this, through a flow simulation, we find that a pressure of 1.084 Pa and a fluid velocity of 4.800 ms were necessary to ensure a volumetric flow magnitude of 4.447×10-5cm3s. Furthermore, the parameters found in this work are of great importance for the future implementation of a transdermal drug delivery device.

Microneedles: One-Plane Bevel-Tipped Fabrication by 3D-Printing Processes.

This article presents microneedles analyses where the design parameters studied included length and inner and outer diameter ranges. A mathematical model was also used to generalize outer and inner diameter ratios in the obtained ranges. Following this, the range of inner and outer diameters was completed by mechanical simulations, ranging from 30 μm to 134 μm as the inner diameter range and 208 μm to 250 μm as the outer diameter range. With these ranges, a mathematical model was made using fourth-order polynomial regressions with a correlation of 0.9993, ensuring a safety factor of four in which von Misses forces of the microneedle are around 17.931 MPa; the ANSYS software was used to analyze the mechanical behavior of the microneedles. In addition, the microneedle concept was made by 3D printing using a bio-compatible resin of class 1. The features presented by the microneedle designed in this study make it a promising option for implementation in a transdermal drug-delivery device.

A REVIEW ON PRESENT AND FUTURE OUTLOOK OF 3D PRINTING IN TRANSDERMAL DRUG DELIVERY SYSTEMS

The suitability of different printing processes for the direct or indirect printing of microneedle arrays, as well as the modification of their surface with drug-containing coatings, has been investigated. 3D printing refers to a group of technologies that use numerically controlled apparatus to create a physical object from a virtual representation. The transdermal route has been introduced as an alternative to the bolus system. The skin is also identified to pose a barrier to permit molecules. The loss that occurred is compensated by transdermal delivery. 3D printing has several advantages in terms of waste reduction, design flexibility, and lowering the high cost. The compatibility of 3D printing techniques with printed medicine products is a factor in their selection. The variety of printable materials that are presently being used or could be utilized for 3D printing of transdermal drug delivery (TDD) devices. 3D printing has the potential to change today's "one size fits all" production and be used across the medication development process. 3D printing technology in the field of transdermal drug development as the system can be advanced in such as way that concentration can be increased or decreased with various drugs used in the printed featuring layers to enhancement of therapeutic efficacy. The impact and limitations of using 3D printing as a production process for transdermal drug delivery devices are required to be evaluated. This review discusses the present and future overlook of 3D printing technology of transdermal drug delivery systems and some advantages and disadvantages of 3D printing technology over conventional drug delivery approach.

Polysaccharide-Based Transdermal Drug Delivery.

Materials derived from natural plants and animals have great potential for transdermal drug delivery. Polysaccharides are widely derived from marine, herbal, and microbial sources. Compared with synthetic polymers, polysaccharides have the advantages of non-toxicity and biodegradability, ease of modification, biocompatibility, targeting, and antibacterial properties. Currently, polysaccharide-based transdermal drug delivery vehicles, such as hydrogel, film, microneedle (MN), and tissue scaffolds are being developed. The addition of polysaccharides allows these vehicles to exhibit better-swelling properties, mechanical strength, tensile strength, etc. Due to the stratum corneum’s resistance, the transdermal drug delivery system cannot deliver drugs as efficiently as desired. The charge and hydration of polysaccharides allow them to react with the skin and promote drug penetration. In addition, polysaccharide-based nanotechnology enhances drug utilization efficiency. Various diseases are currently treated by polysaccharide-based transdermal drug delivery devices and exhibit promising futures. The most current knowledge on these excellent materials will be thoroughly discussed by reviewing polysaccharide-based transdermal drug delivery strategies.

Ultrasound-mediated rapamycin delivery for promoting osseointegration of 3D printed prosthetic interfaces via autophagy regulation in osteoporosis

Osteoporosis-derived bone marrow mesenchymal stem cells (OP-BMSCs) have impaired cell function, low osteogenic activity, and potential osteoclast inducibility, resulting in insufficient osseointegration and increased risk of catastrophic postoperative complications after arthroplasty. The low autophagy activity of OP-BMSCs contributed to poor osseointegration, which could be regulated by the classical autophagic activator, rapamycin. Hence, it is of great significance to regulate autophagy by rapamycin to promote osseointegration at the three-dimensional (3D) printed prosthetic interfaces under osteoporotic environment. In this study, 3D printed porous titanium alloy prosthetic interfaces with bionic pore size and porosity were prepared and implanted into the distal femur of osteoporosis rabbits. Subsequently, a transdermal drug delivery device was used to deliver rapamycin to the interfaces implantation sites. Ultrasound-mediated rapamycin delivery could restore the declined cellular activities (including cell viability, proliferation, migration, and osteogenesis), as well as inhibit potential osteoclast-inducing capacity and adipogenic differentiation by upregulating the autophagy level of OP-BMSCs. Moreover, percutaneous ultrasound-mediated rapamycin delivery significantly improved bone ingrowth and osseointegration of prosthetic interfaces in osteoporotic environment. To conclude, this novel therapy combining 3D printed bionic prosthesis and percutaneous ultrasound-mediated rapamycin delivery can effectively promote prosthetic interfaces osseointegration by regulating autophagy after arthroplasty for patients with osteoporosis.

Pressure sensitive adhesives in transdermal drug delivery system

Transdermal drug delivery systems (TDDS) are used to transfer medicines into the systemic circulation through the skin. (Trans)dermal patches are well-known pharmacological formulations that are applied to the skin’s surface for a variety of reasons, ranging from treating cutaneous diseases to achieving a systemic impact. Transdermal drug delivery (TDD) devices rely heavily on adhesives. In addition to the normal functional adhesive qualities, adhesives for TDD applications must be biocompatible with the skin, chemically compatible with the medication, and enable consistent, efficient drug administration. One of the most important components of a TDDS is the pressure-sensitive adhesive (PSA). PSA’s primary role is to aid patch adherence to the skin, but it also serves as a matrix for the medication and other excipients. As a result, PSA impacts other important quality aspects of the TDDS, such as drug distribution, flux through skin, and physical and chemical stability of the completed product, in addition to patch adherence. This article addresses transdermal drug delivery systems, their benefits and drawbacks, and their uses in pharmaceuticals, as well as providing detailed information on pressure sensitive adhesives.

Effect of Mesua ferrea Linn. seed kernel oil on percutaneous absorption of Diltiazem hydrochloride through pig ear epidermis: A mechanistic study

The present study reports the mechanistic investigation on Mesua ferrea L. seed kernel oil as a natural skin permeation enhancer. The natural oil was extracted by Soxhlation method. The permeation parameters resulting from the ex vivo skin permeation study of the model drug Diltiazem HCl across oil pre-treated pig ear epidermis revealed better transdermal flux of the test groups compared to the control one. Also, the investigated oil exhibited significantly higher penetration enhancement effect compared to the standard penetration enhancer Transcutol and the maximum permeation enhancement effect was observed at 15% v/v in PG. The permeation enhancement mechanistic studies by FT-IR, DSC and SEM suggested that the enhancement effect of the oil was due to the fluidization of lipids and interaction with keratinocytes of the stratum corneum maintaining morphological integrity of the skin membrane. Furthermore, the test oil was found to be non-irritant in nature and safe for topical application. These findings suggests the Mesua ferrea L. seed oil is an efficient and safe natural skin permeation enhancer providing the scope for future research on its usage in the development of transdermal drug delivery devices.

NIR Laser‐Triggered Microneedle‐Based Liquid Band‐Aid for Wound Care

AbstractMicroneedles (MNs) have attracted widespread scientific and industrial interest in the past decade as an efficient, painless, low‐cost, and relatively safe transdermal drug delivery device. However, their drawbacks such as insufficient dose accuracy and limited penetration depth may limit the clinical applications. Here, a light‐controlled liquid band‐aid based on MNs is developed for antibacterial applications. Metal–organic framework‐derived peroxidase‐like nanozyme loaded in MNs can not only convert light energy into heat to enhance drug permeation but also decompose hydrogen peroxide into hydroxyl radicals for antibacteria. The heat generated by the nanozyme can facilitate MNs to melt and form a liquid band‐aid, which is beneficial to insulate the wound from the surrounding bacterial environment. These studies in a Staphylococcus aureus‐infected mice model also prove that this laser‐triggered liquid band‐aid can efficiently reduce skin inflammation and promote wound healing. Together, these results demonstrate that the rational design of MNs can enhance antibacterial and wound healing efficiency.

New cellulose-collagen-alginate materials incorporated with quercetin, anthocyanins and lipoic acid

Herein we present a new biomaterial based on cellulose, collagen and sodium alginate which served as a matrix for the incorporation of bioactive substances with antioxidant properties. Compared with pure cellulose hydrogels, the compressive strength and the elastic modulus of cellulose-collagen-alginate hydrogels were significantly enhanced, thus the compressive strength increased from 0.256 kPa to 6.91 kPa, while the elastic modulus increased from 0.0023 kPa to 0.115 kPa at 30% strain level. The release kinetic of all drugs through matrix components was done according to the Korsmeyer-Peppas model with a Fickian diffusion. The presence of bioactive principles, quercetin, lipoic acid and anthocyanins, gives biomaterials an antioxidant capacity on average 30% higher compared to the base matrix. The mechanical resistance, mucoadhesiveness, bioadhesiveness, release kinetic, and antioxidant capacity of active principles, recommend these biomaterials for the manufacture of transdermal drug delivery devices.

Xanthan Matrix as Drug ZDelivery System

Here we present a new drug delivery system based on xanthan esterified with acrylic acid. This material served as a matrix for the incorporation of bioactive substances with antimicrobial and anti-inflammatory properties. The materials were characterized by Fourier Transform Infrared Spectroscopy (FTIR), Nuclear Magnetic Resonance (NMR) and Scanning Electron Micrography (SEM). Mechanical strength tests showed a substantial improvement in the resilience and flexibility of the polymer matrix modified by esterification under conditions of mechanical stress. The release of bioactive substances from the basic matrix follows a Korsmeyer-Peppas type kinetics. The modified xanthan-based transport system was shown to be antimicrobially active with an inhibition rate of almost 100% on gram-positive and gram-negative bacteria. The obtained results recommend this biomaterial for the manufacture of transdermal drug delivery devices.

Sustained acousticmedicine; sonophoresis for nonsteroidal anti-inflammatory drug delivery in arthritis.

Background:Arthritis pain is primarily managed by nonsteroidal anti-inflammatory drugs (NSAIDs), such as diclofenac. Topical diclofenac gel is limited in efficacy due to its limited penetration through the skin. This study investigates the use of a multihour, wearable, localized, sonophoresis transdermal drug delivery device for the penetration enhancement of diclofenac through the skin.Materials & methods:A commercially available, sustained acoustic medicine (sam®) ultrasound device providing 4 h, 1.3 W, 132 mW/cm2, 3 MHz ultrasound treatment was evaluated for increasing the drug delivery of diclofenac gel through a human skin model and was compared with standard of care topical control diclofenac gel.Results:Sonophoresis of the diclofenac gel for 4 h increases diclofenac delivery by 3.8× (p < 0.01), and penetration by 32% (p < 0.01).Conclusion:Sustained acoustic medicine can be used as a transdermal drug-delivery device for nonsteroidal anti-inflammatory drugs.

Non-invasive drug delivery technology: development and current status of transdermal drug delivery devices, techniques and biomedical applications.

Pay-load deliveries across the skin barrier to the systemic circulation have been one of the most challenging delivery options. Necessitated requirements of the skin and facilitated skin layer cross-over delivery attempts have resulted in development of different non-invasive, non-oral methods, devices and systems which have been standardized, concurrently used and are in continuous upgrade and improvements. Iontophoresis, electroporation, sonophoresis, magnetophoresis, dermal patches, nanocarriers, needled and needle-less shots, and injectors are among some of the methods of transdermal delivery. The current review covers the current state of the art, merits and shortcomings of the systems, devices and transdermal delivery patches, including drugs' and other payloads' passage facilitation techniques, permeation and absorption feasibility studies, as well as physicochemical properties affecting the delivery through different transdermal modes along with examples of drugs, vaccines, genes and other payloads.

Design and Analyses of a Transdermal Drug Delivery Device (TD3) †.

In this paper, we introduce a novel type of transdermal drug delivery device (TD3) with a micro-electro-mechanical system (MEMS) design using computer-aided design (CAD) techniques as well as computational fluid dynamics (CFD) simulations regarding the fluid interaction inside the device during the actuation process. For the actuation principles of the chamber and microvalve, both thermopneumatic and piezoelectric principles are employed respectively, originating that the design perfectly integrates those principles through two different components, such as a micropump with integrated microvalves and a microneedle array. The TD3 has shown to be capable of delivering a volumetric flow of 2.92 × 10−5 cm3/s with a 6.6 Hz membrane stroke frequency. The device only needs 116 Pa to complete the suction process and 2560 Pa to complete the discharge process. A 38-microneedle array with 450 µm in length fulfills the function of permeating skin, allowing that the fluid reaches the desired destination and avoiding any possible pain during the insertion.