Transdermal Drug Delivery Research Articles

Immunoglobulin free light chain-kappa, a novel biomarker of inflammation and cardiovascular risk, decreases after smoking cessation in association with NT-proBNP

Abstract Introduction Inflammation plays an important role in the development and progression of cardiovascular diseases. Unhealthy diet, infection, and smoking coupled with genetic factors induce inflammation in the heart and blood vessels by activating nuclear factor kappa B, which regulates the transcription of immunoglobulin free light chain (FLC)-κ in B-cells and the production of multiple inflammatory molecules. FLCs are novel biomarkers of inflammation, and their levels are associated with overall mortality in a general population and with cardiovascular outcomes. Purpose This study aimed to investigate the effect of smoking cessation (SC) on levels of FLCs as well as of the inflammation and heart failure markers. Methods Inclusion criterion was first-visit smokers with desire to quit smoking at our outpatient clinic. Smoking patients with nicotine dependence were treated with transdermal nicotine patches or orally administrated varenicline. Various clinical parameters, including inflammatory markers such as FLC levels, were measured on their first visit to our outpatient clinic for SC and after 3 months of successful and unsuccessful SC. Paired t-test or Wilcoxon signed-rank test was performed to evaluate changes in these parameters before and after SC. Results Out of 96 patients who participated in this study, 76 patients (55 males and 21 females) succeeded in SC over a period of 3 months. Body mass index (BMI) significantly increased from baseline to 3 months after initiating SC (from 23.8 to 24.2, p=0.004) in patients with successful SC. On the other hand, levels of various inflammatory markers; FLC-κ, FLC-κ/FLC-λ, and the neutrophil-to-lymphocyte ratio) significantly decreased from baseline to 3 months (from 27.5 to 24.7 mg/L, p = 0.042; from 1.2 to 1.2 mg/L, p = 0.010; and from 2.0 to 1.9, p = 0.024, respectively). In contrast, no significant changes occurred in these parameters among patients with unsuccessful SC. Percent changes of FLC-κ levels from baseline to 3 months were significantly correlated with those of CRP (r=0.217, p=0.034) and NT-proBNP (r=0.335, p<0.001) levels. Conclusion The FLC-κ level, a novel inflammatory and cardiovascular risk biomarker, decreased in smoking patients after their SC despite the increase in body weight, suggesting that the beneficial effect of SC overcomes potential risks by body weight increase. The results also suggest that a decrease in the FLC-κ level after SC is associated with a reduction of load on the heart as well as decrease in inflammation.

Nanocarrier-Based Transdermal Drug Delivery Systems for Dermatological Therapy

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

Perspective: Materials and Electronics Gaps in Transdermal Drug Delivery Patches

Abstract Transdermal drug delivery systems offer a noninvasive method of delivering drugs through the skin surface, which circumvents problems associated with metabolic breakdown, uncontrollable biodistribution after initial drug administration, and limited patient compliance. The most common implement for transdermal drug delivery is the transdermal patch (TDP), which are flexible, medicated adhesive patches that can be placed on any available skin surface for targeted delivery. In this perspective, we summarize the most recent advancements in transdermal drug delivery patches and highlight gaps that can be filled with advanced sensor development.

Transforming Biologics Delivery through Microneedles

This review explores the potential of microneedles (MNs) in enhancing the delivery of biologics vital for treating conditions, including infectious diseases, cancer, and autoimmune disorders. The COVID-19 pandemic has amplified the demand for biologics, prompting research and development. The global biologics market is expected to grow substantially due to the rise of personalized medicine. Large, complex molecules, including proteins, peptides, and vaccines, are known as biologics, and a potential technique for their delivery is microneedles. MNs come in various forms: solid, hollow, coated, dissolvable, and hydrogel MNs. Traditional drug delivery methods have limitations, while transdermal drug delivery via Microneedles offers a promising alternative. Microneedles painlessly penetrate the skin's barrier, forming temporary microchannels for effective medication administration. This minimally invasive, self-administered technique increases patient comfort and compliance and eliminates the complications of oral medications and injections, indicating a bright future for biologic drug administration. Microneedles hold the promise to reshape healthcare delivery by facilitating broader access to vaccines, insulin, and other crucial biologics.

Comparison of the Efficacy of Transdermal Buprenorphine Versus Ketoprofen Patches for Post-operative Analgesia in Total Knee Arthroplasty: A Randomised Controlled Trial

Comparison of the Efficacy of Transdermal Buprenorphine Versus Ketoprofen Patches for Post-operative Analgesia in Total Knee Arthroplasty: A Randomised Controlled Trial

Application of high-polarity hydroxyl polyacrylate pressure sensitive adhesive in rizatriptan transdermal drug delivery patch

This study aimed to design a rizatriptan (RIZ) transdermal patch by combining of high-polarity hydroxyl pressure sensitive adhesive (PSA) AAOH-45 with an ion-pair strategy and investigate the molecular mechanism of high content hydroxyl PSA to enhance drug-PSA miscibility. RIZ free base, ion-pair complexes and PSAs containing hydroxyl group were prepared and characterized. Formulation factors including counter-ions, PSAs, drug-loading and others were optimized through single-factor studies and evaluated through pharmacokinetic studies and skin irritation tests. The properties of high polarity PSA and molecular mechanism of drug-PSA miscibility were investigated through molecular simulation, FTIR spectra, 13C NMR spectra, DSC, and rheology study. The optimized formulation contained 20 % (w/w) RIZ-OA (Rizatriptan-Oleic acid), 80 % AAOH-45 (w/w) as the matrix, and had a thickness of 90 μm. Compared with the oral group (MRT0-t = 5.96 ± 0.97 h) and the control patch group (MRT0-t = 11.30 ± 1.78 h), the pharmacokinetic behavior of the optimization group demonstrated sustained drug delivery behavior (MRT0-t = 20.21 ± 0.61 h) with no irritation phenomenon. The miscibility of RIZ with PSAs was positively correlated with the mass percentage of 2-HEA. Higher polar similarity, lower flowability, and stronger intermolecular interaction were responsible for the higher compatibility of high hydroxyl PSA with the drug. This study provided a reference for increasing the drug-loading in PSA and developing RIZ patch.

Recent Innovations and Future Perspectives in Transferosomes for Transdermal Drug Delivery in Therapeutic and Pharmacological Applications.

There have been several non-invasive administrations that have emerged recently to replace conventional needle injections. With its minimal rejection rate, remarkable ease of administration, and remarkable patient comfort and perseverance, the transdermal drug delivery system (TDDS) is the most attractive of them all. The skincare industry, which includes cosmetics, may also find use for TDDS in addition to the pharmaceutical industry. As this strategy mainly entails local drug administration, it can prevent untargeted drug delivery to tissues not intended for the treatment and buildup of localized drug concentrations. Transdermal delivery is hampered by a number of physicochemical characteristics of the skin, which have led to a great deal of research into ways to get over these barriers. The majority of transdermal medicines that have proved effective do so by using smaller lipophilic compounds, which have a molecular weight of a few 100 Daltons. Transferosomes have proven to be an effective method for transdermal distribution of a range of therapies, including hydrophilic actives, bigger molecules, peptides, proteins, and nucleic acids, in order to get around the medications' size and lipophilicity limits. Because of their flexible form and increased surface hydrophilicity, transferosomes are essential for the delivery of medicines and other solutes through and into the skin by exploiting hydration gradients a source of energy. As a result, the medication is released into the skin layers under regulated conditions and has improved overall penetration. In this section we outline the development of transferosomes from liposomes and solid lipid nanoparticles, as well as their subsequent advancements as commercially available dosage forms, physical-chemical characteristics, and cutaneous kinetics.

Hyaluronic acid dissolving microneedle patch-assisted acupoint transdermal delivery of triptolide for effective rheumatoid arthritis treatment

Triptolide (TP), a major active component of the herb Tripterygium wilfordii Hook F, has been shown excellent pharmacological effects on rheumatoid arthritis. However, TP is prone to causing severe organ toxicity, which limits its clinical application. In recent years, microneedle technology has provided a new option for the treatment of arthritis due to its advantages of efficient local transdermal drug delivery. In this study, we constructed a microneedle platform to deliver TP locally to the joints, thereby enhancing TP penetration and reducing systemic toxicity. Additionally, we investigated whether acupoint drug delivery can produce a synergistic effect of needles and drugs. First, TP was loaded into microneedles using polyvinylpyrrolidone and hyaluronic acid as matrix materials. Next, we established a rat adjuvant-induced arthritis (AIA) model to evaluate the therapeutic effect of TP-loaded microneedles. The experiments showed that TP-loaded microneedles alleviated the AIA rats’ inflammatory response, joint swelling, and bone erosion. However, there was no significant difference in the therapeutic effect observed in the acupoint and non-acupoint administration groups. In conclusion, TP-loaded microneedles have the advantages of safety, convenience, and high efficacy over conventional administration routes, laying a foundation for the transdermal drug delivery system-based treatment of rheumatoid arthritis.

Comparative evaluation of analgesic efficacy of buprenorphine transdermal patch and fentanyl transdermal patch in the management of postoperative pain after lower limb surgery

Background: Postoperative pain represents a significant medical issue that needs immediate attention. Despite advancements in pain management, managing postoperative pain remains challenging. Transdermal drug delivery systems (TDDS) offers a straightforward, reliable, non-invasive, and patient-friendly approach for alleviating post-surgical pain. Hence, this study was planned to evaluate the analgesic efficacy of buprenorphine and fentanyl transdermal patch in the management of post-operative pain after lower limb surgery. Methods: In this prospective, randomised study, 82 adult patients of either sex undergoing elective lower limb surgery were randomly allocated into two groups- Group A (Transdermal Buprenorphine 20 mg patch) and Group B (Transdermal Fentanyl 50 mcg patch). Postoperative pain was assessed by 10-point Visual Analogue Scale (VAS) every 6 hours following surgery on the first day and then daily for next 4 days. All patients were also monitored for total rescue analgesic requirement, drug-related adverse effect and haemodynamic status. Statistical analysis was carried out using student t-test and Chi-square test. A p-value <0.05 was considered significant. Results: The mean pain intensity scores were found to be significantly different (p<0.0001) between the two groups, with VAS scores consistently lower in Buprenorphine group as compared to Fentanyl group. Also, Buprenorphine group had the lowest demand for rescue analgesic, with 58.5% of patients requiring two administrations and 36.6% needing only one. Patients belonging to Fentanyl group exhibited higher occurrence of nausea (46.3%), vomiting (46.3%) and pruritus (31.7%). Conclusions: Our study concludes that transdermal patch of buprenorphine demonstrates superior efficacy and safety profile as compared to fentanyl patch for post-operative pain management in lower limb surgeries.

Implantable Microarray Patch: Engineering at the Nano and Macro Scale for Sustained Therapeutic Release via Synthetic Biodegradable Polymers

AbstractTransdermal drug delivery has been an increasingly studied alternative drug administration route owing to the large surface area of the skin, enabling ease of access and application. Among the various transdermal drug delivery technologies that have been developed so far, microarray patches (MAPs) incorporating microneedle technology (MN) have garnered much attention. MAPs can easily penetrate the stratum corneum, facilitating the delivery of desired substances directly into the skin, exhibiting a higher delivery efficiency compared to alternative transdermal drug delivery approaches. The effectiveness of MAPs in delivering therapeutics is affected by a multitude of factors, one of which is the selection of materials employed in their fabrication. Among various materials that have been used to fabricate MAPs, synthetic biodegradable polymers such as poly(lactic‐co‐glycolic acid) (PLGA) and polylactic acid (PLA) have been exploited for sustained and controlled release with excellent biocompatibility. PLGA and PLA can be used to construct the entire needle shaft or drug‐loaded microparticles which are then incorporated into needle layer. The combination of MN technology in conjunction with biodegradable polymers has revolutionized sustained and controlled transdermal delivery of small and large molecules.

Comparison of Combined Oral Contraceptives and a Transdermal Estrogen Patch With Oral Progesterone: Treatment of Abnormal Uterine Bleeding in Adolescents

Comparison of Combined Oral Contraceptives and a Transdermal Estrogen Patch With Oral Progesterone: Treatment of Abnormal Uterine Bleeding in Adolescents

Development of a Bentonite Nanoparticle-Based Transdermal Drug Delivery System for Burn Wound Infection Prevention

Development of a Bentonite Nanoparticle-Based Transdermal Drug Delivery System for Burn Wound Infection Prevention

Iontophoresis and electroporation-assisted microneedles: advancements and therapeutic potentials in transdermal drug delivery.

Transdermal drug delivery (TDD) using electrically assisted microneedle (MN) systems has emerged as a promising alternative to traditional drug administration routes. This review explores recent advancements in this technology across various therapeutic applications. Integrating iontophoresis (IP) and electroporation (EP) with MN technology has shown significant potential in improving treatment outcomes for various conditions. Studies demonstrate their effectiveness in enhancing vaccine and DNA delivery, improving diabetes management, and increasing efficacy in dermatological applications. The technology has also exhibited promise in delivering nonsteroidal anti-inflammatory drugs (NSAIDs), treating multiple sclerosis, and advancing obesity and cancer therapy. These systems offer improved drug permeation, targeted delivery, and enhanced therapeutic effects. While challenges remain, including safety concerns and technological limitations, ongoing research focuses on optimizing these systems for broader clinical applications. The future of electrically assisted MN technologies in TDD appears promising, with potential advancements in personalized medicine, smart monitoring systems, and expanded therapeutic applications.

Nanomaterial-Enhanced Microneedles: Emerging Therapies for Diabetes and Obesity.

Drug delivery systems (DDS) have improved therapeutic agent administration by enhancing efficacy and patient compliance while minimizing side effects. They enable targeted delivery, controlled release, and improved bioavailability. Transdermal drug delivery systems (TDDS) offer non-invasive medication administration and have evolved to include methods such as chemical enhancers, iontophoresis, microneedles (MN), and nanocarriers. MN technology provides innovative solutions for chronic metabolic diseases like diabetes and obesity using various MN types. For diabetes management, MNs enable continuous glucose monitoring, diabetic wound healing, and painless insulin delivery. For obesity treatment, MNs provide sustained transdermal delivery of anti-obesity drugs or nanoparticles (NPs). Hybrid systems integrating wearable sensors and smart materials enhance treatment effectiveness and patient management. Nanotechnology has advanced drug delivery by integrating nano-scaled materials like liposomes and polymeric NPs with MNs. In diabetes management, glucose-responsive NPs facilitate smart insulin delivery. At the same time, lipid nanocarriers in dissolving MNs enable extended release for obesity treatment, enhancing drug stability and absorption for improved metabolic disorder therapies. DDS for obesity and diabetes are advancing toward personalized treatments using smart MN enhanced with nanomaterials. These innovative approaches can enhance patient outcomes through precise drug administration and real-time monitoring. However, widespread implementation faces challenges in ensuring biocompatibility, improving technologies, scaling production, and obtaining regulatory approval. This review will present recent advances in developing and applying nanomaterial-enhanced MNs for diabetes and obesity management while also discussing the challenges, limitations, and future perspectives of these innovative DDS.

Atorvastatin loaded glycerosomal patch as an effective transdermal drug delivery: optimization and evaluation.

Aim: The study explores glycerosomes as effective vesicular systems for transdermal delivery of atorvastatin (ATO) to overcome drawbacks related to its oral administration.Methodology: The objectives of this study were to formulate, by thin-film hydration method, optimize using definitive screening design and evaluate ATO-loaded glycerosomes (ATOG) which were then incorporated into patch followed by the evaluation of glycerosomes containing different concentration of glycerol.Results & discussion: Vesicle size, Polydispersity index (PDI), zeta potential, entrapment efficiency and loading capacity of spherical ATOG (0-30%w/w) showed 137.3-192d.nm, 0.292-0.403, -3.81 to-6.76mV, 80.03-92.77% and 5.80-6.40%, respectively. In-vitro release study showed sustained release, increased skin permeability and better cell viability than pure drug. ATOG patches showed greater skin permeability than pure drug and ATO-liposomal patches.Conclusion: The study concludes that ATOGs are promising for effective transdermal delivery.

Combining ion-pair strategy and percutaneous permeation enhancers to develop sustained-release paliperidone patch

In this study, a sustained-release paliperidone (PAL) patch was developed using a combination of ion-pair strategy and percutaneous permeation enhancers (PPEs). The ion-pair strategy was used to improve drug-adhesive miscibility and control drug release. PPEs were used to break SC barrier function to facilitate drug skin permeation. The in vitro skin permeation experiments using single-factor experiments and Box-Behnken design gave the optimized formulation, a 55 μm adhesive thickness patch with 7 % (w/w) PAL-LA (Lauric acid), 9.7 % (w/w) Plurol® Oleique CC 497 (POCC). Moreover, the pharmacokinetic study confirmed its potential in sustained-release transdermal patch with longer MRT0-t (18.35 ± 3.11 h) and higher BA (63.14 %) than the gavage group (Cmax = 6.64 ± 2.61 μg/mL, MRT0-t = 2.88 ± 1.06 h, BA = 45.70 %) without significant increasing Cmax. The mechanism study revealed that forming ion-pairs effectively modulated drug’s physicochemical properties and doubly ionic H-bond strength to improve drug miscibility in patches. To summarize, a sustained-release patch of PAL was successfully developed, which provided a strategy for sustained-release patches with good drug-polymer miscibility, drug controlled-release, and feasible drug utilization features.

Immunomodulatory microneedle patch for enhanced Ferroptosis and immunogenic cell death in postoperative tumor therapy

Microneedle technologies have emerged as a promising transdermal drug delivery platform for postoperative tumor therapy. Despite their potential, enhancing intracellular drug delivery to tumor cells and boosting the therapeutic efficiency of microneedles pose significant challenges. Herein, we develop a nanomedicine-loaded microneedle to enhance the induction of ferroptosis and immunogenic cell death for postoperative tumor therapy. This advancement is achieved by pre-formulating small molecule drugs with transition metal and protein templates into nanomedicine. Upon insertion into the tumors, the microneedle rapidly dissolves, facilitating the release and subsequent cellular uptake of the nanomedicine by tumor cells. Notably, the nanomedicine can release Mn ions and ferroptosis-inducer sulfasalazine (SAS) under acidic conditions. Furthermore, the released Mn ions can produce reactive oxygen species, which decrease the levels of glutathione (GSH) and glutathione peroxidase 4 (GPX4) with increased lipid peroxidation and enhanced induction of ferroptosis. Besides, the treatment stimulates immunogenic cell death through the cell surface exposure of calreticulin (CRT) and release of high-mobility group box 1 (HMGB1), which further stimulates dendric cell maturation, T cell infiltration, and macrophage polarization towards the M1 phenotype. Consequently, this strategy significantly inhibits postoperative tumor regrowth and extends overall survival. Our study indicates the potential of the combination of nanomedicine and microneedle to improve postoperative therapeutic efficiency.

Association between treatment response and dose of blonanserin transdermal patch in patients with acute schizophrenia: A post hoc cluster analysis based on baseline psychiatric symptoms.

To explore the optimal dose of blonanserin transdermal patch (BNS-P) based on baseline psychiatric symptomatic characteristics during acute schizophrenia. A post hoc cluster analysis was conducted using data from a 6-week randomized, double-blind, placebo-controlled study of BNS-P (40 or 80 mg/day) in acute schizophrenia. We classified patients into three clusters based on baseline psychiatric symptoms. Efficacy was assessed using the change from baseline to week 6 in the PANSS total score. Safety was assessed by the incidence of adverse events. Among 577 patients, three clusters were identified, characterized by severe psychiatric (Cluster-S; n = 122), predominant negative (Cluster-N; n = 191), and predominant positive (Cluster-P; n = 264) symptoms. In Cluster-P, both BNS-P 40 and 80 mg/day reduced PANSS total score significantly more than placebo (p = 0.036, effect size = 0.342; p < 0.001, effect size = 0.687, respectively). In Cluster-S and -N, only BNS-P 80 mg/day reduced PANSS total score significantly more than placebo (p = 0.045, effect size = 0.497; p = 0.034, effect size = 0.393, respectively). The effect size was greater at 80 mg/day than at 40 mg/day across all clusters. The most common treatment-emergent adverse events were akathisia and skin-related adverse events in all clusters. BNS-P exhibited a dose-dependent antipsychotic effect in all clusters, particularly highlighting its efficacy in patients with predominant positive symptoms, even at lower doses. These findings provide novel and valuable insights for determining BNS-P dose tailoring to individual symptomatic characteristics in real-world practice.

An Integrated Microcurrent Delivery System Facilitates Human Parathyroid Hormone Delivery for Enhancing Osteoanabolic Effect.

Human parathyroid hormone (1-34) (PTH) exhibits osteoanabolic and osteocatabolic effects, with shorter plasma exposure times favoring bone formation. Subcutaneous injection (SCI) is the conventional delivery route for PTH but faces low delivery efficiency due to limited passive diffusion and the obstruction of the vascular endothelial barrier, leading to prolonged drug exposure times and reduced osteoanabolic effects. In this work, a microcurrent delivery system (MDS) based on multimicrochannel microneedle arrays (MMAs) is proposed, achieving high efficiency and safety for PTH transdermal delivery. The internal microchannels of the MMAs are fabricated using high-precision 3D printing technology, providing a concentrated and safe electric field that not only accelerates the movement of PTH but also reversibly increases vascular endothelial permeability by regulating the actin cytoskeleton and interendothelial junctions through Ca2+-dependent cAMP signaling, ultimately promoting PTH absorption and shortening exposure times. The MDS enhances the osteoanabolic effect of PTH in an osteoporosis model by inhibiting osteoclast differentiation on the bone surface compared to SCI. Moreover, histopathological analysis of the skin and organs demonstrated the good safety of PTH delivered by MDS in vivo. In addition to PTH, the MDS shows broad prospects for the high-efficiency transdermal delivery of macromolecular drugs.

Microorganism microneedle micro-engine depth drug delivery

As a transdermal drug delivery method, microneedles offer minimal invasiveness, painlessness, and precise in-situ treatment. However, current microneedles rely on passive diffusion, leading to uncontrollable drug penetration. To overcome this, we developed a pneumatic microneedle patch that uses live Enterobacter aerogenes as microengines to actively control drug delivery. These microbes generate gas, driving drugs into deeper tissues, with adjustable glucose concentration allowing precise control over the process. Our results showed that this microorganism-powered system increases drug delivery depth by over 200%, reaching up to 1000 μm below the skin. In a psoriasis animal model, the technology effectively delivered calcitriol into subcutaneous tissues, offering rapid symptom relief. This innovation addresses the limitations of conventional microneedles, enhancing drug efficiency, transdermal permeability, and introducing a creative paradigm for on-demand controlled drug delivery.