Transcutaneous Delivery of Dexamethasone Sodium Phosphate Via Microneedle-Assisted Iontophoretic Enhancement - A Potential Therapeutic Option for Inflammatory Disorders.

AIM: This study aimed to fabricate dexamethasone sodium phosphate loaded microneedle arrays (MNA) and investigate their efficiency in combination with iontophoresis for the treatment of hind paw oedema in rats. METHODS: Drug loaded polyvinyl alcohol, polyvinyl pyrrolidone and D-sorbitol-based MNA11 were fabricated by vacuum micromolding. Physicochemical, morphological, thermal, in-silico, in-vitro insertion ability (on parafilm) and drug release studies were performed. Ex-vivo permeation, in-vivo insertion and anti-inflammatory studies were performed in combination with iontophoresis. RESULTS: MNA11 displayed sharp-tipped projections and acceptable physicochemical features. Differential scanning calorimetry results indicated that drug loaded MNA11 were amorphous solids. Drug interacted with PVP and PVA predominately via hydrogen bonding. Parafilm displayed conspicuously engraved complementary structure of MNA11. Within 60 min, 91.50 ± 3.1% drug released from MNA11. A significantly higher i.e., 95.06 ± 2.5% permeation of drug was observed rapidly (within 60 min) from MNA11-iontophoresis combination than MNA11 i.e., 84.07 ± 3.5% within 240 min. Rat skin treated using MNA11 and MNA11-iontophoresis showed disruptions / microchannels in the epidermis without any damage to underlying anatomical structures. MNA11-iontophoresis combination led to significant reduction (83.02 ± 3.9%) in paw oedema as compared to MNA11 alone (72.55 ± 4.1%). CONCLUSION: MNA11-iontophoresis combination can act as a promising candidate to deliver drugs transcutaneously for treating inflammatory diseases.

Remote-Controlled Sensing and Drug Delivery via 3D-Printed Hollow Microneedles.

Remote health monitoring and treatment serve as critical drivers for advancing health equity, bridging geographical and socioeconomic disparities, ensuring equitable access to quality healthcare for those in underserved or remote regions. By democratizing healthcare, this approach offers timely interventions, continuous monitoring, and personalized care independent of one's location or socioeconomic status, thereby striving for an equitable distribution of health resources and outcomes. Meanwhile, microneedle arrays (MNAs), revolutionize painless and minimally invasive access to interstitial fluid for drug delivery and diagnostics. This paper introduces an integrated theranostic MNA system employing an array of colorimetric sensors to quantitatively measure -pH, glucose, and lactate, alongside a remotely-triggered system enabling on-demand drug delivery. Integration of an ultrasonic atomizer streamlines the drug delivery, facilitating rapid, pumpless, and point-of-care drug delivery, enhancing system portability while reducing complexities. An accompanying smartphone application interfaces the sensing and drug delivery components. Demonstrated capabilities include detecting pH (3 to 8), glucose (up to 16 mm), and lactate (up to 1.6 mm), showcasing on-demand drug delivery, and assessing delivery system performance via a scratch assay. This innovative approach confronts drug delivery challenges, particularly in managing chronic diseases requiring long-term treatment, while also offering avenues for non-invasive health monitoring through microneedle-based sensors.

GEOMETRIC DETERMINANTS OF CELL VIABILITY FOR 3D-PRINTED HOLLOW MICRONEEDLE ARRAY-MEDIATED DELIVERY.

A wide range of emerging biomedical applications and clinical interventions rely on the ability to deliver living cells via hollow, high-aspect-ratio microneedles. Recently, microneedle arrays (MNA) have gained increasing interest due to inherent benefits for drug delivery; however, studies exploring the potential to harness such advantages for cell delivery have been impeded due to the difficulties in manufacturing high-aspect-ratio MNAs suitable for delivering mammalian cells. To bypass these challenges, here we leverage and extend our previously reported hybrid additive manufacturing (or "three-dimensional (3D) printing) strategy-i.e., the combined the "Vat Photopolymerization (VPP)" technique, "Liquid Crystal Display (LCD)" 3D printing with "Two-Photon Direct Laser Writing (DLW)"-to 3D print hollow MNAs that are suitable for cell delivery investigations. Specifically, we 3D printed four sets of 650 µm-tall MNAs corresponding to needle-specific inner diameters (IDs) of 25 µm, 50 µm, 75 µm, and 100 µm, and then examined the effects of these MNAs on the post-delivery viability of both dendritic cells (DCs) and HEK293 cells. Experimental results revealed that the 25 µm-ID case led to a statistically significant reduction in post-MNA-delivery cell viability for both cell types; however, MNAs with needle-specific IDs ≥ 50 µm were statistically indistinguishable from one another as well as conventional 32G single needles, thereby providing an important benchmark for MNA-mediated cell delivery.

Technological Advances of Wearable Device for Continuous Monitoring of In Vivo Glucose.

Managing diabetes is a chronic challenge today, requiring monitoring and timely insulin injections to maintain stable blood glucose levels. Traditional clinical testing relies on fingertip or venous blood collection, which has facilitated the emergence of continuous glucose monitoring (CGM) technology to address data limitations. Continuous glucose monitoring technology is recognized for tracking long-term blood glucose fluctuations, and its development, particularly in wearable devices, has given rise to compact and portable continuous glucose monitoring devices, which facilitates the measurement of blood glucose and adjustment of medication. This review introduces the development of wearable CGM-based technologies, including noninvasive methods using body fluids and invasive methods using implantable electrodes. The advantages and disadvantages of these approaches are discussed as well as the use of microneedle arrays in minimally invasive CGM. Microneedle arrays allow for painless transdermal puncture and are expected to facilitate the development of wearable CGM devices. Finally, we discuss the challenges and opportunities and look forward to the biomedical applications and future directions of wearable CGM-based technologies in biological research.

MiR-141-3p-Functionalized Exosomes Loaded in Dissolvable Microneedle Arrays for Hypertrophic Scar Treatment.

Hypertrophic scar (HS) is a common fibroproliferative disease caused by abnormal wound healing after deep skin injury. However, the existing approaches have unsatisfactory therapeutic effects, which promote the exploration of newer and more effective strategies. MiRNA-modified functional exosomes delivered by dissolvable microneedle arrays (DMNAs) are expected to provide new hope for HS treatment. In this study, a miRNA, miR-141-3p, which is downregulated in skin scar tissues and in hypertrophic scar fibroblasts (HSFs), is identified. MiR-141-3p mimics inhibit the proliferation, migration, and myofibroblast transdifferentiation of HSFs in vitro by targeting TGF-ß2 to suppress the TGF-ß2/Smad pathway. Subsequently, the engineered exosomes encapsulating miR-141-3p (miR-141-3pOE -Exos) are isolated from adipose-derived mesenchymal stem cells transfected with Lv-miR-141-3p. MiR-141-3pOE -Exos show the same inhibitive effects as miR-141-3p mimics on the pathological behaviors of HSFs in vitro. The DMNAs for sustained release of miR-141-3pOE -Exos are further fabricated in vivo. MiR-141OE -Exos@DMNAs effectively decrease the thickness of HS and improve fibroblast distribution and collagen fiber arrangement, and downregulate the expression of α-SMA, COL-1, FN, TGF-ß2, and p-Smad2/3 in the HS tissue. Overall, a promising, effective, and convenient exosome@DMNA-based miRNA delivery strategy for HS treatment is provided.

Innovative Fabrication of Hollow Microneedle Arrays Enabling Blood Sampling with a Self-Powered Microfluidic Patch.

Microneedles are gaining a lot of attention in the context of sampling cutaneous biofluids such as capillary blood. Their minimal invasiveness and user-friendliness make them a prominent substitute for venous puncture or finger-pricking. Although the latter is suitable for self-sampling, the impracticality of manual handling and the difficulty of obtaining enough qualitative sample is driving the search for better solutions. In this context, hollow microneedle arrays (HMNAs) are particularly interesting for completely integrating sample-to-answer solutions as they create a duct between the skin and the sampling device. However, the fabrication of sharp-tipped HMNAs with a high aspect ratio (AR) is challenging, especially since a length of ≥1500 µm is desired to reach the blood capillaries. In this paper, we first described a novel two-step fabrication protocol for HMNAs in stainless steel by percussion laser drilling and subsequent micro-milling. The HMNAs were then integrated into a self-powered microfluidic sampling patch, containing a capillary pump which was optimized to generate negative pressure differences up to 40.9 ± 1.8 kPa. The sampling patch was validated in vitro, showing the feasibility of sampling 40 µL of liquid. It is anticipated that our proof-of-concept is a starting point for more sophisticated all-in-one biofluid sampling and point-of-care testing systems.

Enhanced Transdermal Delivery of Acyclovir via Hydrogel Microneedle Arrays.

Hydrogel microneedles represent a promising approach to deliver drug molecules across skin into systemic circulation in a sustained release manner and without any polymer residue within skin. Acyclovir is an antiviral drug used for the treatment of several viral infections. However, the oral administration of acyclovir may cause gastrointestinal tract (GIT) disturbances with low bioavailability and poor patient compliance due to its requirement of five daily administrations to produce the desired effect. Therefore, it is thought that the preparation of hydrogel microneedle arrays containing acyclovir would improve the bioavailability and patient compliance by reducing the frequency of administration to once daily as well as overcome the GIT side effects associated with oral administration. A mixture of PEG 10,000 Da and PMVE/MA co-polymer 1,980,000 Da at a ratio of 1:3 (7.5%:22.5% w/w) with Na2CO3 3% w/w was found to produce the optimum hydrogel microneedle array formulation (F8) which showed suitable needle formation with an appropriate mechanical strength and excellent insertion ability, high drug content, sufficient swelling property and a sustained drug release over a period of 24 hours. The Ex vivo permeation study across human skin has demonstrated that the permeation of acyclovir from F8 hydrogel microneedle array was significantly (P≤ 0.05) increased by 39 times in comparison with microneedle-free film (control). The microneedle array has delivered 75.56% ± 4.2 of its loading dose over 24 hours, while the control film was only able to deliver 1.94% ± 0.14 of the total loading dose during the same period. Accordingly, these findings propose the potential application of hydrogel microneedle arrays for the transdermal delivery of acyclovir in a sustained release manner over 24 hours.

Wearable microneedle array-based sensor for transdermal monitoring of pH levels in interstitial fluid.

Microneedle-based wearable sensors offer an alternative approach to traditional invasive blood-based health monitoring and disease diagnostics techniques. Instead of blood, microneedle-based sensors target the skin interstitial fluid (ISF), in which the biomarker type and concentration profile resemble the one found in the blood. However, unlike blood, interstitial fluid does not have the same pH-buffering capacity causing deviation of pH levels from the physiological range. Information about the skin ISF pH levels can be used as a biomarker for a wide range of pathophysiological conditions and as a marker for the calibration of a wearable sensor. The ISF pH can significantly affect the detection accuracy of other biomarkers as it influences enzyme activity, aptamer affinity, and antibody-antigen interaction. Herein, we report the fabrication of a high-density polymeric microneedle array-based (PMNA) sensing patch and its optimization for the potentiometric transdermal monitoring of pH levels in ISF. The wearable sensor utilizes a polyaniline-coated PMNA having a density of ∼10,000 microneedles per cm2, containing individual microneedles with a height of ∼250 µm, and a tip diameter of ∼2 µm. To prevent interference from other body fluids like sweat, an insulating layer is deposited at the base of the PMNA. The wearable pH sensor operates from pH 4.0 to 8.6 with a sensitivity of 62.9 mV per pH unit and an accuracy of ±0.036 pH units. Furthermore, testing on a mouse demonstrates the ability of the PMNA to provide a real-time reading of the transdermal pH values. This microneedle-based system will significantly contribute to advancing transdermal wearable sensors technology, simplifying the fabrication process, and improving the cost-effectiveness of such devices.

Finite element analysis and optimization of microneedle arrays for transdermal vaccine delivery: comparison of coated and dissolving microneedles.

Microneedle arrays have recently been proposed as an alternative device for delivering vaccines into the skin. In recent years, many types of microneedles, such as coated and dissolving microneedles, have been developed with a variety of array configurations. However, the study that alongside compares the vaccine delivery efficiency of different types of microneedles and optimizes their arrangements on an array has been lacking. This study aimed to evaluate the vaccine delivery efficiency of coated and dissolving microneedles as well as to optimize the microneedle arrangements by using a three-dimensional finite element modeling approach. The constructed models describe the antigen release via diffusion, the antigen-receptor binding, and the antigen internalization by antigen-presenting cells (APCs) in the skin layers. Our modeling result reveals that the coated microneedle provides higher efficiency in activating APCs than the dissolving microneedle. It also predicts that the square arrangement of microneedles is not the optimal arrangement. According to the magnitude of APC activation, the acute-angle arrangement of microneedles outperforms the square arrangement by activating more APCs in the dermis.

3D-printed microneedle arrays for drug delivery.

Microneedle arrays provide an efficient tool for transdermal drug delivery in a minimally invasive and painless manner, showing great potential applications in medicine. However, it remains challenging to fabricate the desired microneedle arrays, because of their micron-scale size and fine structure. Novel manufacturing technologies are very wanted for the development of microneedle arrays, which would solidly advance the clinical translation of microneedle arrays. 3D printing technology is a powerful manufacturing technology with superiority in fabricating personalized and complex structures. Currently, 3D printing technology has been employed to fabricate microneedle arrays, which could push more microneedle arrays into clinic and inspire the development of future microneedle arrays. This work reviews the art of 3D printing microneedle arrays, the benefits of fabricating microneedle arrays with 3D printing, and the considerations for clinical translation of 3D-printed microneedle arrays. This work provides an overview of the current 3D-printed microneedle arrays in drug delivery.

Skin-targeted delivery of extracellular vesicle-encapsulated curcumin using dissolvable microneedle arrays.

Therapeutic benefits of curcumin for inflammatory diseases have been demonstrated. However, curcumin's potential as a clinical therapeutic has been hindered due to its low solubility and stability in vivo. We hypothesized that a hybrid curcumin carrier that incorporates albumin-binding and extracellular vesicle (EV) encapsulation could effectively address the current challenges of curcumin delivery. We further postulated that using dissolvable microneedle arrays (dMNAs) for local delivery of curcumin-albumin-EVs (CA-EVs) could effectively control skin inflammation in vivo. Mild sonication was used to encapsulate curcumin and albumin into EVs, and the resulting CA-EVs were integrated into tip-loaded dMNAs. In vitro and in vivo studies were performed to assess the stability, cellular uptake, and anti-inflammatory bioactivity of dMNA-delivered CA-EVs. Curcumin in CA-EVs exhibited at least five-fold higher stability in vitro than naïve curcumin or curcumin-EVs without albumin. Incorporating CA-EVs into dMNAs did not alter their cellular uptake or anti-inflammatory bioactivity. The dMNA embedded CA-EVs retained their bioactivity when stored at room temperature for at least 12 months. In rat and mice models, dMNA delivered CA-EVs suppressed and significantly reduced lipopolysaccharide and Imiquimod-triggered inflammation. We conclude that dMNA delivery of CA-EVs has the potential to become an effective local-delivery strategy for inflammatory skin diseases. STATEMENT OF SIGNIFICANCE: We introduce and evaluate a skin-targeted delivery system for curcumin that synergistically combines albumin association, extracellular-vesicle encapsulation, and dissolvable microneedle arrays (dMNAs) . In vitro, curcumin-albumin encapsulated extracellular vesicles (CA-EVs) inhibit and reverse the LPS-triggered expression of inflammatory transcription factor NF-κB. The integration of CA-EVs into dMNAs does not affect them physically or functionally. Importantly, dMNAs extend EV storage stability for at least 12 months at room temperature with minimal loss in their bioactivity. We demonstrate that dMNA delivered CA-EVs effectively block and reverse skin inflammation in vivo in mouse and rat models.

Multifunctional Inverse Opal Microneedle Arrays for Drug Delivery and Monitoring.

Microneedle arrays (MNs) have a demonstrated value in transdermal drug delivery systems. Attempts to this technology focus on the generation of functional MNs to achieve intelligent drug delivery. Here, multifunctional inverse opal microneedle (IOMN) arrays with the abilities are reported to load various drugs and monitor drug release. The IOMNs are generated by using poly(ethylene glycol) diacrylate (PEGDA) to replicate hierarchical structure templates that are composed of self-assembled silica colloidal nanoparticles in the inverted cone structure wells. Because of their interconnected porous structures, different actives, or drugs can be loaded into the IOMNs without organic solvents and chemical polymerization. It is demonstrated that when these drugs loaded IOMNs pierce the skin at position of interest and for slow release, the average refractive index of the IOMNs decreases with the release process, resulting in a corresponding blueshift of their characteristic spectrum. Thus, by measuring the wavelength shift value of the IOMNs, the amount of released drugs can be monitored, providing essential guidance for efficient clinical treatment. These features indicate that the IOMNs are valuable smart drug delivery systems in personalized therapy.

Biofabricating hollow microneedle array with controllable microstructure for cell transplantation.

Microneedles improve upon the direct injection method by piercing the epidermis to create microchannels for drug delivery in a painless and minimally invasive way. With these microchannels, large macromolecules can penetrate the skin barrier to reach the underlying target tissue. In this study, poly(methyl methacrylate) (PMMA) hollow microneedles (HMN) arrays were fabricated to transplant cells. The result showed that HMN arrays have good biocompatibility. Human epidermal melanocytes and follicle dermal papilla cells were shown to be successfully delivered to acellular porcine skin tissue. Similarly, human corneal keratocytes and corneal epithelial cells were shown to be successfully delivered to acellular porcine corneal tissue. The delivered cells proliferated and penetrated into the tissue. This system may have the potential in the application of cell delivery or cell transplantation.

Skin codelivery of contact sensitizers and neurokinin-1 receptor antagonists integrated in microneedle arrays suppresses allergic contact dermatitis.

BACKGROUND: Allergic contact dermatitis (CD) is a chronic inflammatory skin disease caused by type 1 biased adaptive immunity for which there is an unmet need for antigen (Ag)-specific immunotherapies. Exposure to skin sensitizers stimulates secretion of the proinflammatory neuropeptides substance P and hemokinin 1, which signal via the neurokinin-1 receptor (NK1R) to promote the innate and adaptive immune responses of CD. Accordingly, mice lacking the NK1R develop impaired CD. Nonetheless, the role and therapeutic opportunities of targeting the NK1R in CD remain to be elucidated. OBJECTIVE: We sought to develop an Ag-specific immunosuppressive approach to treat CD by skin codelivery of hapten and NK1R antagonists integrated in dissolvable microneedle arrays (MNA). METHODS: In vivo mouse models of contact hypersensitivity and ex vivo models of human skin were used to delineate the effects and mechanisms of NK1R signaling and the immunosuppressive effects of the contact sensitizer NK1R antagonist MNA in CD. RESULTS: We demonstrated in mice that CD requires NK1R signaling by substance P and hemokinin 1. Specific deletion of the NK1R in keratinocytes and dendritic cells, but not in mast cells, prevented CD. Skin codelivery of hapten or Ag MNA inhibited neuropeptide-mediated skin inflammation in mouse and human skin, promoted deletion of Ag-specific effector T cells, and increased regulatory T cells, which prevented CD onset and relapses locally and systemically in an Ag-specific manner. CONCLUSIONS: Immunoregulation by engineering localized skin neuroimmune networks can be used to treat cutaneous diseases that like CD are caused by type 1 immunity.

The Nanoparticle-Enabled Success of COVID-19 mRNA Vaccines and the Promise of Microneedle Platforms for Pandemic Vaccine Response.

The coronavirus disease 2019 (COVID-19) public health crisis has reached critical mass, but interdisciplinary research efforts have provided the global community with the first effective medical intervention to fight the pandemic-COVID-19 vaccines. Two of the vaccines approved for use in the United States and Europe deliver nucleic acid in the form of mRNA, the success of which would not be possible without biomaterials. Lipid nanoparticle (LNP)-based mRNA vaccines, discussed in this perspective, protect nucleic acids from degradation and deliver cargo directly to the intracellular compartment of cells where it is translated into the antigenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein that triggers protective immune responses. Despite success of LNP-based mRNA vaccines thus far, the pandemic has highlighted the need for emerging technologies that enable rapid development and increased accessibility to vaccination. Microneedle arrays, also discussed in this study, provide features that could lower barriers to vaccine access in resource-poor regions. The ability to exchange antigens within arrays could also facilitate swift vaccine deployment as public health needs evolve (e.g., in response to SARS-CoV-2 variants or entirely new pathogens). Therefore, the COVID-19 pandemic has spotlighted the readiness and value of biomaterials for the prevention and management of disease outbreaks.

Fast Customization of Microneedle Arrays by Static Optical Projection Lithography.

Customized microneedle arrays (CMNAs) hold great promise for precise transdermal delivery in a minimally invasive manner. Currently, the fast customization of microneedle arrays remains a great challenge. Here, we show a static optical projection lithography (SOPL) technology for fast 3D printing CMNAs. In this technology, the digital light is statically projected to induce the spatial polymerization of monomer solutions, and therefore microneedle formation can be precisely controlled by the intensity distribution of the projected light. The obtained CMNAs do not have the stair-like surface and layer-by-layer structure that are associated with the common 3D-printing technologies. This method enables fast fabrication of CMNAs with designed shape, size, and distribution in seconds without mechanical motion system. Up-conversion nanoparticles (UCNPs) were delivered into skin by the CMNAs, to form a personalized dot matrix for in vivo information storage. Under the irradiation of near-infrared (NIR) light, the UCNPs in skin displayed a visible dot matrix, presenting information encoded in the structure of CMNAs. This work demonstrates a SOPL technology for rapidly customizing high-quality microneedle arrays and a CMNA-mediated in vivo information storage strategy.

Simultaneous Delivery of Multiple Antimicrobial Agents by Biphasic Scaffolds for Effective Treatment of Wound Biofilms.

Biofilms pose a major challenge to control wound-associated infections. Due to biofilm impenetrability, traditional antimicrobial agents are often ineffective in combating biofilms. Herein, a biphasic scaffold is reported as an antimicrobial delivery system by integrating nanofiber mats with dissolvable microneedle arrays for the effective treatment of bacterial biofilms. Different combinations of antimicrobial agents, including AgNO3 , Ga(NO3 )3 , and vancomycin, are incorporated into nanofiber mats by coaxial electrospinning, which enables sustained delivery of these drugs. The antimicrobial agents-incorporated dissolvable microneedle arrays allow direct penetration of drugs into biofilms. By optimizing the administration strategies, drug combinations, and microneedle densities, biphasic scaffolds are able to eradicate both methicillin-resistant Staphylococcus aureus (MRSA) and MRSA/Pseudomonas aeruginosa blend biofilms in an ex vivo human skin wound infection model without necessitating surgical debridement. Taken together, the combinatorial system comprises of nanofiber mats and microneedle arrays can provide an efficacious delivery of multiple antimicrobial agents for the treatment of bacterial biofilms in wounds.

From the laboratory to the end-user: a primary packaging study for microneedle patches containing amoxicillin sodium.

As microneedle (MN) patches progress towards commercialisation, there is a need to address issues surrounding their translation from the laboratory to the end-user. One important aspect of MN patches moving forward is appropriate primary packaging. This research focuses on MN patches containing amoxicillin (AMX) sodium for the potential treatment of neonatal sepsis in hot and humid countries. A MN patch consists of a hydrogel-forming MN array and a drug-containing reservoir. Improper primary packaging in hot and humid countries may result in degradation of active pharmaceutical ingredients, with the use of substandard medicines a major health concern. The research presented here, for the first time, seeks to investigate the integrity of MN patches in different primary packaging when stored under accelerated storage conditions, according to international guidelines. At pre-defined intervals, the performance of the MN patch was investigated. Major causes of drug instability are moisture and temperature. To avoid unnecessary degradation, suitable primary packaging was sought. After 168 days, the percentage of AMX sodium recovered from drug-containing reservoirs packaged in Protect™ 470 foil was 103.51 ± 7.03%. However, packaged in poly(ester) foil, the AMX sodium content decreased significantly (p = 0.0286), which is likely due to the degradation of AMX sodium by the imbibed moisture. Therefore, convincing evidence was provided as to the importance of investigating the stability of MN patches in primary packaging intended for MN-mediated transdermal delivery so that they are 'fit for purpose' when it reaches the end-user. Future work will include qualitative studies to assess MN patch usability.

Microneedle Arrays Combined with Nanomedicine Approaches for Transdermal Delivery of Therapeutics.

Organic and inorganic nanoparticles (NPs) have shown promising outcomes in transdermal drug delivery. NPs can not only enhance the skin penetration of small/biomacromolecule therapeutic agents but can also impart control over drug release or target impaired tissue. Thanks to their unique optical, photothermal, and superparamagnetic features, NPs have been also utilized for the treatment of skin disorders, imaging, and biosensing applications. Despite the widespread transdermal applications of NPs, their delivery across the stratum corneum, which is the main skin barrier, has remained challenging. Microneedle array (MN) technology has recently revealed promising outcomes in the delivery of various formulations, especially NPs to deliver both hydrophilic and hydrophobic therapeutic agents. The present work reviews the advancements in the application of MNs and NPs for an effective transdermal delivery of a wide range of therapeutics in cancer chemotherapy and immunotherapy, photothermal and photodynamic therapy, peptide/protein vaccination, and the gene therapy of various diseases. In addition, this paper provides an overall insight on MNs' challenges and summarizes the recent achievements in clinical trials with future outlooks on the transdermal delivery of a wide range of nanomedicines.

Recent advances on microneedle arrays-mediated technology in cancer diagnosis and therapy.

Regarding the increasing prevalence of cancer throughout the globe, the development of novel alternatives for conventional therapies is inevitable to circumvent limitations such as low efficacy, complications, and high cost. Recently, microneedle arrays (MNs) have been introduced as a novel, minimally invasive, and low-cost approach. MNs can delivery both small molecule and macromolecular drugs or even nanoparticles (NPs) to the tumor tissue in a safe and controlled manner. Relying on the recent promising outcomes of MNs in transdermal delivery of anticancer agents, this review is aimed to summarize constituent materials, fabrication methods, advantages, and limitations of different types of MNs used in cancer therapy applications. This review paper also presents the potential use of MNs in transdermal delivery of NPs for effective chemotherapy, gene therapy, immunotherapy, photodynamic, and photothermal therapy. Additionally, MNs are currently explored as routine point-of-care health monitoring devices for transdermal detection of cancer biomarkers or physiologically relevant analytes which will be addressed in this paper. Despite the promising potential of MNs for cancer therapy and diagnosis, several limitations have impeded their therapeutic efficacy and real-time applicability that are addressed in this paper.