Dissolving Microneedle Patch Research Articles

FABRICATION AND CHARACTERIZATION OF DISSOLVING MICRONEEDLE PATCH USING 3D PRINTED MASTER

Objective: The purpose of this study was to fabricate a dissolving microneedle patch using a 3D-printed master and characterize it using various techniques. Methods: Dissolving microneedle patches were developed using Computer-Aided Design (CAD) software and 3D printing. Polydimethylsiloxane (PDMS) reverse molds were cast from the 3D-printed masters and filled with a solution of 20% Chitosan Oligosaccharide (COS) and 20% Polyvinyl Alcohol (PVA). The patches were dried at room temperature and characterized using Scanning Electron Microscopy (SEM), Attenuated Total Reflectance-Fourier Transform Infrared Spectroscopy (ATR-FTIR), X-ray diffraction (XRD), Thermogravimetric Analysis (TGA), Differential Scanning Calorimetry (DSC), and in vitro skin penetration studies. Results: Optical microscopy and SEM images showed the formation of a uniform microneedle. The peak at 1248 cm⁻¹ in the ATR-FTIR spectrum indicates the formation of cross-links between certain PVA radical groups and COS. XRD revealed that both polymers blended well and showed partial crystallinity, with peaks at 2θ = 11.39°, 2θ = 20°, and 2θ = 41°. DSC and TGA analyses revealed that the blend could withstand high temperatures with good stability at temperatures up to 200 °C. In vitro skin penetration studies confirmed that microneedles could successfully penetrate the skin, indicating their potential for effective transdermal drug delivery. Conclusion: This study demonstrated that COS/PVA dissolving microneedles fabricated using 3D printing and micro-molding have significant potential for transdermal drug delivery.

A dissolving microneedle patch loaded with plumbagin/hydroxypropyl-β-cyclodextrin inclusion complex for infected wound healing

Treating infected wounds is facing a serious challenge due to the rapid spread of antibiotic resistance worldwide. In the search for novel antimicrobial drugs, natural products often serve as a crucial resource. Plumbagin (PLB) is the most important natural active ingredient in the root of Plumbago zeylanica L. known for its excellent antibacterial ability. However, the application of PLB is limited because of its poor water solubility, instability, and tendency to sublimate. In this study, we propose a solution by designing a hyaluronic acid (HA)/polyvinylpyrrolidone (PVP) dissolving microneedle patch loaded with PLB/hydroxypropyl-β-cyclodextrin (HP-β-CD) inclusion complex. PLB was encapsulated into the cavity of HP-β-CD to improve its solubility and stability using the neutralization agitation method. The formation of the inclusion complex significantly increased the water solubility of PLB to 1350 ± 6.8 μg/mL, which is 17 times higher than its original value of 79.3 ± 1.7 μg/mL. The encapsulation efficiency was found to be 94.82 ± 3.34%. In vitro drug release studies, PLB microneedles loaded with PLB/HP-β-CD inclusion complex rapidly released into PBS within 15min. Furthermore, the PLB microneedles exhibited strong antibacterial activity against Staphylococcus aureus (S. aureus) both in vivo and in vitro. They also remarkably accelerated the healing of infected wounds in mice by enhancing collagen deposition and re-epithelialization, reducing inflammation, and stimulating angiogenesis. Overall, this multifunctional microneedle patch shows promising potential for clinical applications in the healing of infected wounds.

Facile minocycline deployment in gingiva using a dissolvable microneedle patch for the adjunctive treatment of periodontal disease

AbstractMinocycline is a commonly used drug for adjunctive therapy in periodontal disease. However, the current mainstream local medications primarily rely on intra‐pocket administration, which, while avoiding the side effects of traditional systemic drugs, presents challenges such as inconvenience, discomfort, and the need for professional assistance, thus affecting patient compliance. Herein, we introduce a minocycline‐loaded dissolvable microneedle (Mino‐DMN) patch that allows for local and efficient delivery of minocycline to gingiva for the treatment of periodontitis. A two‐step casting micro‐molding process involving vacuum drying and freeze drying is employed to concentrate minocycline in the microneedle part and limit its diffusion into the patch backing. The resulting Mino‐DMN patch features an array of minocycline‐enriched gelatin MNs with a porous HA patch backing. The microneedles can penetrate into gingiva with enough mechanical strength and quickly release minocycline into the gingival tissue, ensuring prolonged local residence of the drug and minimizing its loss to saliva. In vivo experiments show Mino‐DMN inhibits pro‐inflammatory factors, promotes anti‐inflammatory factors, and stimulates bone formation, surpassing topical application and comparable to the inconvenient and discomfort administration of Periocline®. This proposed Mino‐DMN offers a simple, efficient, user‐friendly strategy for the adjunctive treatment of periodontal disease.

Dissolving microneedle patches for delivery of amniotic mesenchymal stem cell metabolite products for skin regeneration in UV-aging induced mice

Microneedles offer a promising solution to enhancing dermal delivery of amniotic mesenchymal stem cell metabolite product (AMSC-MP), which contains hydrophilic protein components with high molecular weight, for the purposes of skin rejuvenation and improving human health. This study aimed to evaluate the physicochemical characteristics and in vivo efficacy of AMSC-MP-loaded microneedle patches for effectively regenerating skin tissues in UV-aging induced mice. Dissolving microneedle patches, composed of polyvinyl alcohol with an MW of 9–10 kDa and polyvinylpyrrolidone with an MW of 56 kDa, were fabricated using the double-casting method at three AMSC-MP concentrations: i.e., 30 % (MN30), 25 % (MN25), and 20 % (MN20). The microneedles patches were then evaluated for morphological, mechanical resistance, and insertion properties. An ex vivo release study was also conducted using the Franz cell method, and in vivo efficacy and irritation were then determined through collagen density scores, fibroblast cell counts, and skin irritation studies of UV-aging induced mice. The AMSC-MP microneedles displayed a pyramidal shape with 500 µm sharp tips. Mechanical testing revealed that MN30 achieved its deepest insertion into Parafilm® M (447.44 ± 37.21 µm), while MN25 achieved its deepest insertion into full-thickness porcine skin (717.92 ± 25.40 µm). The study revealed a controlled EGF release for up to 24 h, with MN20 exhibiting the highest deposition (55.94 ± 12.34 %). These findings demonstrate the successful penetration of microneedles through the stratum corneum and viable epidermis. Collagen density scores and fibroblast cell counts were significantly higher in all microneedle formulations than the control, with MN30 having the highest values. Inflammatory cell counts indicated minimal presence suggesting non-irritation in the in vivo study. Dissolving microneedle patches exhibited favorable characteristics and efficiently delivered AMSC-MP with minimal potential for irritation, providing potential technology for delivering biological anti-aging agents for the purposes of fostering skin regeneration.

Emerging Trends in Dissolving-Microneedle Technology for Antimicrobial Skin-Infection Therapies.

Skin and soft-tissue infections require significant consideration because of their prolonged treatment duration and propensity to rapidly progress, resulting in severe complications. The primary challenge in their treatment stems from the involvement of drug-resistant microorganisms that can form impermeable biofilms, as well as the possibility of infection extending deep into tissues, thereby complicating drug delivery. Dissolving microneedle patches are an innovative transdermal drug-delivery system that effectively enhances drug penetration through the stratum corneum barrier, thereby increasing drug concentration at the site of infection. They offer highly efficient, safe, and patient-friendly alternatives to conventional topical formulations. This comprehensive review focuses on recent advances and emerging trends in dissolving-microneedle technology for antimicrobial skin-infection therapy. Conventional antibiotic microneedles are compared with those based on emerging antimicrobial agents, such as quorum-sensing inhibitors, antimicrobial peptides, and antimicrobial-matrix materials. The review also highlights the potential of innovative microneedles incorporating chemodynamic, nanoenzyme antimicrobial, photodynamic, and photothermal antibacterial therapies. This review explores the advantages of various antimicrobial therapies and emphasizes the potential of their combined application to improve the efficacy of microneedles. Finally, this review analyzes the druggability of different antimicrobial microneedles and discusses possible future developments.

Silencing siRNA microneedle patches versus silicone sheets in reducing post-surgical scars: a randomized single-blinded intra-individually controlled clinical trial.

A common complication of wounds is exuberant growth of fibrotic scar tissue, which can lead to hypertrophic scars or keloids. There are currently no treatments with good evidence for preventing excessive scar tissue formation. In this study, we explored the use of microneedle patches containing siRNA inhibiting SPARC mRNA in reducing the volume of post-surgical scars. We aim to compare the differences in the volume of post-surgical scars between daily application of siRNA-embedded dissolving microneedle patches and silicone sheets. The primary study outcome measure was the 3D volume of scar elevation.Our hypothesis was that scar formation in the half of the wound treated with siRNA microneedle patches will be lesser, as reflected by a smaller 3D volume, as compared to the half treated with silicone sheets. This was an 8-week, single-blinded intra-individually controlled randomised trial in a tertiary dermatological centre. Patients with two-week-old post-operative wounds were recruited. Each half of the scar was randomly assigned to the microneedle patch or silicone sheet. Three-dimensional (3D) volumes were obtained from the scars via a high-resolution scanner at day 0, 30 and 60. At day 30, scars treated with the microneedle patches had a lower geometric mean volume of 0.79mm3 when compared to scars treated with silicone sheets, with a difference in mean percentage volume reduction of 10.70%.At day 60, scars treated with the microneedle patches had a statistically significant lower volume (8.88mm3) when compared to the side treated with silicone sheets (12.77mm3, p=0.005), with a difference in mean percentage reduction of 9.66%. Additionally, there was also a statistically significant difference between the percentage reduction in scar volume, compared to baseline, on the side treated with microneedle patches (mean=83.78%) compared to the side treated with silicone sheets (mean=74.11%). There was a significantly greater reduction in the volume of post-surgical scars on the side treated with microneedle patches compared to the side treated with silicone sheets. This demonstrates the use of transdermal gene silencing technology for scar inhibition and that siRNA microneedle patches can be an effective and safe modality in the reduction of scar tissue formation. Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12622000558729, https://www.anzctr.org.au.

A transdermal delivery system using microneedle patches containing poly(lactic-co-glycolic)-encapsulated acitretin nanoparticles for topical and extended treatment

Acitretin is a primary treatment for moderate-to-severe psoriasis, however, the substantial side effects associated with its daily oral administration and relapse after withdrawal significantly restrict its clinical utility. To address this challenge, we designed a transdermal delivery system using hyaluronic acid-based dissolving microneedle patches containing poly (lactic-co-glycolic)-encapsulated acitretin nanoparticles for effective topical drug administration and prolonged therapeutic effects. This microneedle exhibited favorable mechanical properties, which could easily penetrate through the thickened epidermis for intralesional drug delivery. We showed that numbers of acitretin-loaded microspheres were uniformly compacted at the bottom of needle tips, giving the microneedle dense surface morphology required for effective skin penetration, prolonged retention, and sustained release of acitretin both in vitro and in an imiquimod-induced psoriasis in vivo model. A single dose of our transdermal treatment not only alleviated the psoriasis-like skin inflammation in acute phase, but also established a long-term therapeutic effect. Moreover, the transdermal approach proved more effective than daily oral administration of the same dose of free drug, demonstrating less systemic toxicity than oral drug intake or topical cortisol application. This new system offers an innovative way for drug delivery and disease treatment, and also provides an antimicrobial control strategy for a wide range of applications.

Enhanced Transdermal Delivery of Rhein In Vitro Using a Dissolving Microneedle Patch

Enhanced Transdermal Delivery of Rhein In Vitro Using a Dissolving Microneedle Patch

Dissolving Microneedles Patch: A Promising Approach for Advancing Transdermal Delivery of Antischizophrenic Drug

ObjectiveMicroneedles (MNs) are minimally invasive transdermal drug delivery systems capable of penetrating the stratum corneum to overcome the barrier properties. The primary objective of this research was to prepare dissolving microneedle patches (DMNP) loaded with quetiapine (QTP). MethodsDMNP were fabricated employing the solvent casting technique, utilizing various polymer feed ratios including polyvinyl alcohol (PVA), polyvinylpyrrolidone K30 (PVP-K30), and polylactide-co-glycolide (PLGA) polymers. The loaded DMNP with QTP underwent a comprehensive characterization process encompassing assessments for compatibility, thickness, insertion potential, morphology, thermal behavior, X-ray diffraction, ex-vivo permeation, skin irritation, and histopathological changes. ResultsFTIR studies confirmed the compatibility of QTP with the microneedle patch composites. The thickness of the drug-loaded DMNP ranged from 0.67 mm to 0.97 mm. These microneedles exhibited an impressive penetration depth of 480 μm, with over 80% of the needles maintaining their original shape after piercing Parafilm-M. SEM analysis of the optimized DMNP-2 revealed the formation of sharp-tipped and uniformly surfaced needles, measuring 570 μm in length. Remarkably, the microneedles did not elicit any signs of irritation upon application of the prepared DMNP. The DMNP-2 showcased an impressive cumulative ex-vivo permeation of QTP, reaching 17.82 µg/cm2/hr. Additionally, histopathological assessment of vital organs in rabbits attested to the safety profile of the formulated microneedle patches. ConclusionsIn conclusion, the developed microneedle patch represents a promising strategy for enhancing the transdermal delivery of QTP. This innovative approach has the potential to increase patient compliance, offering a more efficient and patient-friendly method of administering QTP.

Dissolvable microneedle patch enables local delivery of immunomodulatory microparticles containing bifunctional molecules for periodontal tissue regeneration

Periodontitis is initiated by dysbiosis of the oral microbiome. Pathogenic bacteria elicit ineffective immune responses, which damage surrounding tissues and lead to chronic inflammation. Although current treatments typically aim for microbial eradication, they fail to address the significance of immune cell reactions in disease progression. Here, we searched for small molecules as drug candidates and identified a bifunctional antibiotic, azithromycin (AZM), that not only inhibits bacterial growth but also modulates immune cells to suppress inflammation. We further engineered a dissolvable microneedle patch loaded with biodegradable microparticles for local and painless delivery of AZM to the gingival tissues. Inflammatory cytokines were decreased while anti-inflammatory cytokines and M2 macrophage were increased with AZM treatments in vitro. In vivo delivery of the AZM-loaded microneedle patch demonstrated the same effects on cytokine secretion and the promotion of tissue healing and bone regeneration. In addition, microparticles containing anti-inflammatory interleukin-4 alone or in combination with separately-formulated AZM microparticles, had similar or slightly enhanced therapeutic outcomes respectively. The bimodal action of AZM obviates the necessity for separate antibacterial and immunomodulatory agents, providing a practical and streamlined approach for clinical treatment. Our findings also demonstrate the therapeutic efficacy of microparticles delivery into the soft tissues by a minimally invasive and fast-degrading microneedle patch and offer a novel therapeutic approach for the treatment of periodontitis and other diseases through immunomodulation.Graphical

Micro/nano system-mediated local treatment in conjunction with immune checkpoint inhibitor against advanced-Stage malignant melanoma

Tumor relapse and metastasis become a big challenge in treating malignant melanoma because conventional therapeutic options often fail to eradicate the tumor residue after surgical resection, posing huge threat to human health. Herein, a feasible strategy is developed for fighting crafty melanoma pre- and postsurgery. Specifically, nitric oxide (NO)-carried micelles (NOM) are designed by conjugating S-nitrosoglutathione (GSNO) with poly(2-ethyl-2-oxazoline)-b-poly(D, L-lactide) (PEOz-b-PLA) to form amphipathic polymer, which can self-assemble into pH-sensitive micelle to encapsulate chemotherapeutic drug paclitaxel (PTX). By further loading PTX@NOM into the needle tips of dissolvable microneedle (MN) patch, a local synergistic strategy is achieved for combating melanoma via easy insertion. Meanwhile, due to the immunomodulatory ability of NO by inducing the immunogenic cell death (ICD) of tumor cells and polarizing M2-like tumor-associated macrophages (TAMs) into antitumoral M1-like type, the “cold” immune microenvironment of melanoma is effectively remodeled. When combining with aPD-L1-based immune checkpoint blockade therapy, the treatment outcome of aPD-L1 is dramatically boosted, which not only suppresses primary tumor growth, but also inhibits the notorious post-operative melanoma recurrence and metastasis. Overall, this local strategy mediated by nanoparticle-loaded MN patch expands the therapeutic regimen for melanoma treatment in clinic.

Transdermal delivery of iguratimod and colchicine ethosome by dissolving microneedle patch for the treatment of recurrent gout

This study introduces a novel approach of repetitive modeling to simulate the pathological process of recurrent gout attacks in humans. This methodology addresses the instability issues present in rat models of gout, providing a more accurate representation of the damage recurrent gout episodes inflict on human skeletal systems. A soluble nanoneedle system encapsulating colchicine and iguratimod ethosomal formulations was developed. This system aims to modulate inflammatory cytokines and inhibit osteoclast activity, thereby treating inflammatory pain and bone damage associated with recurrent gout. Additionally, a comprehensive evaluation of the microneedles' appearance, morphology, mechanical properties, and penetration capability confirmed their effectiveness in penetrating the stratum corneum. Dissolution tests and skin irritation assessments demonstrated that these microneedles dissolve rapidly without irritating the skin. In vitro permeation studies indicated that transdermal drug delivery via these microneedles is more efficient and incurs lower drug loss compared to traditional topical applications. In vivo pharmacodynamic assessments conducted in animal models revealed significant analgesic and anti-inflammatory effects when both types of microneedles were used together. Further analyses, including X-ray imaging, hematoxylin and eosin (H&E) staining, Safranin-O/fast green staining, tartrate-resistant acid phosphatase staining, and quantification of osteoclasts, confirmed the bone-protective effects of the microneedle combination. In conclusion, the findings of this research underscore the potential of this novel therapeutic approach for clinical application in the treatment of recurrent gout.

Novel strategy for Poxviridae prevention: Thermostable combined subunit vaccine patch with intense immune response

Poxviruses gained international attention due to the sharp rise in monkeypox cases in recent years, highlighting the urgent need for the development of a secure and reliable vaccine. This study involved the development of an innovative combined subunit vaccine (CSV) targeting poxviruses, with lumpy skin disease virus (LSDV) serving as the model virus. To this end, the potential sites for poxvirus vaccines were fully evaluated to develop and purify four recombinant proteins. These proteins were then successfully delivered to the dermis in a mouse model by utilizing dissolvable microneedle patches (DMPs). This approach simplified the vaccination procedure and significantly mitigated the associated risk. CSV-loaded DMPs contained four recombinant proteins and a novel adjuvant, CpG, which allowed DMPs to elicit the same intensity of humoral and cellular immunity as subcutaneous injection. Following immunization with SC and DMP, the mice exhibited notable levels of neutralizing antibodies, albeit at a low concentration. It is noteworthy that the CSV loaded into DMPs remained stable for at least 4 months at room temperature, effectively addressing the storage and transportation challenges. Based on the study findings, CSV-loaded DMPs are expected to be utilized worldwide as an innovative technique for poxvirus inoculation, especially in underdeveloped regions. This novel strategy is crucial for the development of future poxvirus vaccines.

Systemic delivery of bictegravir and tenofovir alafenamide using dissolving microneedles for HIV preexposure prophylaxis

Human immunodeficiency virus (HIV) continues to pose a serious threat to global health. Oral preexposure prophylaxis (PrEP), considered highly effective for HIV prevention, is the utilisation of antiretroviral (ARV) drugs before HIV exposure in high-risk uninfected individuals. However, ARV drugs are associated with poor patient compliance and pill fatigue due to their daily oral dosing. Therefore, an alternative strategy for drug delivery is required. In this work, two dissolving microneedle patches (MNs) containing either bictegravir (BIC) or tenofovir alafenamide (TAF) solid drug nanoparticles (SDNs) were developed for systemic delivery of a novel ARV regimen for potential HIV prevention. According to ex vivo skin deposition studies, approximately 11% and 50% of BIC and TAF was delivered using dissolving MNs, respectively. Pharmacokinetic studies in Sprague Dawley rats demonstrated that BIC MNs achieved a long-acting release profile, maintaining the relative plasma concentration above the 95% inhibitory concentration (IC95) for 3 weeks. For TAF MNs, a rapid release of drug and metabolism of TAF into TFV were obtained from the plasma samples. This work has shown that the proposed transdermal drug delivery platform could be potentially used as an alternative method to systemically deliver ARV drugs for HIV PrEP.

Analysis of research trends on microneedle patches loaded pharmacopuncture preparation: A Literature Review

Objectives: The purpose of this study is to review the dissolving microneedle patches literature, which is loaded with pharmacopuncture preparation. By exploring types of pharmacopuncture preparation applied to microneedle patches, we aim to develop new potential preparation.Methods: This review included both animal and human studies that published between February 2015 and March 2024. After searching, no RCTs were found, the final selected in-vivo and in-vitro studies were analyzed. A total of 13 articles were retrieved from the international database, and a total of 5 articles were retrieved from the domestic database. Finally, 7 studies were selected, and evaluated by the published year, country of publication, types of animal model, disease type, retention type, evaluation index, adverse effects.Conclusions: According to 7 studies, pharmacopuncture preparation coated dissolving microneedle patch include bee venom, placenta, and ginseng in osteoarthritis, rheumatoid arthritis, hypertrophic scar, psoriasis, and neurodegeneration. In the future, follow-up studies on the safety, retention time, and optimal effective dose of the microneedle patches are expected.

Iontophoresis-coupled rapidly dissolving polymeric microneedle patch of naloxone for its enhanced transdermal delivery

The transdermal delivery of naloxone for opioid overdose emergency purposes is a challenge due to its poor rate of diffusion through the layers of skin. This results in delayed delivery of an insufficient amount of the drug within minimal time as is desired to save lives. The ability of dissolving polymeric microneedles to shorten the lag time significantly has been explored and shown to have prospects in terms of the transdermal delivery of naloxone. This is an option that offers critical advantages to the ongoing opioid crisis, including ease of distribution and easy administration, with little to no need for intervention by clinicians. Nonetheless, this approach by itself needs augmentation to meet pharmacokinetic delivery attributes desired for a viable clinical alternative to existing market dosage forms. In this study, we report the success of an optimized iontophoresis-coupled naloxone loaded dissolving microneedle patch which had facilitated a 12- fold increase in average cumulative permeation and a 6-fold increase in drug flux over a conventional dissolving microneedle patch within 60 min of application (p < 0.05). This translates to a 30 % decrease in dose requirement in a mechanistically predicted microneedle patch established to be able to achieve the desired early plasma concentration time profile needed in an opioid overdose emergency. Applying a predictive mathematical model, we describe an iontophoresis-coupled microneedle patch design capable of meeting the desired pharmacokinetic profile for a viable naloxone delivery form through skin.

Highly efficient prevention of radiation dermatitis using a PEGylated superoxide dismutase dissolving microneedle patch

PEGylated superoxide dismutase (PEG-SOD) is commonly used as a cytoprotective agent in radiotherapy. However, its effectiveness in preventing radiation dermatitis is limited owing to its poor skin permeability. To address this issue, a PEG-SOD-loaded dissolving microneedle (PSMN) patch was developed to effectively prevent radiation dermatitis. Initially, PSMN patches were fabricated using a template mold method with polyvinylpyrrolidone K90 as the matrix material. PSMNs exhibited a conical shape with adequate mechanical strength to penetrate the stratum corneum. More than 90 % of PEG-SOD was released from the PSMN patches within 30 min. Notably, the PSMN patches showed a significantly higher drug skin permeation than the PEG-SOD solutions, with a 500-fold increase. In silico simulations and experiments on skin pharmacokinetics confirmed that PSMN patches enhanced drug permeation and skin absorption, in contrast to PEG-SOD solutions. More importantly, PSMN patches efficiently mitigated ionizing radiation-induced skin damage, accelerated the healing process of radiation-affected skin tissues, and exhibited highly effective radioprotective activity for DNA in the skin tissue. Therefore, PSMN patches are promising topical remedy for the prevention of radiation dermatitis.

Design and development of a soluble PDA-Emodin-PVP-MN patch and its anti-obesity effect in rats.

Emodin has been proven to have weight-reducing and lipid-lowering effects. In order to make emodin play a better anti-obesity role, we designed and developed an emodin loaded dissolving microneedle patch, in which emodin existed in the form of emodin-polyvinylpyrrolidone co-precipitate (Emodin-PVP). Meanwhile, polydopamine (PDA) was added to the microneedle patch (PDA-Emodin-PVP-MN) for photothermal-enhanced chemotherapy of obesity. The average weight of the patch was 0.1 ± 0.05g and the drug loading was 0.37 ± 0.031mg. After 5min of NIR irradiation (808nm, 0.6 W/cm2), the rat abdominal temperature could reach 48 ℃, and the cumulative release of emodin reached 96.25%. The diffusion coefficient of emodin in the in vitro agar diffusion experiment was 249.27 mm2h-1. No obvious toxicity was observed in hemolysis test, CCK-8 assay and microscopic histopathological analysis. The patch significantly reduced the percent of body weight ( P < 0.01), lipid-body ratio ( P < 0.001), serum FFAs ( P < 0.01) and the cell volume of peritesticular adipose tissue in the high-fat diet induced obese rats, indicating the patch had good anti-obesity effect. The mechanism of action may be related to the up-regulation of HSL and LPL protein levels in rat peritesticular adipose tissue.

Calcipotriol Nanosuspension-Loaded Trilayer Dissolving Microneedle Patches for the Treatment of Psoriasis: In Vitro Delivery and In Vivo Antipsoriatic Activity Studies.

Psoriasis, affecting 2-3% of the global population, is a chronic inflammatory skin condition without a definitive cure. Current treatments focus on managing symptoms. Recognizing the need for innovative drug delivery methods to enhance patient adherence, this study explores a new approach using calcipotriol monohydrate (CPM), a primary topical treatment for psoriasis. Despite its effectiveness, CPM's therapeutic potential is often limited by factors like the greasiness of topical applications, poor skin permeability, low skin retention, and lack of controlled delivery. To overcome these challenges, the study introduces CPM in the form of nanosuspensions (NSs), characterized by an average particle size of 211 ± 2 nm. These CPM NSs are then incorporated into a trilayer dissolving microneedle patch (MAP) made from poly(vinylpyrrolidone) and w poly(vinyl alcohol) as needle arrays and prefrom 3D printed polylactic acid backing layer. This MAP features rapidly dissolving tips and exhibits good mechanical properties and insertion capability with delivery efficiency compared to the conventional Daivonex ointment. The effectiveness of this novel MAP was tested on Sprague-Dawley rats with imiquimod-induced psoriasis, demonstrating efficacy comparable to the marketed ointment. This innovative trilayer dissolving MAP represents a promising new local delivery system for calcipotriol, potentially revolutionizing psoriasis treatment by enhancing drug delivery and patient compliance.

Hyaluronic acid dissolving microneedle patch loaded with tranexamic acid for melasma treatment

Melasma is an acquired hypermelanotic condition characterized by the presence of irregular light-to-dark brown macules that primarily manifest on the sun-exposed areas of the skin, particularly the face. The management of melasma poses significant challenges, as it is often recalcitrant to treatment and tends to recur despite successful treatment. In this study, we explored a safe, easy, and effective melasma treatment strategy. A hyaluronic acid (HA)-based microneedle (MN) patch loaded with tranexamic acid (TXA) was designed to deliver the necessary medication for melasma treatment. The MN patch features uniform needles with adequate mechanical strength and effective penetration and solubility in the skin without cytotoxicity. Remarkably, these MNs substantially reduce the thickness of the epidermis of melasma mice, curtail melanin production, and diminish dopachrome tautomerase (DCT) expression.