Transdermal Delivery Research Articles

Spatially Defined Post-manufacturing Loading of Nanoparticles into Hydrogel-Forming Microneedles.

Efficient transdermal delivery of the genetic material remains a key challenge for noninvasive gene therapy due to skin's barrier properties. While lipid nanoparticles (LNPs) effectively encapsulate and protect mRNA, they cannot freely penetrate the skin. Hydrogel-forming microneedle (HFMN) patches, which swell upon skin insertion, offer a promising strategy to overcome this limitation. However, integrating fragile LNPs into HFMNs without compromising the patch integrity or nanoparticle function remains an unresolved issue. Here, we present a method for the spatially controlled, post-manufacturing loading of mRNA-encapsulated LNPs into HFMN patches. Key parameters─including the HFMN patch height (250, 500, and 800 μm), insertion depth, duration (15-60 s), and repetition (up to six times)─were systematically evaluated in an agarose gel containing a dye model to optimize loading while preserving the microneedle and overall patch integrity. Under optimized conditions, 500 μm HFMN patches loaded with either MC3-DOPE-DiI-LNPs or MC3-DOPE-eGFP-LNPs, at 400 μm insertion depth and 15 s hold time, achieved up to 140 μg of payload after six insertions. Ex vivo experiments using fluorescently labeled empty LNPs confirmed the nanoparticle release. Despite modest recovery, functional studies demonstrated the successful delivery and cellular uptake of functional LNPs into human skin, as confirmed by IVIS imaging. This approach offers a robust and minimally invasive method to load and deliver the genetic material through the skin, supporting the advancement of the microneedle-based transdermal gene therapy.

Optimization of a Dissolvable Lipid Nanoparticle Microneedle Formulation for mRNA Delivery Using Design of Experiments.

Microneedles (MNs) are an emerging strategy to realize the transdermal delivery of lipid nanoparticles (LNPs) in a minimally invasive manner. Via development, the LNP's physicochemical properties, such as size and charge, and the MN's composition and fabrication procedure, must be optimized. Currently, the optimization is done through trial and error, which is heavily influenced by personal experience and preference of researchers. This study utilizes Design of Experiments (DoE) for optimizing parameters in LNP-MN fabrication to gain independence from personal experience and preference. As a proof of concept, we develop an LNP-MN device to deliver mRNA encoding green fluorescent protein (GFP). Flow cytometric analysis reveals that freshly prepared LNP-MNs achieve a transfection efficiency of 43.3% in mesenchymal stem cells, compared with 8.51% for the lipofectamine control. The LNP-MN group also provides more homogeneous transfection (99.4% GFP positive cells), while the number is only 31.0% in the lipofectamine group. mRNA-LNP-MN maintains a transfection efficiency of 22.7% after 42 days of storage at room temperature. Finally, luciferase mRNA is successfully transfected into mice by the mRNA-LNP-MN delivery system.

Transfersome enhances nail penetration of antifungal drug and photosensitizer for chemo-photodynamic therapy of onychomycosis in a novel rat model.

Transfersome enhances nail penetration of antifungal drug and photosensitizer for chemo-photodynamic therapy of onychomycosis in a novel rat model.

Harnessing The Role of Polymer in Transferosomal Gel: Unlocking New Horizons in Novel Drug Delivery System

Transferosomes represent a significant innovation in transdermal drug delivery, providing a highly adaptable and effective system for transporting therapeutic agents across the skin. Compared to traditional delivery methods, transferosomes offer enhanced skin permeability, excellent biocompatibility, improved stability, and fewer systemic side effects. Incorporating transferosomes into gel formulations further improves ease of application, patient adherence, and overall therapeutic efficacy. This review emphasizes the importance of key polymers and solvents in the formulation of transferosomes and examines their use in delivering various therapeutic agents, including antimicrobials, anti-inflammatory drugs, antihypertensives, peptides, antipsychotics, and treatments for hair loss. Ultimately, transferosomal gels present a promising and user-friendly approach for both topical and systemic drug delivery in contemporary pharmaceutical science.

Exploring transdermal SARMs exposure: Analysis of the elimination profiles and metabolism for doping control purposes.

Transdermal drug delivery has been of particular interest to pharmaceutical research for decades, but is also becoming increasingly relevant in the field of sports drug testing. As shown in the past, the (unintentional) oral ingestion of trace amounts of prohibited selective androgen receptor modulators (SARMs), e.g. due to product contamination, can lead to an adverse analytical finding (AAF) in doping controls. Another site of exposure is presented by the skin, as it provides a large surface for drug penetration. However, the extent of diffusion through various layers of the skin and into the blood vessels depends, among other things, on the physicochemical and biological properties of a substance. The objective of this project was to simulate a transdermal contamination scenario and investigate the skin penetration and subsequent metabolism of microdoses of three commonly used SARMs: LGD-4033, RAD140, and S-23. For this purpose, an administration study was conducted, in which either 10 or 50 µg of the substances were applied to the lower forearm of 5 volunteers each. The collected urine samples were analyzed via LC-MS/MS following enzymatic hydrolysis and solid-phase extraction. This methodical approach is distinguished by its high sensitivity, enabling the detection of at least 5 pg/mL for LGD-4033 and S-23. After 10 µg administration, LGD-4033 and S-23 as well as associated metabolites were detected, while RAD140 was only detected in urine samples of one subject (n = 5). Following the application of 50 µg, RAD140 was detected in all subjects (n = 5) for up to 9 days, and additional metabolites of LGD-4033 and S-23 were identified. The long-term metabolite of LGD-4033 (M5b) was detected up to 12 days after the dermal administration of 10 µg, and up to 25 days after application of 50 µg, while S-23 was traceable for up to 16 respectively 24 days. It was demonstrated for all three SARMs that they penetrate the skin and may-even in trace amounts-produce AAFs when administered transdermally. Information on urinary concentrations and metabolism following transdermal administration of SARMs may assist in the interpretation of AAFs, particularly when dermal contamination or intentional doping via the skin is discussed.

Impact of Electromagnetic Field on the Physicochemical Properties, Permeability, and Accumulation of Salicylic Acid

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

Digital Light Processing of Methacrylated Silk Fibroin Microneedles: Precision Engineering for Enhanced Transdermal Delivery and Skin Regeneration.

Despite the promising potential of digital light processing (DLP)─fabricated silk fibroin (SF) microneedles (MNs) in transdermal applications, their clinical translation faces two major challenges: insufficient manufacturing precision to achieve architectural resolution and inadequate mechanical strength to penetrate the epidermis effectively. To overcome these critical barriers, we developed a methacrylated silk fibroin (Sil-MA) bioink that combines high biocompatibility with enhanced printability. By systematically optimizing material formulation, printing parameters and MN geometry, we successfully fabricated DLP-printed Sil-MA MNs with precise architecture control and superior mechanical performance. These MNs demonstrated no cytotoxicity and enabled efficient transdermal delivery of three distinct dermatological therapeutics. Comprehensive in vitro and in vivo assessments indicated that the DLP-printed Sil-MA MNs also acted as mechanical stimulators, significantly promoting epidermal keratinocyte proliferation. This engineered platform offers a versatile strategy for developing multifunctional MN systems for therapeutic delivery and tissue engineering applications.

Sustained acoustic medicine increases local circulation with a diclofenac delivery patch: a randomized placebo controlled study

BackgroundSustained Acoustic Medicine (SAM) is a non-invasive long-term wearable device that delivers localized long duration high-frequency continuous ultrasound. SAM's biomechanical and diathermic stimuli enhance local circulation and oxygenation, accelerate tissue healing, and alleviate pain. The sonophoresis effects of SAM further improve transdermal drug delivery. Diclofenac is a topical Nonsteroidal anti-inflammatory drug for treating localized musculoskeletal (MSK) pain. Its efficacy is significantly dependent on skin porosity. This study aims to determine the diathermic effects of SAM and diclofenac on localized blood circulation.MethodsSixty-four healthy participants were randomly assigned to four groups (Active SAM group: n = 32, Placebo SAM group: n = 32): (A) Coupling gel + placebo SAM), (B) Coupling gel + active SAM, (C) 2.5% Diclofenac gel + placebo SAM, and (D) 2.5% Diclofenac gel + active SAM. Both forearms were treated with a placebo and active SAM devices for 1 h. The blood flux (perfusion units, PU) and temperature (degrees centigrade) change were recorded at 10 min intervals for 60 min using high-laser-power Doppler flowmetry. Blood circulation and temperature were recorded and reported (Clinical trial Identifier: NCT06510062).ResultsSAM increased blood flow significantly over 60 min by 19.2 PU (p < 0.0001) with coupling patch and 18.6 PU with 2.5% diclofenac patch (p < 0.0001) vs. placebo. Surface level tissue temperature increased by Δ2.4°C (p < 0.0001) with gel coupling patch and Δ2.2°C (p < 0.0001) with 2.5% diclofenac patch vs. placebo ultrasound treatment (p < 0.0001). There was no significant difference between standard coupling ultrasound gel and 2.5% diclofenac gel in blood flow and temperature. SAM provided a significant temperature increase at 20 min and a circulation increase at 10 min, which remained for the duration of the 60 min. All participants completed the study with no adverse events.ConclusionSAM treatment significantly increases local blood circulation after 10 min, increases temperature after 20 min, and sustains the effects of SAM's stimulation. The 2.5% diclofenac gel does not affect SAM's biological effects to increase local circulation. The study concludes that the application of diclofenac does not affect the diathermic properties of SAM exposure while enhancing the efficacy of diclofenac delivery through sonophoresis.Clinical Trial Registrationidentifier NCT06510062.

Topical Percutaneous Drug Delivery for Allergic Diseases: A Novel Strategy for Site-Directed Pharmacologic Modulation

Topical percutaneous drug delivery has recently emerged as a novel strategy for the treatment of allergic diseases, offering targeted drug delivery to mucosal tissues adjacent to the skin. Unlike conventional topical approaches that act on the skin surface or mucosal membranes, topical percutaneous drug delivery enables non-invasive pharmacologic modulation of deeper structures such as the conjunctiva, nasal mucosa, and trachea. This review explores the rationale, pharmacokinetic foundation, clinical data, and future prospects of transdermal therapy in allergic conjunctivitis, allergic rhinitis, and asthma-related cough. In allergic conjunctivitis, eyelid-based transdermal delivery of antihistamines such as diphenhydramine and epinastine has shown rapid and long-lasting symptom relief, with epinastine cream recently approved in Japan following a randomized controlled trial (RCT) demonstrating its efficacy. Preclinical and clinical pharmacokinetic studies support the eyelid’s unique permeability and sustained drug release profile, reinforcing its utility as a delivery site for ocular therapies. In allergic rhinitis, diphenhydramine application to the nasal ala demonstrated symptomatic improvement in patients intolerant to intranasal therapies, though anatomical separation from the inflamed turbinates may limit consistent efficacy. Similarly, cervical tracheal application of steroids and antihistamines has shown potential benefit in asthma-related cough, especially for patients refractory to inhaled treatments, despite anatomical and depth-related limitations. Overall, site-specific anatomy, skin permeability, and disease localization are critical factors in determining therapeutic outcomes. While trans-eyelid therapy is supported by robust data, studies on the nasal ala and trachea remain limited to small-scale pilot trials. No major adverse events have been reported with nasal or tracheal application, but eyelid sensitivity requires formulation caution. To validate this promising modality, further RCTs, pharmacokinetic analyses, and formulation optimization are warranted. Topical percutaneous drug delivery holds potential as a non-invasive, site-directed alternative for managing allergic diseases beyond dermatologic indications.

Impact of various electromagnetic fields on the transdermal permeability of naproxen and the effect of active compound exposure on magnetic field properties.

Impact of various electromagnetic fields on the transdermal permeability of naproxen and the effect of active compound exposure on magnetic field properties.

Feasibility of using focused acoustic vortex for enhancing transdermal delivery.

Feasibility of using focused acoustic vortex for enhancing transdermal delivery.

Development and Evaluation of an Innovative S-Flurbiprofen-Diethylamine Emulgel With Superior Transdermal Delivery and Analgesic Activity.

This study aimed to develop an innovative (S-flurbiprofen)-diethylamine (SFP-DEA) emulgel formulation via incorporating SFP as the active pharmaceutical ingredient within a carbomer 940 gel matrix. SFP-DEA emulgel was synthesized by dissolving SFP-DEA in the aqueous phase of an oil-in-water (O/W) emulsion, followed by dispersion into a carbomer 940 gel matrix. The physicochemical stability of SFP-DEA emulgel was evaluated via centrifuge, temperature swing test, high temperature, and long-term storage at ambient conditions. Exvivo SFP transdermal delivery of SFP-DEA emulgel was evaluated using a Franz diffusion cell combined with excised rat skin. The invivo analgesic activity and skin irritation test of SFP-DEA emulgel were evaluated using a mouse knee osteoarthritis model and healthy rats, respectively. Results demonstrated that SFP-DEA emulgel showed robust physicochemical stability and retain a final SFP content of 1.5% (w/w). Exvivo transdermal study demonstrated that EMG5 (the emulgel optimized with laurocapram and menthol as penetration enhancers) achieved an 8-h cumulative SFP transdermal flux of 741.28 μg/cm2 (44.23% of the administered dose), which is 27.94-fold higher than that of Loqoa (SFP tapes). In addition, SFP-DEA emulgel demonstrated rapid analgesic efficacy, with an 84.36% pain inhibition rate within 30 min in the osteoarthritis model, and elicited no signs of skin irritation in rats. In conclusion, the SFP-DEA emulgel developed herein exhibits high stability, enhanced transdermal delivery, preliminary analgesic activity, and favorable safety profiles, positioning it as a promising topical therapeutic candidate.

Polymeric porous microneedle-mediated transdermal metformin delivery system: A high-dose sustained-release platform for enhanced glycemic regulation.

Polymeric porous microneedle-mediated transdermal metformin delivery system: A high-dose sustained-release platform for enhanced glycemic regulation.

Dissolving microneedles in transdermal drug delivery: A critical analysis of limitations and translation challenges.

Dissolving microneedles in transdermal drug delivery: A critical analysis of limitations and translation challenges.

Engineering a Polyacrylamide/Polydopamine Adhesive Hydrogel Patch for Sustained Transdermal Vitamin E Delivery

A transdermal drug delivery system based on hydrogel patches was explored, leveraging their sustained release properties and biocompatibility. Despite these advantages, conventional hydrogels often lack proper adhesion to the skin, limiting their practical application. To address this issue, we designed a skin-adhesive hydrogel using a polyacrylamide (PAM)/polydopamine (PDA) dual-network structure. The matrix combines the mechanical toughness of PAM with the strong adhesive properties of PDA, derived from mussel foot proteins, enabling firm tissue attachment and robust performance under physiological conditions. To demonstrate its applicability, the hydrogel was integrated with poly(lactic-co-glycolic acid) (PLGA) nanoparticles encapsulating the hydrophobic antioxidant vitamin E as a model compound. The resulting PAM/PDA@VitE hydrogel system exhibited improved swelling behavior, high water retention, and prolonged release of α-tocopherol. These results suggest that the PAM/PDA hydrogel platform is a versatile vehicle not only for vitamin E, but also for the transdermal delivery of various cosmetic and therapeutic agents.

Transdermal drug delivery system: A comprehensive review of innovative strategies, applications, and regulatory perspectives

Transdermal drug delivery system: A comprehensive review of innovative strategies, applications, and regulatory perspectives

In-vivo Evaluation of Ultrasound Transducers with Sweep-Frequency Excitation for Noninvasive Transdermal Insulin Delivery

In-vivo Evaluation of Ultrasound Transducers with Sweep-Frequency Excitation for Noninvasive Transdermal Insulin Delivery

Formulation, development and evaluation of meclizine HCL transdermal patches

This work used a solvent evaporation approach with polyethylene glycol (PEG 400) as a plasticizer to develop a transdermal patch with meclizine Hcl using varying ratios of hydrophilic and hydrophobic polymeric systems. FT-IR spectroscopy research was used to examine the drug's and the polymers' physicochemical compatibility. The physicochemical characteristics, skin irritation, in vitro drug release, ex-vivo permeation investigations across rat abdomen skin, and stability studies of the developed patches were assessed. The medication and the polymers utilised did not interact, according to the findings of FT-IR investigations. The physicochemical parameters of each formulation were consistent. Franz diffusion cells were used to conduct in vitro permeation tests of the formulations. Formulation F3 adhered to Fick's diffusion process and demonstrated superior penetration through rat skin (8527.5±1.25µg/cm2 /hr) in comparison to the other formulations. Formulation F3, which contains the polymeric blend 19:1 Hydroxypropylmethyl Cellulose (HPMC E 50cps: Eudragit RL 100), has demonstrated optimal release when compared to other formulations and demonstrated high physical stability based on in-vitro drug release and ex-vivo skin penetration performance. Further in-vivo tests were necessary, although it has been shown that meclizine Hcl can be constructed as a matrix type transdermal drug delivery system (TDDS).

Advances in magnetic microneedles: From fabrications to applications.

Advances in magnetic microneedles: From fabrications to applications.

Enhancement of solubilization and transdermal delivery of methotrexate in microemulsions with natural deep eutectic solvents screened by COMSO-RS

Enhancement of solubilization and transdermal delivery of methotrexate in microemulsions with natural deep eutectic solvents screened by COMSO-RS