Microneedle Patch Research Articles

Microneedle delivery system with rapid dissolution and sustained release of bleomycin for the treatment of hemangiomas

Hemangioma of infancy is the most common vascular tumor during infancy and childhood. Despite the proven efficacy of propranolol treatment, certain patients still encounter resistance or face recurrence. The need for frequent daily medication also poses challenges to patient adherence. Bleomycin (BLM) has demonstrated effectiveness against vascular anomalies, yet its use is limited by dose-related complications. Addressing this, this study proposes a novel approach for treating hemangiomas using BLM-loaded hyaluronic acid (HA)-based microneedle (MN) patches. BLM is encapsulated during the synthesis of polylactic acid (PLA) microspheres (MPs). The successful preparation of PLA MPs and MN patches is confirmed through scanning electron microscopy (SEM) images. The HA microneedles dissolve rapidly upon skin insertion, releasing BLM@PLA MPs. These MPs gradually degrade within 28 days, providing a sustained release of BLM. Comprehensive safety assessments, including cell viability, hemolysis ratio, and intradermal reactions in rabbits, validate the safety of MN patches. The BLM@PLA-MNs exhibit an effective inhibitory efficiency against hemangioma formation in a murine hemangioma model. Of significant importance, RNA-seq analysis reveals that BLM@PLA-MNs exert their inhibitory effect on hemangiomas by regulating the P53 pathway. In summary, BLM@PLA-MNs emerge as a promising clinical candidate for the effective treatment of hemangiomas.Graphical

Poly(2-Hydroxyethyl Methacrylate) Hydrogel-Based Microneedles for Bioactive Release.

Microneedle arrays are minimally invasive devices that have been extensively investigated for the transdermal/intradermal delivery of drugs/bioactives. Here, we demonstrate the release of bioactive molecules (estradiol, melatonin and meropenem) from poly(2-hydroxyethyl methacrylate), pHEMA, hydrogel-based microneedle patches in vitro. The pHEMA hydrogel microneedles had mechanical properties that were sufficiently robust to penetrate soft tissues (exemplified here by phantom tissues). The bioactive release from the pHEMA hydrogel-based microneedles was fitted to various models (e.g., zero order, first order, second order). Such pHEMA microneedles have potential application in the transdermal delivery of bioactives (exemplified here by estradiol, melatonin and meropenem) for the treatment of various conditions.

Multifunctional Microneedle Patch Based on Metal-Phenolic Network with Photothermal Antimicrobial, ROS Scavenging, Immunomodulatory, and Angiogenesis for Programmed Treatment of Diabetic Wound Healing.

In diabetic patients with skin injuries, bacterial proliferation, accumulation of reactive oxygen species (ROS) in the tissues, and impaired angiogenesis make wound healing difficult. Therefore, eliminating bacteria, removing ROS, and promoting angiogenesis are necessary for treating acute diabetic wounds. In this study, benefiting from the ability of polyphenols to form a metal-phenolic network (MPN) with metal ions, TA-Eu MPN nanoparticles (TM NPs) were synthesized. The prepared photothermal agent CuS NPs and TM NPs were then loaded onto the supporting base and needle tips of PVA/HA (PH) microneedles, respectively, to obtain PH/CuS/TM microneedles. Antibacterial experiments showed that microneedles loaded with CuS NPs could remove bacteria by the photothermal effect. In vitro experiments showed that the microneedles could effectively scavenge ROS, inhibit macrophage polarization to the M1 type, and induce polarization to the M2 type as well as have the ability to promote vascular endothelial cell migration and angiogenesis. Furthermore, in vivo experiments showed that PH/CuS/TM microneedles accelerated wound healing by inhibiting pro-inflammatory cytokines and promoting angiogenesis in a diabetic rat wound model. Therefore, PH/CuS/TM microneedles have efficient antibacterial, ROS scavenging, anti-inflammatory, immunomodulatory, and angiogenic abilities and hold promise as wound dressings for treating acute diabetic wounds.

Curcumin analogue AC17-loaded dissolvable microneedles activate FOXO3 and enhance localized drug delivery for oral squamous cell carcinoma treatment

Curcumin, a polyphenol extracted from turmeric, is a potential alternative for the treatment of oral squamous cell carcinoma (OSCC) due to its remarkable anticancer activity and low systemic toxicity. To further enhance the anticancer activity and bioavailability of curcumin, we synthesized a curcumin analogue, AC17, by modifying the benzene ring and methylene group of curcumin. A soluble hyaluronic acid microneedle patch (AC17@HAMN) was developed to ensure accurate and safe delivery of AC17 to tumor tissues. The inhibitory effect of AC17 on OSCC cells was stronger than that of curcumin and some common analogues. Transcriptome sequencing showed that the target genes of AC17 were mainly concentrated in apoptosis, cell cycle and cell senescence pathways. Among them, AC17 induces cell cycle arrest and inhibits cell proliferation mainly by activating FOXO3 signaling. With good penetration and dissolution properties, microneedles can deliver AC17 directly to the tumor site and show good anti-tumor effect. Moreover, AC17@HAMN showed good biosafety. In summary, AC17@HAMN offers high efficiency, minimal invasiveness, and few adverse reactions. This microneedle patch holds great promise for potential clinical applications, especially for the treatment of OSCC.

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.

Multifunctional composite soluble microneedle patch based on “one stone, three birds” strategy for promoting the healing of infectious wounds

The colonisation of microorganisms such as bacteria forms a biofilm barrier on the wound's surface, preventing or delaying the penetration of antibacterial drugs. At the same time, continuous bacterial infection can cause oxidative stress and an inflammatory response and hinder angiogenesis, resulting in difficult wound healing. Based on the “one stone, three birds” strategy, a multi-functional nanoparticle composite soluble microneedle was designed and developed to solve this dilemma better. Ginsenoside-liposomes(R-Lipo) were prepared by ginsenoside Rg3, which had the effect of promoting repair, instead of cholesterol, and loaded with berberine (Ber), the antibacterial component of Coptis, together with polydopamine (PDA), which had anti-inflammatory and antioxidant properties, into microneedles based on hyaluronic acid (PDA/R-Lipo@BerMN). PDA/R-Lipo@BerMN tip can penetrate and destroy the integrity of the biofilm, dissolve under the action of hyaluronidase in the skin, and gradually release the drug to achieve rapid antibacterial, anti-inflammatory, antioxidant, and proliferation. As expected, the PDA/R-Lipo@BerMN patch effectively cleared ROS during wound closure, further promoted M2 macrophage polarisation, eradicated bacterial infection, and regulated the immune microenvironment, promoting inflammation suppression, collagen deposition, angiogenesis, and tissue regeneration.

A Split-Face Comparison of Novel Microneedle Patch versus Botulinum Toxin-A and Microneedle Patch for Improvement in Undereye Skin Texture

(1) Background: The emergence of microneedle patch technology and its development as a transdermal drug delivery platform have shown proven results in improving skin texture and appearance. This study was conducted to determine the efficacy of the microneedle patch (MNP)-only cosmesis of undereye skin texture and wrinkles against patch cosmesis with diluted botulinum toxin-A. (2) Methods: A total of 23 Thai females volunteered for this prospective clinical trial. Each participant was treated according to a split-face design, with the application of diluted botulinum toxin-A through MNP technology to the right undereye and a normal saline MNP application to the left undereye. Test areas were recorded at baseline and 2, 4, 8, 12, and 16 weeks after the initial treatment. (3) Results: Botulinum toxin-A was successfully delivered to the skin by MNP technology. After the initial treatment, these novel transdermal drug delivery patches significantly improved infraorbital hollowness at week 8 and wrinkles at week 16. In addition, the skin surface was markedly enhanced, with no adverse effects observed during the trial. (4) Conclusions: Novel MNPs are an effective and safe technology for use in the management of undereye skin aging. Combination treatment with botulinum toxin-A-impregnated devices gave a higher patient satisfaction than MNPs alone.

(3D) Bioprinting-Next Dimension of the Pharmaceutical Sector.

To create a review of the published scientific literature on the benefits and potential perspectives of the use of 3D bio-nitrification in the field of pharmaceutics. This work was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for reporting meta-analyses and systematic reviews. The scientific databases PubMed, Scopus, Google Scholar, and ScienceDirect were used to search and extract data using the following keywords: 3D bioprinting, drug research and development, personalized medicine, pharmaceutical companies, clinical trials, drug testing. The data points to several aspects of the application of bioprinting in pharmaceutics were reviewed. The main applications of bioprinting are in the development of new drug molecules as well as in the preparation of personalized drugs, but the greatest benefits are in terms of drug screening and testing. Growth in the field of 3D printing has facilitated pharmaceutical applications, enabling the development of personalized drug screening and drug delivery systems for individual patients. Bioprinting presents the opportunity to print drugs on demand according to the individual needs of the patient, making the shape, structure, and dosage suitable for each of the patient's physical conditions, i.e., print specific drugs for controlled release rates; print porous tablets to reduce swallowing difficulties; make transdermal microneedle patches to reduce patient pain; and so on. On the other hand, bioprinting can precisely control the distribution of cells and biomaterials to build organoids, or an Organ-on-a-Chip, for the testing of drugs on printed organs mimicking specified disease characteristics instead of animal testing and clinical trials. The development of bioprinting has the potential to offer customized drug screening platforms and drug delivery systems meeting a range of individualized needs, as well as prospects at different stages of drug development and patient therapy. The role of bioprinting in preclinical and clinical testing of drugs is also of significant importance in terms of shortening the time to launch a medicinal product on the market.

Anti-inflammatory PEGylated bilirubin microneedle patch for diabetes treatment

The long-term hyperglycemic environment could easily cause chronic metabolic inflammation with physiological disorders, exacerbate inflammatory cytokine storms, increase the risk of patients contracting other complications. Thus, to develop glucose-responsive insulin delivery microneedles with anti-inflammatory is of much importance. Herein, a novel in-situ H2O2-sensitive insulin delivery microneedle array patch was constructed for the intelligent management of blood glucose in diabetics, which was integrated with nanoparticles (NPs) to achieve synergistic enhancement of anti-inflammatory and antioxidant functions. Specifically, PEGylated bilirubin (BR) nanoparticles were loaded with insulin and glucose-sensing element glucose oxidase (GOD), named as I@PEG-BR/GOD NPs, which could release drugs in response to high concentrations of glucose. Moreover, bilirubin with potent antioxidant and anti-inflammatory functions could induce reprogramming macrophages to M2 type polarization, which was much beneficial to inhibit inflammation caused by hyperglycemia. In vivo results demonstrated such in situ H2O2-sensitive insulin delivery microneedle array patch had good anti-inflammatory and antioxidant therapeutic efficacy in a mice model of diabetes. This novel glucose-responsive insulin delivery combined with the anti-inflammatory functions of microneedle patches show great promising for the treatment of diabetes with safe controlled release of insulin.

Dissolving microarray patches for transdermal delivery of risperidone for schizophrenia management

Schizophrenia is a psychiatric disorder that results from abnormal levels of neurotransmitters in the brain. Risperidone (RIS) is a common drug prescribed for the treatment of schizophrenia. RIS is a hydrophobic drug that is typically administered orally or intramuscularly. Transdermal drug delivery (TDD) could potentially improve the delivery of RIS. This study focused on the development of RIS nanocrystals (NCs), for the first time, which were incorporated into dissolving microneedle array patches (DMAPs) to facilitate the drug delivery of RIS. RIS NCs were formulated via wet-media milling technique using poly(vinylalcohol) (PVA) as a stabiliser. NCs with particle size of 300 nm were produced and showed an enhanced release profile up to 80 % over 28 days. Ex vivo results showed that 1.16 ± 0.04 mg of RIS was delivered to both the receiver compartment and full-thickness skin from NCs loaded DMAPs compared to 0.75 ± 0.07 mg from bulk RIS DMAPs. In an in vivo study conducted using female Sprague Dawley rats, both RIS and its active metabolite 9-hydroxyrisperidone (9-OH-RIS) were detected in plasma samples for 5 days. In comparison with the oral group, DMAPs improved the overall pharmacokinetic profile in plasma with a ∼ 15 folds higher area under the curve (AUC) value. This work has represented the novel delivery of the antipsychotic drug, RIS, through microneedles. It also offers substantial evidence to support the broader application of MAPs for the transdermal delivery of poorly water-soluble drugs.

Degradable Microneedle Patch with Photothermal-Promoted Bacteria-Infected Wound Healing and Microenvironment Remodeling.

Bacteria-infected wound healing is one of the most challenging issues in health management that is attracting worldwide concerns. Despite great achievements with antibiotics, emergence of antibiotic-resistance retarded the wound healing process and also led to severe outcomes. Exploration of novel antibiotics together with amelioration of wound healing efficacy is desirable. Herein, a degradable microneedle patch (AAZH@MNs) was fabricated through incorporating near-infrared light responsive photothermal agents for sustained bacteria killing and prevention of biofilm formation. In addition, the antibacterial microneedle patch could even remold the microenvironment of bacteria-infected wounds through an antibacterial effect, significantly facilitating the wound healing process.

Emerging Technologies in Endocrine Drug Delivery: Innovations for Improved Patient Care.

Recent advancements in drug delivery systems for endocrine disorders have significantly improved patient outcomes by addressing the limitations of traditional methods such as oral tablets and injections. These innovations include non-invasive alternatives like inhaled insulin, which provides rapid absorption and better patient compliance, and robotic pills that deliver drugs directly to specific gastrointestinal sites, enhancing absorption and reducing side effects. Wearable artificial pancreas systems have revolutionized diabetes management by integrating continuous glucose monitoring with insulin pumps to automate blood glucose control. These systems demonstrate superior glycemic control and reduce hypoglycemic events. Additionally, smart insulin pens enhance diabetes care through dose tracking and real-time data sharing, improving accuracy and adherence. Microneedle patches offer a minimally invasive method for transdermal drug delivery, effectively administering hormones and therapeutic peptides without the pain and inconvenience of injections. These patches dissolve after use, eliminating biohazardous waste. Implantable devices provide long-term, controlled release of medications, significantly improving adherence and glycemic control of patients with diabetes. Hydrogels also offer new drug delivery options. This review examines these technologies' clinical efficacy, safety, advantages, and limitations, highlighting their potential to transform endocrine disorder management. Integrating advanced delivery systems marks a significant step towards personalized medicine, tailoring treatments to individual patient needs for better health outcomes.

Grooved Microneedle Patch Augments Adoptive T Cell Therapy Against Solid Tumors via Diverting Regulatory T Cells.

The efficacy of adoptive T cell therapy (ACT) for the treatment of solid tumors remains challenging. In addition to the poor infiltration of effector T (Teff) cells limited by the physical barrier surrounding the solid tumor, another major obstacle is the extensive infiltration of regulatory T (Treg) cells, a major immunosuppressive immune cell subset, in the tumor microenvironment. Here, this work develops a grooved microneedle patch for augmenting ACT, aiming to simultaneously overcome physical and immunosuppressive barriers. The microneedles are engineered through an ice-templated method to generate the grooved structure for sufficient T-cell loading. In addition, with the surface modification of chemokine CCL22, the MNs could not only directly deliver tumor-specific T cells into solid tumors through physical penetration, but also specifically divert Treg cells from the tumor microenvironment to the surface of the microneedles via a cytokine concentration gradient, leading to an increase in the ratio of Teff cells/Treg cells in a mouse melanoma model. Consequently, this local delivery strategy of both T cell receptor T cells and chimeric antigen receptor T cells via the CCL22-modified grooved microneedles as a local niche could significantly enhance the antitumor efficacy and reduce the on-target off-tumor toxicity of ACT.

Transdermal microneedle patches as a promising drug delivery system for anti-obesogenic molecules.

Obesity, characterized by excessive storage of lipids, has become a global pandemic with high incidence levels, and its forecast is not encouraging. Currently, there are different strategies to treat obesity; however, these conventional methods have various limitations. Lifestyle changes may result in poor outcomes due to the complexity of obesity causes, pharmaceutic treatments produce severe side effects, and bariatric surgery is highly invasive. In the search for alternative treatments to fight obesity, transdermal drug delivery systems of anti-obesogenic molecules have gained particular attention. However, the diffusion of molecules through the skin is the main drawback due to the characteristics of different layers of the skin, principally the stratum corneum and its barrier-like behavior. In this sense, microneedles patches (MP) have emerged to overcome this limitation by piercing the skin and allowing drug delivery inside the body. Although MP have been studied for some years, it was not until about 2017 that their potential as anti-obesogenic treatment was reported. This article aims to summarize and analyze the strategies employed to produce MP and to embed the active molecules against obesity. Special attention is focused on the microneedle's material, geometry, array, and additional delivery strategies, like nanoencapsulation. MP are a promising tool to develop an easy-access treatment, avoiding the digestive tract and with the capacity to enhance the anti-obesogenic activity by delivering one or more active molecules.

A Co-MOF encapsulated microneedle patch activates hypoxia induction factor-1 to pre-protect transplanted flaps from distal ischemic necrosis

Avoiding ischemic necrosis after flap transplantation remains a significant clinical challenge. Developing an effective pretreatment method to promote flap survival postoperatively is crucial. Cobalt chloride (CoCl2) can increase cell tolerance to ischemia and hypoxia condition by stimulating hypoxia-inducible factor-1 (HIF-1) expression. However, the considerable toxic effects severely limit the clinical application of CoCl2. In this study, cobalt-based metal-organic frameworks (Co-MOF) encapsulated in a microneedle patch (Co-MOF@MN) was developed to facilitate the transdermal sustained release of Co2+ for rapid, minimally invasive rapid pretreatment of flap transplantation. The MN patch was composed of a fully methanol-based two-component cross-linked polymer formula, with a pyramid structure and high mechanical strength, which satisfied the purpose of penetrating the skin stratum corneum of rat back to achieve subcutaneous vascular area administration. Benefiting from the water-triggered disintegration of Co-MOF and the transdermal delivery via the MN patch, preoperative damage and side effects were effectively mitigated. Moreover, in both the oxygen-glucose deprivation/recovery (OGD/R) cell model and the rat dorsal perforator flap model, Co-MOF@MN activated the HIF-1α pathway and its associated downstream proteins, which reduced reperfusion oxidative damage, improved blood supply in choke areas, and increased flap survival rates post-transplantation. This preprotection strategy, combining MOF nanoparticles and the MN patch, meets the clinical demands for trauma minimization and uniform administration in flap transplantation. Statement of significanceCobalt chloride (CoCl2) can stimulate the expression of hypoxia-inducible factor (HIF-1) and improve the tolerance of cells to ischemia and hypoxia conditions. However, the toxicity and narrow therapeutic window of CoCl2 severely limit its clinical application. Herein, we explored the role of Co-MOF as a biocompatible nanocage for sustained release of Co2+, showing the protective effect on vascular endothelial cells in the stress model of oxygen-glucose deprivation. To fit the clinical needs of minimal trauma in flap transplantation, a Co-MOF@MN system was developed to achieve local transdermal delivery at the choke area, significantly improving blood supply opening and flap survival rate. This strategy of two-step delivery of Co2+ realized the enhancement of biological functions while ensuring the biosafety.

Converging paths: Microneedle-based dual intervention of IL-23/IL-17 axis and granuloma formation in rheumatoid nodules

Rheumatoid nodules (RNs) are an extra-articular manifestation of rheumatoid arthritis and are frequently observed in patients with autoimmune and inflammatory conditions. The development of RNs involves several stages, including inflammation of blood vessels, cell death triggered by medications, and infiltration of inflammatory cells leading to nodule formation. Recent studies highlight the importance of the IL-23/IL-17 axis and the migration of chronic inflammatory cells in this process, forming palisading granulomas. Current treatments often fail to manage RNs effectively because they tend to reoccur and appear in multiple locations. This study proposes a new therapeutic strategy combining corticosteroid treatment with gene silencing therapy using small interfering RNA (siRNA) targeting IL-23. Targeting these inflammatory pathways simultaneously aims to reduce both the size and number of nodules, potentially shortening the treatment duration. An innovative delivery system utilizing lipid-polymer hybrid nanoparticles (LPNs) and hyaluronic acid-based dissolving microneedles (MNs) is proposed to be developed. The LPNs will be designed with DOTAP (1,2-dioleoyl-3-trimethylammonium propane) and DSPE-PEG (distearoyl-phosphoethanolamine-polyethylene glycol) as the lipid core, along with poly-lactic-co-glycolic acid (PLGA) polymer. These MN patches would improve the skin’s permeability, allowing LPN carrying the siRNA and corticosteroid to penetrate effectively. This non-invasive approach is expected to enhance the diffusion of LPNs into the skin, thereby increasing the availability of the therapeutic payload. Therefore, we hypothesize that targeting the IL-23/IL-17 axis and granuloma formation with the synergistic combination of targeted therapy and advanced delivery technology will revolutionize the treatment of RNs.

Fiber-Reinforced Silk Microneedle Patches for Improved Tissue Adhesion in Treating Diabetic Wound Infections

Fiber-Reinforced Silk Microneedle Patches for Improved Tissue Adhesion in Treating Diabetic Wound Infections

A novel and sensitive microneedle array platform for visual detection of glucose based on Zr-MOF@Pt nanozyme with peroxidase-like activity

The level of glucose, one of the body’s energy-providing substances, is closely related to many diseases. Therefore, it remains a challenge to develop platform that can satisfy both the need for accurate detection of glucose for clinical diagnosis as well as device-free and efficient on-site monitoring of blood glucose. Herein, we synthesized Zr-MOFs@Pt nanocomposites for the first time. The peroxidase-like activity of Zr-MOFs@Pt was greatly enhanced two times compared with Zr-MOFs, due to the synergistic effect of Pt nanoparticles that was in situ growing in Zr-MOFs. Hydrogen peroxide was generated from glucose with the catalysis of glucose oxidase (GOx). H2O2 was decomposed by Zr-MOFs@Pt to produce free radical, which could oxidize 3,3′,5,5′-tetramethylbenzidine (TMB) to generate blue oxTMB, and could be utilized for colorimetric sensing of glucose. By crosslinking, TMB and PVA hydrogel matrix formed the microneedle patch display layer, and PVA as well as GOx composed the tip of the needle, the sensing system was developed to hydrogel microneedles array for detection of glucose. When the tip of the needle was inserted into a solution containing glucose, it reacted with GOx in the tip sector to produce H2O2. The H2O2 would react with Zr-MOFs@Pt in the display layer to produce free radicals, and further oxidize TMB causing the display layer to exhibit blue color. This work provides a new approach for designing device-free sensing platforms for glucose monitoring, which also offers great potential for development of microneedle analytical devices.

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.

The Comparative Efficacy and Safety of 250 μm versus 350 μm Long Microneedle Patch on Under-Eye Skin

Background: Microneedle patch (MNP) technology is now applied for many purposes, including transdermal drug delivery and percutaneous collagen induction in the cosmetic and dermatology fields. Previous research showed that a MNP effectively improved skin appearance, while treatments using larger or deeper microneedles were not easily tolerated by human subjects. Few studies have compared MNP designs in humans. Study Objective: To compare novel MNP designs with high length and low density versus low length and high density for rejuvenating skin wrinkles under the eyes. Methods: This non-randomized split-face clinical trial was conducted as a double-blind study with 36 Thai female participants. Each participant was treated with two different MNP designs, one on each side of the face. The microneedle lengths were 250 μm with a density of 945 needles/cm2 on the left side of the face under the eye and 350 μm with a density of 482 needles/cm2 on the right side of the face under the eye. The treatments were applied for 12 weeks, with the assessment outcomes evaluated at the baseline and 2, 4, 6, 8, 10, and 12 weeks. Results: The application of these two novel MNP designs successfully rejuvenated under-eye wrinkles with low pain level scores. Increasing the length of the needle or having a 350 μm long MN can better reduce under-eye wrinkles without statistical significance. During the study period, there was an improvement in skin surface roughness in both groups accompanied by a consistent reduction in under-eye skin wrinkles, without statistically significant differences observed between the groups when using the Antera 3D system. However, the 350 μm long MN also slightly increased the pain compared to the shorter needles (250 μm long MN) with a higher density of needles. There were no side effects associated with the two designs. Conclusions: The two novel MNPs gave favorable results as a safe non-invasive treatment for the rejuvenation of skin wrinkles under the eyes. Increasing the number of needles and increasing the length of the needles were both effective in safely reducing under-eye wrinkles without any adverse effects. Additionally, participants could self-apply them at home and were highly satisfied. However, increasing the length of the needles may result in slightly more pain compared to increasing the number of needles.