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The integrated smart electronics for real-time monitoring and personalized therapy of disease-related analytes have been gradually gaining tremendous attention. However, human tissue barriers, including the skin barrier and brain-blood barrier, pose significant challenges for effective biomarker detection and drug delivery. Microneedle (MN) electronics present a promising solution to overcome these tissue barriers due to their semi-invasive structures, enabling effective drug delivery and target-analyte detection without compromising the tissue configuration. Furthermore, MNs can be fabricated through solution processing, facilitating large-scale manufacturing. This review provides a comprehensive summary of the recent three-year advancements in smart MNs development, categorized as follows. First, the solution-processed technology for MNs is introduced, with a focus on various printing technologies. Subsequently, smart MNs designed for sensing, drug delivery, and integrated systems combining diagnosis and treatment are separately summarized. Finally, the prospective and promising applications of next-generation MNs within mediated diagnosis and treatment systems are discussed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The development of an effective transdermal drug delivery protocol to eccrine sweat glands is important for the advancement of research on the human sweating response. We investigated whether microneedle treatment prior to the application of pilocarpine, a hydrophilic and sudorific agent that does not induce sweating due to a limited percutaneous passive diffusion by skin application alone, augments sweat production. We applied three microneedle arrays to forearm skin sites simultaneously (n = 20). Upon removal of the microneedles, 1 % pilocarpine was applied to each site for 5-, 15-, and 30-min for the assessment of sweat gland function. In parallel, pilocarpine was administered by transdermal iontophoresis (5-min) at a separate site. Sweat rate was assessed continuously via the ventilated capsule technique. Pilocarpine augmented sweat rate at the 15- and 30-min periods as compared to the application at 5-min. The sweating responses induced by the 15- and 30-min application of pilocarpine were equivalent to ∼ 80 % of that measured at the iontophoretically treated sites. Notably, we observed a correlation in sweat rate between these two transdermal drug delivery methods. Altogether, our findings show that pre-treatment of microneedle arrays can enhance transdermal delivery efficiency of pilocarpine to human eccrine sweat glands., Competing Interests: Declaration of competing interest Ying-Shu Quan and Hirofumi Yamashita are employees of CosMED Pharmaceutical Co. Ltd. The views expressed in this manuscript do not represent those of the company. Microneedles array was supplied by CosMED Pharmaceutical Co. Ltd. without any financial support. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: Striae distensae (SD), or stretch marks, result from rapid stretching of the skin due to various factors. Conventional treatments often yield unsatisfactory results, leading to the exploration of alternative methods. Laser-induced microjet technology offers a promising approach for drug delivery to target areas. This study investigates the efficacy of using a microjet injector with poly-d,l-lactic acid for treating SD., Methods: Four female participants with SD were treated with poly-d,l-lactic acid solution using a microjet injector over five sessions. Patients were assessed based on severity scales before and after treatment. Topical anesthetics were applied to minimize discomfort. Injection techniques were optimized to reduce side effects such as bleeding and pain., Results: All patients showed significant improvement in SD appearance after 5-7 treatments. Assessment scales indicated positive outcomes both immediately after treatment and at the 32-week follow-up. Minimal side effects, primarily petechiae, were observed., Discussion: Laser-induced microjet technology offers several advantages, including rapid drug delivery and mechanotransduction effects, promoting skin regeneration. Poly-d,l-lactic acid injections demonstrated effectiveness in treating SD, particularly when delivered via microjet injectors. Patients expressed high satisfaction due to the procedure's minimal invasiveness and quick recovery., Conclusion: Utilizing a needleless microjet injector with poly-d,l-lactic acid shows promise as a treatment for SD, typically requiring 5-7 sessions for optimal results. Mild petechiae may occur as a common side effect. This approach offers an effective and minimally invasive alternative for addressing this common cosmetic concern., (© 2024 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Here, a novel porous microneedle (PMN) device with bilaterally aligned electroosmotic flow (EOF) enabling controllable dual-mode delivery of molecules is developed. The PMNs placed at anode and cathode compartments are modified with anionic poly-2-acrylamido-2-methyl-1-propanesulfonic acid and cationic poly-(3-acrylamidopropyl) trimethylammonium, respectively. The direction of EOF generated by PMN at the cathode compartment is, therefore, reversed from cathode to anode, countering the unwanted cathodal suctioning of interstitial fluid caused by reverse iontophoresis. With the bilateral alignment of EOF, the versatility of the proposed device is evaluated by delivering molecules with different charges and sizes using Franz cell. In addition, a 3D printed probe device is developed to ease practical handling and minimize electrical stimulation by integrating two PMNs in closed proximity. Finally, the performance of the integrated probe device is demonstrated by dual delivery of a variety of molecules (methylene blue, rhodamine B, and fluorescein isothiocyanate-dextran) using pig skin and vaccination using mice with delivered ovalbumin., (© 2024 The Authors. Advanced Healthcare Materials published by Wiley‐VCH GmbH.)

Background: Microneedling is used to enhance transcutaneous drug delivery. However, the extent to which microneedling devices impact filler delivery and whether this varies by filler type, microneedling device type, and treatment sequence is not known., Objective: To histologically assess and quantify the delivery of commonly used fillers through microneedling, using both a microneedling pen and a microneedling roller. In addition, the authors investigated whether there is a variation in filler delivery based on the sequence of microneedling in relation to topical filler application., Methods: Ex vivo human abdominal skin samples were subjected to microneedling pen or microneedling roller treatment. Black tissue marking ink, hyaluronic acid, poly- l -lactic acid, or undiluted calcium hydroxyapatite was topically applied before or immediately after microneedling treatment., Results: Histological evaluation revealed a notable presence of black ink within channels formed by both microneedling treatments (15.5%-98.1%), whereas there was limited presence of the various filler types tested (0%-6.6%) in all settings. Topical application before microneedling treatment led to relatively higher filler/ink deposition within the channels formed by the microneedling treatments compared with topical application after microneedling., Conclusion: Transcutaneous delivery of fillers was not significantly helped by microneedling treatment, whereas the microneedling devices demonstrated effective delivery of an aqueous solution., (Copyright © 2024 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.)

The detachable dissolving microneedles (DDMNs) feature an array of needles capable of being separated from the base sheet during administration. Here they were fabricated to address delivery efficiency and storage stability of insulin. The constructed insulin-DDMN is multi-layered, with 1) a hard tip cover layer; 2) a layer of regular short-acting insulin (RI) mixed with hyaluronic acid (HA) and sorbitol (Sor) which occupies the taper tip region of the needles; 3) a barrier layer situated above the RI layer; and 4) a fast-dissolving layer connecting the barrier layer to the base sheet. RI entrapped in DDMNs exhibited enhanced thermal stability; it could be stored at 40 °C for 35 days without losing significant biological activity. Differential scanning calorimetric analysis revealed that the HA-Sor matrix could improve the denaturation temperature of the RI from lower than room temperature to 186 °C. Tests in ex vivo porcine skin demonstrated RI delivery efficiency of 91±1.59 %. Experiments with diabetic rats revealed sustained release of RI, i.e., when compared to subcutaneous injection with the same RI dose, RI-DDMNs produced slower absorption of insulin into blood circulation, delayed onset of hypoglycemic effect, longer serum insulin half-life, and longer hypoglycemic duration., Competing Interests: Declaration of Competing Interest This work was funded by Center of Excellence in Materials and Bio-Interfaces at Chulalongkorn University and Mineed Technology Company. T.P. was financially supported by the Second Century Fund (C2F) from Chulalongkorn University. Mineed Technology Company owns the detachable microneedle patent., (Copyright © 2024 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Hydrogel-forming microneedle array patches (HFMAPs) are microneedles that create microconduits upon insertion and swelling in the skin, potentially allowing prolonged drug delivery without generating sharps waste. Delivering hydrophobic drugs using HFMAPs poses challenges, which can be addressed using solubility enhancers such as cyclodextrins (CDs). This study aimed to deliver risperidone (RIS) transdermally using HFMAPs. To enhance the aqueous solubility of RIS hydroxypropyl-beta-cyclodextrin (HP-β-CD) and hydroxypropyl-gamma-cyclodextrin (HP-γ-CD) were utilised and their performance was tested using phase solubility studies. The aqueous solubility of RIS was enhanced by 4.75-fold and 2-fold using HP-β-CD and HP-γ-CD, respectively. RIS-HP-β-CD complex (CX) and physical mixture (PM) directly compressed tablets were prepared and combined with HFMAPs. Among the tested formulations, RIS-HP-β-CD PM reservoirs with 11 x 11 PVA/PVP HFMAPs exhibited the best performance in ex vivo studies and were further evaluated in in vivo experiments using female Sprague Dawley rats. The extended wear time of the MAPs resulted in the sustained release of RIS and its active metabolite 9-hydroxyrisperidone (9-OH-RIS) in plasma samples, lasting from 3 to 5 days with a 1-day application and up to 10 days with a 5-day application. For a 1-day application, HFMAPs showed greater systemic exposure to RIS compared to intramuscular control (AUC 0-t : 13330.05 ± 2759.95 ng/mL/hour versus 2706 ± 1472 ng/mL/hour). Moreover, RIS exposure was extended to 5 days (AUC 0-t : 12292.37 ± 1801.94 ng/mL/hour). In conclusion, HFMAPs could serve as an alternative for delivering RIS in a sustained manner, potentially improving the treatment of schizophrenia., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor. Standard therapy includes maximal surgical resection, radiotherapy, and adjuvant temozolomide (TMZ) administration. However, the rapid development of TMZ resistance and the impermeability of the blood-brain barrier (BBB) significantly hinder the therapeutic efficacy. Herein, we developed spatiotemporally controlled microneedle patches (BMNs) loaded with TMZ and niclosamide (NIC) to overcome GBM resistance. We found that hyaluronic acid (HA) increased the viscosity of bovine serum albumin (BSA) and evidenced that concentrations of BSA/HA exert an impact degradation rates exposure to high-temperature treatment, showing that the higher BSA/HA concentrations result in slower drug release. To optimize drug release rates and ensure synergistic antitumor effects, a 15% BSA/HA solution constituting the bottoms of BMNs was chosen to load TMZ, showing sustained drug release for over 28 days, guaranteeing long-term DNA damage in TMZ-resistant cells (U251-TR). Needle tips made from 10% BSA/HA solution loaded with NIC released the drug within 14 days, enhancing TMZ's efficacy by inhibiting the activity of O6-methylguanine-DNA methyltransferase (MGMT). BMNs exhibit superior mechanical properties, bypass the BBB, and gradually release the drug into the tumor periphery, thus significantly inhibiting tumor proliferation and expanding median survival in mice. The on-demand delivery of BMNs patches shows a strong translational potential for clinical applications, particularly in synergistic GBM treatment.

Introduction: Lipid-based nanoparticles (LNPs) is increasingly recognized for their potential in drug delivery, offering protection to hydrophobic drugs from degradation. Industrial synthesis of LNPs, exemplified by Pfizer-BioNTech and Moderna mRNA vaccines, utilizes flow chemistry or microfluidics, showcasing its scalability. This study explores the utilization of a novel design reactor, the vortex tube reactor, within flow chemistry for LNPs synthesis, aiming to optimize its conditions and compare them with batch synthesis., Methods: LNPs were synthesized using the vortex tube reactor, incorporating bovine serum albumin (BSA) as a model drug in the aqueous phase, alongside 1.2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and cholesterol in the organic phase. Design of experiments (DoE), specifically Box-Behnken design, was employed to optimize parameters, including X 1 : the flow rate ratio (10-100 mL/min), X 2 : the aqueous-to-organic volumetric ratio (1:1-10:1), and X 3 : the number of reactor units (1-5 units). Responses evaluated encompassed physical properties and productivity. Optimized conditions were determined by minimizing particle size (Y 1 ), polydispersity index (Y 2 ), and zeta potential (Y 3 ), while maximizing entrapment efficiency (Y 4 ), drug loading (Y 5 ), and productivity (Y 5 )., Results: Results indicated that optimal conditions were achieved at X 1 of 100 mL/min, X 2 of 5.278, and X 3 of 1 unit. LNPs synthesized under these conditions exhibited favorable physical properties and productivity, with uniformity maintained across batches. The vortex tube reactor demonstrated superiority over batch synthesis, yielding smaller particles (166.23 ± 0.98 nm), more uniform nanoparticles (PDI 0.17 ± 0.01), and higher entrapment (67.75 ± 1.55%) and loading capacities (36.39 ± 0.83%), indicative of enhanced productivity (313.4 ± 12.88 mg/min)., Conclusion: This study elucidates the potential of flow chemistry, particularly utilizing the vortex tube reactor, for large-scale LNPs formulation, offering insights into parameter relationships and advancing nanoparticle synthesis for drug delivery applications., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Suwanpitak et al.)

The global demand for an enhanced quality of life and extended lifespan has driven significant advancements in tissue engineering and regenerative medicine. These fields utilize a range of interdisciplinary theories and techniques to repair structurally impaired or damaged tissues and organs, as well as restore their normal functions. Nevertheless, the clinical efficacy of medications, materials, and potent cells used at the laboratory level is always constrained by technological limitations. A novel platform known as adaptable microneedles has been developed to address the abovementioned issues. These microneedles offer a solution for the localized distribution of various cargos while minimizing invasiveness. Microneedles provide favorable patient compliance in clinical settings due to their effective administration and ability to provide a painless and convenient process. In this review article, we summarized the most recent development of microneedles, and we started by classifying various microneedle systems, advantages, and fundamental properties. Subsequently, it provides a comprehensive overview of different types of microneedles, the material used to fabricate microneedles, the fundamental properties of ideal microneedles, and their applications in tissue engineering and regenerative medicine, primarily focusing on preserving and restoring impaired tissues and organs. The limitations and perspectives have been discussed by concluding their future therapeutic applications in tissue engineering and regenerative medicines., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Background: High-flow nasal cannula (HFNC) systems employ different methods to provide aerosol to patients. This study compared delivery efficiency, particle size, and regional deposition of aerosolized bronchodilators during HFNC in neonatal, pediatric, and adult upper-airway and lung models between a proximal aerosol adapter and distal aerosol circuit chamber., Methods: A filter was connected to the upper airway to a spontaneously breathing lung model. Albuterol was nebulized using the aerosol adapter and circuit at different clinical flow settings. The aerosol mass deposited in the upper airway and lung was quantified. Particle size was measured with a laser diffractometer. Regional deposition was assessed with a gamma camera at each nebulizer location and patient model with minimum flow settings., Results: Inhaled lung doses ranged from 0.2-0.8% for neonates, 0.2-2.2% for the small child, and 0.5-5.2% for the adult models. Neonatal inhaled lung doses were not different between the aerosol circuit and adapter, but the aerosol circuit showed marginally greater lung doses in the pediatric and adult patient models. Impacted aerosols and condensation in the non-heated HFNC and aerosol delivery components contributed to the dispersion of coarse liquid droplets, high deposition (11-44%), and occlusion of the supine neonatal upper airway. In contrast, the upright pediatric and adult upper-airway models had minimal deposition (0.3-7.0%) and high fugitive losses (∼24%) from liquid droplets leaking out of the nose. The high impactive losses in the aerosol adapter (56%) were better contained than in the aerosol circuit, resulting in less cannula sputter (5% vs 22%), fewer fugitive losses (18% vs 24%), and smaller inhaled aerosols (5 µm vs 13 µm)., Conclusions: The inhaled lung dose was low (1-5%) during HFNC. Approaches that streamline aerosol delivery are needed to provide safe and effective therapy to patients receiving aerosolized medications with this HFNC system., Competing Interests: Mr DiBlasi discloses relationships with Medtronic, ABM Respiratory Care, Vapotherm, Dräger, and Aerogen Pharma. The remaining authors have disclosed no conflicts of interest., (Copyright © 2024 by Daedalus Enterprises.)

The mechanics of microneedle insertion have thus far been studied in a limited manner. Previous work has focused on buckling and failure of microneedle devices, while providing little insight into skin deformation, puncture, and the final positioning of needle tips under full microneedle arrays. The current study aims to develop a numerical approach capable of evaluating deformation and puncture conditions for full microneedle array designs. The analysis included a series of finite element submodels used to calibrate the microneedle-epidermal interface for failure properties using traction-separation laws. The single needle model is validated using experimental data and imaging, including results from a customized nanoindentation procedure to measure loads and displacements during microneedle insertion. Upon validation, full microneedle arrays are implemented in a 3 D finite element model and a design framework is developed, allowing evaluation of different design variables (i.e. needle shape, material, spacing) with respect to outputs relevant to successful microneedle performance. Results from the model include skin deformation, force to puncture, penetration depth, and the punctured state at each microneedle tip. In addition to microneedle parameters, patient parameters such as subcutaneous tissue thickness are included to evaluate the sensitivity of different microneedle designs to expected patient and anatomical region variability., (© PDA, Inc. 2024.)

Carbon monoxide (CO) has emerged as a promising therapeutic agent, yet ensuring safe and precise CO delivery remains challenging. Here, we report a removable hydrogel-forming microneedle (MN) reactor for CO delivery via photocatalysis, with an emphasis on chemosensitization. Upon application, body fluids absorbed by the MNs dissolve the effervescent agents, leading to the generation of carbon dioxide (CO 2 ) and triggering the release of the chemotherapeutics cisplatin. Meanwhile, the photocatalysts (PCs) trapped within MNs convert CO 2 to CO under 660 nm light irradiation. These PCs can be removed by hydrogel-forming MNs, thereby mitigating potential biological risks associated with residual PCs. Both in vitro and in vivo experiments showed that MN-mediated CO delivery significantly improved tumor sensitivity to cisplatin by suppressing DNA repair, using an A375/CDDP melanoma model. This removable photocatalysis MN reactor offers safe and precise local delivery of CO, potentially creating new opportunities for CO or its combination therapies.

Microrobots, which can perform tasks in difficult-to-reach parts of the human body under their own or external power supply, are potential tools for biomedical applications, such as drug delivery, microsurgery, imaging and monitoring, tissue engineering, and sensors and actuators. Compared with traditional fabrication methods for microrobots, recent improvements in 3D printers enable them to print high-precision microrobots, breaking through the limitations of traditional micromanufacturing technologies that require high skills for operators and greatly shortening the design-to-production cycle. Here, this review first introduces typical 3D printing technologies used in microrobot manufacturing. Then, the structures of microrobots with different functions and application scenarios are discussed. Next, we summarize the materials (body materials, propulsion materials and intelligent materials) used in 3D microrobot manufacturing to complete body construction and realize biomedical applications ( e.g. , drug delivery, imaging and monitoring). Finally, the challenges and future prospects of 3D printed microrobots in biomedical applications are discussed in terms of materials, manufacturing and advancement.

Neuropathic pain is a prevalent form of intermittent chronic pain, affecting approximately 7-10% of the global population. However, the current clinical administration methods, such as injection and oral administration, are mostly one-time administration, which cannot achieve accurate control of pain degree and drug dose. Herein, we developed near-infrared (NIR) light-responsive microneedle patches (MNPs) to spatiotemporally control the drug dose released to treat neuropathic pain according to the onset state. The mechanism of action utilizes upconversion nanoparticles to convert NIR light into visible and ultraviolet light. This conversion triggers the rapid rotation of the azobenzene molecular motor in the mesoporous material, enabling the on-demand controlled release of a drug dose. Additionally, MNs are used to overcome the barrier of the stratum corneum in a minimally invasive and painless manner, effectively promoting the transdermal penetration of drug molecules. The effectiveness of these patches has been demonstrated through significant results. Upon exposure to NIR light for five consecutive cycles, with each cycle lasting 30 s, the patches achieved a precise release of 318 μg of medication. In a mouse model, maximum pain relief was observed within 1 h of one cycle of NIR light exposure, with the effects lasting up to 6 h. The same level of precise treatment efficacy was maintained for subsequent pain episodes with similar light exposure. The NIR-controlled drugs precision-released MNPs provide a novel paradigm for the treatment of intermittent neuropathic pain.

Microneedles are a novel drug delivery system that offers advantages such as safety, painlessness, minimally invasive administration, simplicity of use, and controllable drug delivery. As a type of polymer microneedle with a three-dimensional network structure, hydrogel microneedles (HMNs) possess excellent biocompatibility and biodegradability and encapsulate various therapeutic drugs while maintaining drug activity, thus attracting significant attention. Recently, they have been widely employed to promote wound healing and have demonstrated favorable therapeutic effects. Although there are reviews about HMNs, few of them focus on wound management. Herein, we present a comprehensive overview of the design and preparation methods of HMNs, with a particular emphasis on their application status in wound healing, including acute wound healing, infected wound healing, diabetic wound healing, and scarless wound healing. Finally, we examine the advantages and limitations of HMNs in wound management and provide suggestions for future research directions.

A 3D-printed microfluidic tool for assessing local drug delivery systems (LDD) in simulated in vivo conditions was developed and evaluated. The device was designed considering the oral environment and dental applications, and it was fabricated with a high-precision resin 3D printer. Chitosan scaffolds loaded with different concentrations of doxycycline were used for evaluating our device. The concentration of the released drug was measured through in-line UV-VIS spectroscopy, and to verify the repeatability and accuracy of our measurements, comparisons with standard HPLC results were made (5% deviation). Cumulative drug release profiles in steady-state conditions were obtained and compared to the Weibull model. The behaviour of the LDD system in a dynamic environment was also evaluated during experiments where step changes in pH were introduced. It was demonstrated that under infection-like conditions, there is an immediate response from the polymer and a clear increase in the concentration of the released drug. Continuous flow and recirculation experiments were also conducted, revealing significant differences in the drug release profiles. Specifically, in the case of continuous flow, the quantity of the released drug is much higher due to the higher driving force for diffusion (concentration gradient). Overall, the proposed microfluidic tool proved to be ideal for evaluating LDD systems, as the in vivo microenvironment can be replicated in a better way than with currently used standard systems.

The nasal administration of therapeutic fluids and vaccines is used to treat allergic rhinitis, sinusitis, congestion, coronaviruses and even Alzheimer's disease. In the latter, the drug must reach the olfactory region, so it finds its way into the central nervous system. Effective administration techniques able to reach the olfactory region are challenging due to the tortuous anatomy of the nasal cavity, and are frequently evaluated in vitro using transparent anatomical models. Here, the liquid distribution inside a 3D printed human nasal cavity is quantified for model fluids resulting from the discharge of a 1-mL syringe with either a spray-generating nozzle, and a straight tip emitting a collimated fluid stream. Experiments using two model fluids with different viscosities suggest that a simple, correctly positioned straight tip attached to a syringe is able to efficiently deliver most of a therapeutic fluid in the human olfactory region in the side-laying position, avoiding the adoption of head-back and head-down positions that can be difficult for patients in the age range typical of Alzheimer's disease. Furthermore, we demonstrate by computer simulations that the conclusion is valid within a wide range of parameters., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Alopecia areata (AA) is a chronic autoimmune disease characterized by bald patches in certain areas of the body, especially the scalp. Minoxidil (MNX), as a first-line treatment of AA, effectively induces hair growth. However, oral and topical administration pose problems, including low bioavailability, risk of uncontrolled hair growth, and local side effects such as burning hair loss, and scalp irritation. In the latest research, MNX was delivered to the skin via microneedle (MN) transdermally. The MNX concentration was distributed throughout the needle so that drug penetration was reduced and had the potential to irritate. In this study, we formulated MNX into three-layer dissolving microneedles (TDMN) to increase drug penetration and avoid irritation. Physicochemical evaluation, parafilm, was used to evaluate the mechanical strength of TDMN and showed that TDMN could penetrate the stratum corneum. The ex-vivo permeation test showed that the highest average permeation result was obtained for TDMN2, namely 165.28 ± 31.87 ug/cm 2 , while for Minoxidil cream it was 46.03 ± 8.5 ug/cm 2 . The results of ex vivo and in vivo dermatokinetic tests showed that the amount of drug concentration remaining in the skin from the TDMN2 formula was higher compared to the cream preparation. The formula developed has no potential for irritation and toxicity based on the HET-CAM test and hemolysis test. TDMN is a promising alternative to administering MNX to overcome MNX problems and increase the effectiveness of AA therapy.

Due to the severity and high prevalence of cancer, as well as its complex pathological condition, new strategies for cancer treatment and diagnostics are required. As such, it is important to design a toolbox that integrates multiple functions on a single smart platform. Theranostic hydrogels offer an innovative and personalized method to tackle cancer while also considering patient comfort, thereby facilitating future implementation and translation to the clinic. In terms of theranostic systems used in cancer therapy, nanoparticles are widely used as diagnostic and therapeutic tools. Nanoparticles can achieve systemic circulation, evade host defenses, and deliver drugs and signaling agents at the targeted site, to diagnose and treat the disease at a cellular and molecular level. In this context, hydrogel microneedles have a high potential for multifunctional operation in medical devices, while avoiding the complications associated with the systemic delivery of therapeutics. Compared with oral administration and subcutaneous injection, microneedles offer advantages such as better patient compliance, faster onset of action, and improved permeability and efficacy. In addition, they comprise highly biocompatible polymers with excellent degradability and tunable properties. Nanoparticles and microneedles thus offer the possibility to expand the theranostic potential through combined synergistic use of their respective features. We review herein recent advances concerning processing methods and material requirements within the realm of hydrogel microneedles as theranostic platforms, various approaches toward cancer therapy, and the incorporation of nanoparticles for added functionality., (© 2024. The Author(s).)

Electrokinetic convection-enhanced delivery (ECED) utilizes an external electric field to drive the delivery of molecules and bioactive substances to local regions of the brain through electroosmosis and electrophoresis, without the need for an applied pressure. We characterize the implementation of ECED to direct a neutrally charged fluorophore (3 kDa) from a doped biocompatible acrylic acid/acrylamide hydrogel placed on the cortical surface. We compare fluorophore infusion profiles using ECED (time = 30 min, current = 50 µA) and diffusion-only control trials, for ex vivo (N = 18) and in vivo (N = 12) experiments. The linear intensity profile of infusion to the brain is significantly higher in ECED compared to control trials, both for in vivo and ex vivo. The linear distance of infusion, area of infusion, and the displacement of peak fluorescence intensity along the direction of infusion in ECED trials compared to control trials are significantly larger for in vivo trials, but not for ex vivo trials. These results demonstrate the effectiveness of ECED to direct a solute from a surface hydrogel towards inside the brain parenchyma based predominantly on the electroosmotic vector., (© 2024. The Author(s).)

Exosomes, as emerging "next-generation" biotherapeutics and drug delivery vectors, hold immense potential in diverse biomedical fields, ranging from drug delivery and regenerative medicine to disease diagnosis and tumor immunotherapy. However, the rapid clearance by traditional bolus injection and poor stability of exosomes restrict their clinical application. Microneedles serve as a solution that prolongs the residence time of exosomes at the administration site, thereby maintaining the drug concentration and facilitating sustained therapeutic effects. In addition, microneedles also possess the ability to maintain the stability of bioactive substances. Therefore, we introduce a microneedle patch for loading and delivering exosomes and share the methods, including isolation of exosomes, fabrication, and characterization of exosome-loaded microneedle patches. The microneedle patches were fabricated using trehalose and hyaluronic acid as the tip materials and polyvinylpyrrolidone as the backing material through a two-step casting method. The microneedles demonstrated robust mechanical strength, with tips able to withstand 2 N. Pig skin was used to simulate human skin, and the tips of microneedles completely melted within 60 s after skin puncture. The exosomes released from the microneedles exhibited morphology, particle size, marker proteins, and biological functions comparable to those of fresh exosomes, enabling dendritic cells uptake and promoting their maturation.

Introduction: Microneedles (MNs) are miniaturized, painless, and minimally invasive platforms that have attracted significant attention over recent decades across multiple fields, such as drug delivery, disease monitoring, disease diagnosis, and cosmetics. Several manufacturing methods have been employed to create MNs; however, these approaches come with drawbacks related to complicated, costly, and time-consuming fabrication processes. In this context, employing additive manufacturing (AM) technology for MN fabrication allows for the quick production of intricate MN prototypes with exceptional precision, providing the flexibility to customize MNs according to the desired shape and dimensions. Furthermore, AM demonstrates significant promise in the fabrication of sophisticated transdermal drug delivery systems and medical devices through the integration of MNs with various technologies., Areas Covered: This review offers an extensive overview of various AM technologies with great potential for the fabrication of MNs. Different types of MNs and the materials utilized in their fabrication are also discussed. Recent applications of 3D-printed MNs in the fields of transdermal drug delivery and biosensing are highlighted., Expert Opinion: This review also mentions the critical obstacles, including drug loading, biocompatibility, and regulatory requirements, which must be resolved to enable the mass-scale adoption of AM methods for MN production, and future trends.

In clinical treatments, reliable flow rate measurements ensure accurate drug delivery during infusions, precise gas delivery during artificial ventilations, etc., thereby reducing patient morbidity and mortality. However, precise flow rate sensors are costly, so medical devices with limited budgets choose cheaper but unsatisfactory flow rate measurement approaches, leading to increased medical risks. Here, a photoelectric flow rate sensor based on a flexible planar curved beam structure (FPCBS) is proposed. The FPCBS ensures low out-of-plane stiffness of the sensitive sheet and allows large deformation in the elastic range, enabling the flow rate sensor to measure the flow rate with high sensitivity over a wide range. Meanwhile, the flow rate sensor can be mass-produced using mature materials and manufacturing technology at less than $5 each. The flow rate sensors are integrated into a commercial infusion pump to measure drug infusion and a home ventilator to monitor respiration. The results are comparable to those measured by a commercial flow rate sensor, demonstrating the applicability of the sensor. Considering its proven outstanding performance at low cost, the flow rate sensor shows great potential in clinical treatment, medical diagnosis, and other medical fields., (© 2024 Wiley‐VCH GmbH.)

Analgesic creams find widespread application as adjuncts for localized anesthesia prior to surgical procedures. Nevertheless, the onset of analgesic action is protracted due to the skin barrier's inherent characteristics, which necessitates prolonged intervals of patient and clinician waiting, consequently impinging upon patient compliance and clinician workflow efficiency. In this work, a biodegradable microneedles (MNs) patch was introduced to enhance the intradermal administration of lidocaine cream to achieve rapid analgesia through a minimally invasive and conveniently accessible modality. The polylactic acid (PLA) MNs were mass-produced using a simple hot-pressing method and served the purpose of creating microchannels across the skin's surface for rapid absorption of lidocaine cream. Optical and electron microscopes were applied to meticulously scrutinize the morphology of the fabricated MNs, and the comprehensive penetration tests involving dynamometer tests, evaluation on porcine cadaver skin, artificial film, optical coherence tomography (OCT), transepidermal water loss, and analysis on rats' skins, demonstrated the robust mechanical strength of PLA MNs for successful intradermal penetration. The behavioral pain sensitivity tests on living rats using Von Frey hair filaments revealed that the MN-assisted lidocaine treatment expeditiously accelerated the onset of action from 40 to 10 min and substantially enhanced the efficacy of localized anesthesia. Furthermore, different treatment protocols encompassing the sequence of drug application relative to MN treatment, MN dimensions, and the frequency of MN insertions exhibited noteworthy influence on the resultant local anesthesia efficacy. Together, these results demonstrated that the lidocaine cream followed by diverse PLA MN treatments would be a promising strategy for rapid clinical local anesthesia with wide-ranging applications., (© 2024. Controlled Release Society.)

Ultrasonic microneedle patches, a class of ultrasound-driven transdermal drug delivery systems, are promising in addressing bacterial biofilms. This device has been proven to be more effective in treating Staphylococcus aureus biofilms than drug in free solution. However, there exists a notable gap in understanding how various excitation conditions and material parameters affect drug delivery efficiency. This study aims to fill this void by conducting an comprehensive multi-physics numerical analysis of ultrasonic microneedle patches, with the ultimate goal of enhancing drug delivery. First, we investigate the impact of various ultrasound frequencies on drug penetration depths. The findings reveal that local resonance can accelerate drug release within a shorter time window (first 1.5 h), whereas non-resonant frequencies enable more profound and prolonged diffusion. This information is crucial for medical professionals in selecting the most effective frequency for optimal drug administration. Furthermore, our investigation extends to the effects of applied voltage on temperature distribution, a critical aspect for ensuring medical safety during the application of these patches. Additionally, we examine how particles of different sizes respond to acoustic pressure and streaming fields, providing valuable insights for tailoring drug delivery strategies to specific therapeutic needs. Overall, our findings offer comprehensive guidelines for the effective use of ultrasonic microneedle patches, potentially shifting the paradigm in patient care and enhancing the overall quality of life., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: To examine the effects of percutaneous tetracycline delivery to the malar area using a thermomechanical device (Tixel) in patients suffering from festoons., Methods: This retrospective study included patients who underwent combination treatment with a thermomechanical device (Tixel) followed by application of topical tetracycline 1% at two private clinics between 2019 and 2023. Demographic and medical data, treatment parameters along with before and after treatment photographs were retrieved retrospectively. All patients were asked to answer a questionnaire, assessing self-reported pre and posttreatment disturbance, patient global impression of change (PGIC) score, overall satisfaction with treatment, and the onset and duration of treatment effect. Finally, three masked reviewers evaluated and graded the severity of before and after treatment photographs., Results: Twenty healthy patients received the combination treatment. The mean age was 59.4 ± 8.2 years (range: 45-72 years), and 90.0% (n = 18) were female. The number of treatment sessions per patient ranged from 2 to 8, mean of 5.0 ± 1.9, performed at 5.4 ± 1.2-week intervals. The masked reviewers' grading scores demonstrated a significant improvement (2.81 ± 1.3 before vs. 1.6 ± 1.1 after, p < 0.001). The self-reported disturbance caused by the festoons improved significantly as well (4.7 ± 0.98 vs. 1.7 ± 1.1, p < 0.001). On the PGIC score, 85% (17/20) reported moderate (grade 5) to significant (grade 7) improvement of symptoms and life quality after treatment. Improvement onset was reported to occur 11.2 ± 6.6 days after the first treatment (range 2-30 days), and 90% (18/20) of the patients reported improvement lasting at least 4 months after completion of the second treatment., Conclusions: Topical tetracycline application following Tixel treatment induced significant improvement in patient with festoons., (© 2024 Wiley Periodicals LLC.)

Diclofenac, a nonsteroidal anti-inflammatory drug, is commonly prescribed for managing osteoarthritis, rheumatoid arthritis, and post-surgical pain. However, oral administration of diclofenac often leads to adverse effects. This study introduces an innovative nano-in-micro approach to create diclofenac nanoparticle-loaded microneedle patches aimed at localised, sustained pain relief, circumventing the drawbacks of oral delivery. The nanoparticles were produced via wet-milling, achieving an average size of 200 nm, and then incorporated into microneedle patches. These patches showed improved skin penetration in ex vivo tests using Franz-cell setups compared to traditional diclofenac formulations. In vivo tests on rats revealed that the nanoparticle-loaded microneedle patches allowed for quick drug uptake and prolonged release, maintaining drug levels in tissues for up to 72 h. With a systemic bioavailability of 57 %, these patches prove to be an effective means of transdermal drug delivery. This study highlights the potential of this novel microneedle delivery system in enhancing the treatment of chronic pain with reduced systemic side effects., Competing Interests: Declaration of competing interest Ryan Donnelly is an inventor of patents that have been licenced to companies developing microneedle-based products and is a paid advisor to companies developing microneedle-based products. The resulting potential conflict of interest has been disclosed and is managed by Queen's University Belfast. The companies had no role in the design of the present studies, in the collection, analyses or interpretation of the data, in the writing of the manuscript or in the decision to publish the work. Other all authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Wearable epidermal electronics with non- or minimally-invasive characteristics can collect, transduce, communicate, and interact with accessible physicochemical health indicators on the skin. However, due to the stratum corneum layer, rich information about body health is buried under the skin stratum corneum layer, for example, in the skin interstitial fluid. Microneedle patches are typically designed with arrays of special microsized needles of length within 1000 µm. Such characteristics potentially enable the access and sample of biomolecules under the skin or give therapeutical treatment painlessly and transdermally. Integrating microneedle patches with various electronics allows highly efficient transdermal bioelectronics, showing their great promise for biomedical and healthcare applications. This comprehensive review summarizes and highlights the recent progress on integrated transdermal bioelectronics based on microneedle patches. The design criteria and state-of-the-art fabrication techniques for such devices are initially discussed. Next, devices with different functions, including but not limited to health monitoring, drug delivery, and therapeutical treatment, are highlighted in detail. Finally, key issues associated with current technologies and future opportunities are elaborated to sort out the state of recent research, point out potential bottlenecks, and provide future research directions., (© 2024 Wiley‐VCH GmbH.)

Drug delivery systems, where the nanofluid flow with electroosmosis and mixed convection can help in efficient and targeted drug delivery to specific cells or organs, could benefit from understanding the behavior of nanofluids in biological systems. In current work, authors have studied the theoretical model of two-dimensional ciliary flow of blood-based (Eyring-Powell) nanofluid model with the insertion of ternary hybrid nanoparticles along with the effects of electroosmosis, magnetohydrodynamics, thermal radiations, and mixed convection. Moreover, the features of entropy generation are also taken into consideration. The system is modeled in a wave frame with the approximations of large wave number and neglecting turbulence effects. The problem is solved numerically by using the shooting method with the assistance of computational software "Mathematica" for solving the governing equation. According to the temperature curves, the temperature will increase as the Hartman number, fluid factor, ohmic heating, and cilia length increase. It is also disclosed that ternary hybrid nanoparticles result in a change in flow rate when other problem parameters are varied, and the same is true for temperature graphs. Engineers and scientists can make better use of nanofluid-based cooling systems in electronics, automobiles, and industrial processes with the aid of the study's findings., (© 2023 Wiley‐VCH GmbH.)

Automated delivery of insulin based on continuous glucose monitoring is revolutionizing the way insulin-dependent diabetes is treated. However, challenges remain for the widespread adoption of these systems, including the requirement of a separate glucose sensor, sophisticated electronics and algorithms, and the need for significant user input to operate these costly therapies. Herein, a user-centric glucose-responsive cannula is reported for electronics-free insulin delivery. The cannula-made from a tough, elastomer-hydrogel hybrid membrane formed through a one-pot solvent exchange method-changes permeability to release insulin rapidly upon physiologically relevant varying glucose levels, providing simple and automated insulin delivery with no additional hardware or software. Two prototypes of the cannula are evaluated in insulin-deficient diabetic mice. The first cannula-an ends-sealed, subcutaneously inserted prototype-normalizes blood glucose levels for 3 d and controls postprandial glucose levels. The second, more translational version-a cannula with the distal end sealed and the proximal end connected to a transcutaneous injection port-likewise demonstrates tight, 3-d regulation of blood glucose levels when refilled twice daily. This proof-of-concept study may aid in the development of "smart" cannulas and next-generation insulin therapies at a reduced burden-of-care toll and cost to end-users., (© 2024 Wiley‐VCH GmbH.)

Background: Optimal aerosol delivery methods for spontaneously breathing patients with a tracheostomy remain unclear. Thus, we aimed to assess the impact of nebulizer placement, flow settings, and interfaces on aerosol delivery by using a vibrating mesh nebulizer and a jet nebulizer in line with unheated humidification., Methods: An 8.0-mm tracheostomy tube was connected to the lung model that simulates adult breathing parameters via a collecting filter. Albuterol sulfate (2.5 mg/3 mL) was administered via a vibrating mesh nebulizer and a jet nebulizer, which was placed in line with unheated humidification provided by a large-volume nebulizer, with F IO 2 set at 0.28, with gas flows of 2 L/min versus 6 L/min. Nebulizers were placed in line distal and proximal to the lung model by using a tracheostomy collar and a T-piece. Conventional nebulization was tested using a vibrating mesh nebulizer and a jet nebulizer directly connected to the tracheostomy tube bypassing the humidification device. The drug was eluted from the collecting filter and assayed with ultraviolet spectrophotometry (276 nm)., Results: During in-line nebulizer placement with unheated humidification, the inhaled dose was 2-4 times higher with a gas flow of 2 L/min than 6 L/min, regardless of nebulizer type, placement, or interface (all P < .05). At 6 L/min, the inhaled dose was higher with proximal than distal placement when using both interfaces, but, at 2 L/min, the inhaled dose was lower with proximal placement. With a jet nebulizer, the tracheostomy collar generated a higher inhaled dose at proximal placement compared with the T-piece, whereas the T-piece resulted in a higher inhaled dose than the tracheostomy collar with distal placement, regardless of the flow settings. Compared with conventional nebulization using a vibrating mesh nebulizer, an in-line vibrating mesh nebulizer with a large-volume nebulizer at 2 L/min had a similar inhaled dose, regardless of nebulizer placement and interface. In contrast, the in-line jet nebulizer was influenced by both placement and interface., Conclusions: Aerosol delivery with an in-line vibrating mesh nebulizer and jet nebulizer with unheated humidification was affected by nebulizer placement, interface, and gas flow settings., Competing Interests: Dr Li discloses relationships with Fisher & Paykel Healthcare, Aerogen, the Rice Foundation, the American Association for Respiratory Care, and Heyer; and is section editor for Respiratory Care. Ms Albuainain has disclosed no conflicts of interest., (Copyright © 2024 by Daedalus Enterprises.)

On-demand drug delivery holds great promise to optimize pharmaceutical efficacy while minimizing the side effects. However, existing on-demand drug delivery systems often require complicated manufacturing processes that preclude their wide implementation of a broad range of drugs. In this work, we demonstrate the introduction of MXene-coated microneedles (MNs) into bioelectronics for digitally controllable gate-valve drug delivery. MXenes, featuring high electronic conductivity, excellent biocompatibility, and solution processibility, enable low-cost scalability for printable bioelectronics. In an electrolytic state ( e.g. , body fluid), the coated MXene is oxidized and desorbed due to redox reactions caused by electrical bias, allowing the underlying drug to be controllably released. The MXene-incorporated drug delivery system not only demonstrates excellent biocompatibility and operational stability, but also features low-cost construction and sustainable usage. Besides, these MXene-coated MNs allow both on-demand transformation and local-region customization, further increasing the structural versatility and capability of multidrug delivery systems.

Background: In recent years, an increasing number of patient-reported outcome assessment tools (PROs) have been developed specifically to ascertain patients' perceptions of different drug treatments. Among them, the injection process has been analysed, especially in patients chronically treated with chronic biological therapies. One of the main advantages of most current biological therapies is the possibility to self-administer medication at home through the use of a variety of devices, including prefilled syringes (PFS) and prefilled pens (PFP)., Objectives: The aim of this study was to conduct qualitative research to assess the degree of preference between the different pharmaceutical forms PFS and PFP., Methods: We performed a cross-sectional observational study in patients on biological drug therapy through the compilation of a web-based questionnaire at the time of routine delivery of biological therapy. Questions regarding primary diagnosis, adherence to therapy, the preferred pharmaceutical form and the main reason for preference among five possibilities already reported in the scientific literature were included., Results: During the study period, data were collected from 111 patients and 68 (58%) indicated PFP as their preference. From the analysis of reasons that led a patient to choose one device over another, PFSs are chosen mainly out of habit (n=13 (28.3%) PFS vs n=2 (3.1%) PFP) while PFPs are chosen to avoid needle vision (n=15 (23.1%) PFP vs n=1 (2.2%) PFS). Both differences were found to be statistically significant (p<0.001)., Conclusion: As biological subcutaneous drugs are increasingly prescribed for a wide variety of long-term therapies, further research focused on identifying patient factors which may enhance adherence to treatment will become even more valuable., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

A novel therapeutic approach combining acupuncture and diclofenac sodium (DS) administration was established for the potential treatment for rheumatoid arthritis (RA). DS is a commonly used anti-inflammatory and analgesic drug but has short duration and adverse effects. Acupoints are critical linkages in the meridian system and are potential candidates for drug delivery. Herein, we fabricated a DS-loaded multilayer-modified acupuncture needle (DS-MMAN) and investigated its capacity for inhibiting RA. This DS-MMAN possesses sustained release properties and in vitro anti-inflammatory effects. Experimental results showed that the DS-MMAN with microdoses can enhance analgesia and efficiently relieve joint swelling compared to the oral or intra-articular administration of DS with gram-level doses. Moreover, the combination of acupoint and DS exerts a synergistic improvement in inflammation and joint damage. Cytokine and T cell analyses in the serum indicated that the application of DS-MMAN suppressed the levels of pro-inflammatory factors and increased the levels of anti-inflammatory factors. Furthermore, the acupoint administration via DS-MMAN could decrease the accumulation of DS in the liver and kidneys, which may express better therapeutic efficiency and low toxicity. The present study demonstrated that the acupuncture needle has the potential to build a bridge between acupuncture and medication, which would be a promising alternative to the combination of traditional and modern medicine.

In this work, microspheres were developed by cross-linking glutaraldehyde in an aqueous gelatin solution with a surfactant and solvent. A poly(vinyl alcohol) (PVA) solution was produced and combined with catechin-loaded microspheres. Different microsphere concentrations (0%, 5%, 10%, and 15%) were applied to the PVA microneedles. The moisture content, particle size, swelling, and drug release percentage of microneedles were studied using various microsphere concentrations. Fourier transform infrared and scanning electron microscopy (SEM) investigations validated the structure of gelatin microspheres as well as their decoration in microneedles. The SEM scans revealed that spherical microspheres with a wrinkled and folded morphology were created, with no physical holes visible on the surface. The gelatin microspheres generated had a mean particle size of 20-30 μm. Ex vivo release analysis indicated that microneedles containing 10% microspheres released the most catechin, with 42.9% at 12 h and 84.4% at 24 h.

Microneedles (MNs) are micron-scale needles that are a painless alternative to injections for delivering drugs through the skin. MNs find applications as biosensing devices and could serve as real-time diagnosis tools. There have been numerous fabrication techniques employed for producing quality MN-based systems, prominent among them is the three-dimensional (3D) printing. 3D printing enables the production of quality MNs of tuneable characteristics using a variety of materials. Further, the possible integration of artificial intelligence (AI) tools such as machine learning (ML) and deep learning (DL) with 3D printing makes it an indispensable tool for fabricating microneedles. Provided that these AI tools can be trained and act with minimal human intervention to control the quality of products produced, there is also a possibility of mass production of MNs using these tools in the future. This work reviews the specific role of AI in the 3D printing of MN-based devices discussing the use of AI in predicting drug release patterns, its role as a quality control tool, and in predicting the biomarker levels. Additionally, the autonomous 3D printing of microneedles using an integrated system of the internet of things (IoT) and machine learning (ML) is discussed in brief. Different categories of machine learning including supervised learning, semi-supervised learning, unsupervised learning, and reinforced learning have been discussed in brief. Lastly, a brief section is dedicated to the biosensing applications of MN-based devices., (© 2024. Controlled Release Society.)

In recent year, the research of transdermal drug delivery systems has got substantial attention towards the development of microneedles (MNs). This shift has occurred due to multifaceted advantages of MNs as they can be utilized to deliver the drug deeper to the skin with minimal invasion, offer successful delivery of drugs and biomolecules that are susceptible to degradation in gastrointestinal tract (GIT), act as biosensors, and help in monitoring the level of biomarkers in the body. These can be fabricated into different types based on their applications as well as material for fabrication. Some of their types include solid MNs, hollow MNs, coated MNs, hydrogel forming MNs, and dissolving MNs. These MNs deliver the therapeutics via microchannels deeper into the skin. The coated and hollow MNs have been found successful. However, they suffer from poor drug loading and blocking of pores. In contrast, dissolving MNs offer high drug loading. These MNs have also been utilized to deliver vaccines and biologicals. They have also been used in cosmetics. The current review covers the different types of MNs, materials used in their fabrication, properties of MNs, and various case studies related to their role in delivering therapeutics, monitoring level of biomarkers/hormones in body such as insulin. Various patents and clinical trials related to MNs are also covered. Covered are the major bottlenecks associated with their clinical translation and potential future perspectives., (© 2023. Controlled Release Society.)

Cancer, namely breast and prostate cancers, is the leading cause of death in many developed countries. Controlled drug delivery systems are key for the development of new cancer treatment strategies, to improve the effectiveness of chemotherapy and tackle off-target effects. In here, we developed a biomaterials-based wireless electrostimulation system with the potential for controlled and on-demand release of anti-cancer drugs. The system is composed of curcumin-loaded poly(3,4-ethylenedioxythiophene) nanoparticles (CUR/PEDOT NPs), encapsulated inside coaxial poly(glycerol sebacate)/poly(caprolactone) (PGS/PCL) electrospun fibers. First, we show that the PGS/PCL nanofibers are biodegradable, which allows the delivery of NPs closer to the tumoral region, and have good mechanical properties, allowing the prolonged storage of the PEDOT NPs before their gradual release. Next, we demonstrate PEDOT/CUR nanoparticles can release CUR on-demand (65 % of release after applying a potential of -1.5 V for 180 s). Finally, a wireless electrostimulation platform using this NP/fiber system was set up to promote in vitro human prostate cancer cell death. We found a decrease of 67 % decrease in cancer cell viability. Overall, our results show the developed NP/fiber system has the potential to effectively deliver CUR in a highly controlled way to breast and prostate cancer in vitro models. We also show the potential of using wireless electrostimulation of drug-loaded NPs for cancer treatment, while using safe voltages for the human body. We believe our work is a stepping stone for the design and development of biomaterial-based future smarter and more effective delivery systems for anti-cancer therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Some experts recommend specific ventilator settings during nebulization for mechanically ventilated patients, such as inspiratory pause, high inspiratory to expiratory ratio, and so on. However, it is unclear whether those settings improve aerosol delivery. Thus, we aimed to evaluate the impact of ventilator settings on aerosol delivery during mechanical ventilation (MV). Methods: Salbutamol (5.0 mg/2.5 mL) was nebulized by a vibrating mesh nebulizer (VMN) in an adult MV model. VMN was placed at the inlet of humidifier and 15 cm away from the Y-piece of the inspiratory limb. Eight scenarios with different ventilator settings were compared with endotracheal tube (ETT) connecting 15 cm from the Y-piece, including tidal volumes of 6-8 mL/kg, respiratory rates of 12-20 breaths/min, inspiratory time of 1.0-2.5 seconds, inspiratory pause of 0-0.3 seconds, and bias flow of 3.5 L/min. In-line suction catheter was utilized in two scenarios. Delivered drug distal to the ETT was collected by a filter, and drug was assayed by an ultraviolet spectrophotometry (276 nm). Results: Compared to the use of inspiratory pause, the inhaled dose without inspiratory pause was either higher or similar across all ventilation settings. Inhaled dose was negatively correlated with inspiratory flow with VMN placed at 15 cm away from the Y-piece ( r s  = -0.68, p  < 0.001) and at the inlet of humidifier ( r s  = -0.83, p  < 0.001). The utilization of in-line suction catheter reduced inhaled dose, regardless of the ventilator settings and nebulizer placements. Conclusions: When VMN was placed at the inlet of humidifier, directly connecting the Y-piece to ETT without a suction catheter improved aerosol delivery. In this configuration, the inhaled dose increased as the inspiratory flow decreased, inspiratory pause had either no or a negative impact on aerosol delivery. The inhaled dose was greater with VMN placed at the inlet of humidifier than 15 cm away the Y-piece.

Microneedles offer minimally invasive, user-friendly, and subcutaneously accessible transdermal drug delivery and have been widely investigated as an effective transdermal delivery system. Ibuprofen is a common anti-inflammatory drug to treat chronic inflammation. It is crucial to develop microneedle patches capable of efficiently delivering ibuprofen through the skin for the effective treatment of arthritis patients requiring repeated medication. In this study, the mechanical properties of a new type of polymer microneedle were studied by finite element analysis, and the experimental results showed that the microneedle could effectively deliver drugs through the skin. In addition, a high ibuprofen-loaded microneedle patch was successfully prepared by micromolding and subjected to evaluation of its infrared spectrum morphology and dissolve degree. The morphology of microneedles was characterized by scanning electron microscopy, and the mechanical properties were assessed using a built linear stretching system. In the in-vitro diffusion cell drug release test, the microneedle released 85.2 ± 1.52% (210 ± 3.7 μg) ibuprofen in the modified Franz diffusion within 4 h, exhibiting a higher drug release compared to other drug delivery methods. This study provides a portable, safe and efficient treatment approach for arthritis patients requiring daily repeated medication.

Background: Acne vulgaris often results in permanent scars, with atrophic scars being the most common type and posing a significant therapeutic challenge due to their prevalence and impact on patients' quality of life. Various treatment options exist, including the use of poly-d,l-lactic acid delivered via different methods., Objective: This study aimed to assess the efficacy and safety of poly-d,l-lactic acid delivered via laser-assisted needle-free microjet injection for treating atrophic scars., Methods: Five Korean participants with atrophic facial scars were recruited. Poly-d,l-lactic acid solution was administered via the Mirajet system in five sessions, with clinical assessments conducted at baseline, before each session, and at 12-week and 22-week follow-ups. Outcome measures included the Global Aesthetic Improvement Scale and patient satisfaction scores., Results: Positive results were observed at the 12-week and 22-week follow-ups, with high patient satisfaction and improvements in atrophic scars and skin texture. Mild discomfort and transient side effects were reported, with no adverse events observed during the follow-up period., Conclusion: Poly-d,l-lactic acid delivered by a laser-assisted needle-free microjet injector was judged to be effective for improving atrophic the facial area. Further research, particularly through randomized controlled trials, is needed to validate these findings and assess the longer-term safety and sustainability of outcomes., (© 2024 The Author(s). Skin Research and Technology published by John Wiley & Sons Ltd.)

Bioanalyte collection by blood draw is a painful process, prone to needle phobia and injuries. Microneedles can be engineered to penetrate the epidermal skin barrier and collect analytes from the interstitial fluid, arising as a safe, painless, and effective alternative to hypodermic needles. Although there are plenty of reviews on the various types of microneedles and their use as drug delivery systems, there is a lack of systematization on the application of polymeric microneedles for diagnosis. In this review, we focus on the current state of the art of this field, while providing information on safety, preclinical and clinical trials, and market distribution, to outline what we believe will be the future of health monitoring.

The advancement of science and technology, coupled with the growing environmental consciousness among individuals, has led to a shift in pesticide development from traditional methods characterized by inefficiency and misuse toward a more sustainable and eco-friendly approach. Cellulose, as the most abundant natural renewable resource, has opened up a new avenue in the field of biobased drug carriers by developing cellulose-based drug delivery systems. These systems offer unique advantages in terms of deposition rate enhancement, modification facilitation, and environmental impact reduction when designing nanopesticides. Consequently, their application in the field of nanoscale pesticides has gained widespread recognition. The present study provides a comprehensive review of cellulose modification methods, carrier types for cellulose-based nanopesticides delivery systems (CPDS), and various stimulus-response factors influencing pesticide release. Additionally, the main challenges in the design and application of CPDS are summarized, highlighting the immense potential of cellulose-based materials in the field of nanopesticides.

Precision medicine endeavors to personalize treatments, considering individual variations in patient responses based on factors like genetic mutations, age, and diet. Integrating this approach dynamically, bioelectronics equipped with real-time sensing and intelligent actuation present a promising avenue. Devices such as ion pumps hold potential for precise therapeutic drug delivery, a pivotal aspect of effective precision medicine. However, implementing bioelectronic devices in precision medicine encounters formidable challenges. Variability in device performance due to fabrication inconsistencies and operational limitations, including voltage saturation, presents significant hurdles. To address this, closed-loop control with adaptive capabilities and explicit handling of saturation becomes imperative. Our research introduces an enhanced sliding mode controller capable of managing saturation, adept at satisfactory control actions amidst model uncertainties. To evaluate the controller's effectiveness, we conducted in silico experiments using an extended mathematical model of the proton pump. Subsequently, we compared the performance of our developed controller with classical Proportional Integral Derivative (PID) and machine learning (ML)-based controllers. Furthermore, in vitro experiments assessed the controller's efficacy using various reference signals for controlled Fluoxetine delivery. These experiments showcased consistent performance across diverse input signals, maintaining the current value near the reference with a relative error of less than 7% in all trials. Our findings underscore the potential of the developed controller to address challenges in bioelectronic device implementation, offering reliable precision in drug delivery strategies within the realm of precision medicine., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Marquez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Persistent foot odor and itchiness are common symptoms of tinea pedis, significantly disrupting the daily life of those affected. The cuticular barrier at the site of the tinea pedis is thickened, which impedes the effective penetration of antifungal agents. Additionally, fungi can migrate from the skin surface to deeper tissues, posing challenges in the current clinical treatment for tinea pedis. To effectively treat tinea pedis, we developed a platform of bilayer gelatin methacrylate (GelMA) microneedles (MNs) loaded with salicylic acid (SA) and FK13-a1 (SA/FK13-a1@GelMA MNs). SA/FK13-a1@GelMA MNs exhibit pH- and matrix metalloproteinase (MMP)-responsive properties for efficient drug delivery. The MNs are designed to deliver salicylic acid (SA) deep into the stratum corneum, softening the cuticle and creating microchannels. This process enables the antibacterial peptide FK13-a1 to penetrate through the stratum corneum barrier, facilitating intradermal diffusion and exerting antifungal and anti-inflammatory effects. In severe cases of tinea pedis, heightened local pH levels and MMP activity further accelerate drug release. Our research demonstrates that SA/FK13-a1@GelMA MNs are highly effective against Trichophyton mentagrophytes , Trichophyton rubrum , and Candida albicans . They also reduced stratum corneum thickness, fungal burden, and inflammation in a guinea pig model of tinea pedis induced by T. mentagrophytes . Furthermore, it was discovered that SA/FK13-a1@GelMA MNs exhibit excellent biocompatibility. These findings suggest that SA/FK13-a1@GelMA MNs have significant potential for the clinical treatment of tinea pedis as well as other fungal skin disorders.

The timely administration of glucagon is a standard clinical practice for the treatment of severe hypoglycemia. However, the process involves cumbersome steps, including the reconstitution of labile glucagon and filling of the syringe, which cause considerable delays in emergency situations. Moreover, multiple dosages are often required to prevent the recurrence of the hypoglycemic episode because of the short half-life of glucagon in plasma. Herein, we develop a glucagon-loaded long-dissolving microneedle (GLMN) patch that exhibits the properties of fast onset and sustained activity for the effective treatment of severe hypoglycemia. Three types of MN patches were fabricated with different dimensions (long, medium, and short). The longer MN patch packaged a higher dosage of glucagon and exhibited supreme mechanical strength compared to the shorter one. Additionally, the longer MN patch could insert more deeply into the skin, resulting in higher permeability of glucagon across the skin tissue and more rapid systemic absorption as compared with the shorter MN patch. The GLMN patch was observed to reverse the effects of hypoglycemia within 15 min of application in animal models (specifically, rat and rhesus monkey models) and maintained long-term glycemic control, owing to highly efficient drug permeation and the drug reservoir effect of the MN base. The current study presents a promising strategy for the rapid reversal of severe hypoglycemia that exhibits the desirable properties of easy use, high efficiency, and sustained action.

Rheumatoid arthritis (RA) is a global autoimmune disease that requires long-term management. Ambulatory monitoring and treatment of RA favors remission and rehabilitation. Here, we developed a wearable reconfigurable integrated smart device (ISD) for real-time inflammatory monitoring and synergistic therapy of RA. The device establishes an electrical-coupling and substance delivery interfaces with the skin through template-free conductive polymer microneedles that exhibit high capacitance, low impedance, and appropriate mechanical properties. The reconfigurable electronics drive the microneedle-skin interfaces to monitor tissue impedance and on-demand drug delivery. Studies in vitro demonstrated the anti-inflammatory effect of electrical stimulation on macrophages and revealed the molecular mechanism. In a rodent model, impedance sensing was validated to hint inflammation condition and facilitate diagnosis through machine learning model. The outcome of subsequent synergistic therapy showed notable relief of symptoms, elimination of synovial inflammation, and avoidance of bone destruction.