Microneedles Research Articles

Fabrication and mechanical/biological evaluations of dissolving bird-bill microneedle arrays.

Coated microneedles (MNs) have several disadvantages, including limited drug doses, decreased skin puncture ability due to drug coating, and a risk of clogging and infection due to repeated application. We aimed to fabricate a dissolving bird-bill MN (dBB MN) with a vertical groove between two thin plate-shaped needles and needle pedestal. Moreover, we evaluated its ability to transdermally deliver a large-molecular-weight insulin into the systemic circulation. Hydrogels with various concentrations of polyvinylpyrrolidone (PVP) or sodium hyaluronate (HA) were prepared, and dBB MN arrays were fabricated by micromolding under negative pressure for potential mass production. The needle height of the dBB MN was at the maximum when the hydrogel was 25 w/w% PVP, with a viscosity of 8-9Pa∙s. Furthermore, the buckling force of dBB MNs made from 25 w/w% PVP was 130.6 ± 51.0 mN, which increased to 195.6 ± 65.3 mN when insulin was added at 1 w/w%. The skin insertion ability of dBB MN was investigated using swain skin, with micro-holes were confirmed on the skin surface. dBB MN showed biphasic dissolution in the skin; the plate-shaped needles were immediately dissolved within 10min, while the needle pedestal was slowly dissolved over 180min. The blood glucose concentration in diabetic rats decreased slowly and significantly after a 3-h application of the insulin-loaded dBB MN array. Therefore, the dBB MN array demonstrated sufficient ability to puncture skin and transdermally deliver a large-molecular-weight drug into the systemic circulation. These findings suggest that the dBB MN array holds promise as a minimal invasive drug delivery platform, with potential applications in improving patient adherence and expanding access to essential therapies, particularly in resource-limited settings.

Advances in Research of Hydrogel Microneedle-Based Delivery Systems for Disease Treatment

Microneedles (MNs), composed of multiple micron-scale needle-like structures attached to a base, offer a minimally invasive approach for transdermal drug delivery by penetrating the stratum corneum and delivering therapeutic agents directly to the epidermis or dermis. Hydrogel microneedles (HMNs) stand out among various MN types due to their excellent biocompatibility, high drug-loading capacity, and tunable drug-release properties. This review systematically examines the matrix materials and fabrication methods of HMN systems, highlighting advancements in natural and synthetic polymers, and explores their applications in treating conditions such as wound healing, hair loss, cardiovascular diseases, and cancer. Furthermore, the potential of HMNs for disease diagnostics is discussed. The review identifies key challenges, including limited mechanical strength, drug-loading efficiency, and lack of standardization, while proposing strategies to overcome these issues. With the integration of intelligent design and enhanced control over drug dosage and safety, HMNs are poised to revolutionize transdermal drug delivery and expand their applications in personalized medicine.

Using Oscillation to Improve the Insertion Depth and Consistency of Hollow Microneedles for Transdermal Insulin Delivery with Mechanistic Insights.

Microneedles (MNs) offer the potential for discrete and painless transdermal drug delivery, yet poor insertion and dosing consistency have hindered their clinical translation. Specifically, hollow MNs are appropriate for the administration of liquid modalities, including insulin, which could prove to be beneficial for patients with type 1 diabetes mellitus. This work aimed to design and manufacture a hollow MN with an improved insertion and delivery profile suitable for insulin administration. Ex vivo insertion studies demonstrated that oscillation of MNs upon insertion into skin produced a favorable insertion profile, with reduced variation, compared to static MN insertion. Histological staining showed that this could be due to the repeated motion of the oscillating MN disrupting elastic fibers in the dermis. Additionally, permeation studies demonstrated that increased quantities of insulin were able to permeate the skin when oscillation was employed compared to static MN insertion. This study has shown that oscillation is a valuable tool in improving the transdermal delivery of insulin via a single hollow MN in vitro. Moving forward, in vivo studies should be completed to gain a fuller understanding of the benefits of the oscillation of MNs on transdermal drug delivery.

Dissolving alginate-based blend microneedles with enhanced mechanical performance for transdermal delivery of vitamin B12

Transdermal delivery of vitamin B12 (Vit-B12) is challenging due to its high hydrophilicity and molecular weight that limit permeation through the skin. Polymeric microneedles (MNs) have been demonstrated to facilitate enhanced transdermal delivery of various drugs with different properties, by piercing the outermost layer of the skin barrier in a minimally-invasive manner. Although sodium alginate (SA) has been widely investigated and used for pharmaceutical and biomedical applications, MNs made of pure SA, exhibit poor mechanical properties. Therefore, this study investigates the effect of incorporating different excipients into SA MNs, to enhance their insertion ability and mechanical performance, by a modified vacuum deposition micromolding method. Among these, poly(vinylpyrrolidone) (PVP) and polyethylene glycol (PEG)-containing SA MNs at a ratio of 1:8 show improved mechanical strength with minimal height reduction (< 10%) at all tested forces, and higher insertion capabilities into a skin-simulant parafilm model (> 65% in the second layer), compared to control SA MNs. Consequently, Vit-B12 was successfully loaded and concentrated into the MN shafts of the lead formulations, by the addition of hydroxypropyl cellulose to the baseplate. Vit-B12 MNs were characterized by means of fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) measurements, drug loading and dissolution kinetics. The MNs exhibited adequate mechanical properties and a complete drug release within 30 min, while a considerable fraction was released after few minutes. The present study shows promising findings regarding the potential use of SA in the preparation of dissolving MNs with enhanced mechanical performance for transdermal delivery of Vit-B12. However, further preclinical investigations are necessary to comprehensively evaluate their therapeutic efficacy. Additionally, this work suggests that alginate-based blend MNs may have a potential application in the delivery of other hydrophilic and large compounds for improved therapeutic outcomes.

Comparing effects of terpene-based deep eutectic solvent and solid microneedles on skin permeation of drugs with varying lipophilicity

Transdermal delivery of therapeutic molecules is often hindered by the properties of the skin, with the stratum corneum serving as the primary permeation barrier. To overcome this barrier, the integrity of the stratum corneum can be modified by chemical permeation enhancers, such as deep eutectic solvents (DESs), or by mechanically impairing the skin with microneedles (MNs). However, a systematic comparison between these strategies is currently lacking. Hence, this study examined the potential of DESs and MNs to promote the permeation and retention of drugs with varying lipophilicities – specifically, the hydrophilic drug metronidazole (logP ∼ 0), the moderately lipophilic drug lidocaine (logP ∼ 2.3), and the highly lipophilic drug clotrimazole (logP ∼ 5). A mixture of menthol and thymol was selected as a model terpene-based DES and delivery vehicle, while a DermaPen equipped with solid MNs was used to mechanically impair the skin. Permeation rates of model drugs applied to the skin with either DES, MNs, or both were compared to the rates determined for the drugs applied in control vehicles. Both strategies were found to compromise the skin barrier function, but their permeation-enhancing effect was dependent on the lipophilicity of tested model drug. The DES was most effective for the hydrophilic drug metronidazole, while the MNs were more effective in increasing the permeation of the highly lipophilic drug clotrimazole. For the moderately lipophilic drug lidocaine, neither the DES nor microneedles increased its permeation rate, as the drug permeated through the skin well on its own. Notably, the combination of both enhancement strategies did not result in significantly better permeation rates of the drugs compared to the individual approaches. In conclusion, both the terpene-based DES and solid MNs are effective strategies to enhance drug permeation through the skin, but our results suggest that the choice of strategy should be dictated by the drug’s lipophilicity. Moreover, from a permeation-enhancing perspective, there is no benefit in combining these two strategies.

Transdermal delivery of Acheta domesticus protein hydrolysate using nanostructured lipid carriers and Derma Stamp ― Does the combination of lipid-based formulation and a physical technique add value for permeation and retention?

Acheta domesticus protein hydrolysate (PH) is a natural anti-skin aging compound, but its effectiveness is hindered by poor skin penetration due to its hydrophilicity and high molecular weight. This study aimed to compare the enhancement of PH skin delivery by increasing lipophilicity with nanostructured lipid carriers (NLCs) and bypassing the skin barrier using physical techniques, including Derma Stamp and dissolving microneedles (MNs). Fluorescein isothiocyanate (FITC)-tagged PH was prepared to track the transdermal transport, and complexed with dioctyl sodium sulfosuccinate (DSS) to be encapsulated into NLCs, prepared using a melt emulsification method. Skin delivery was evaluated in terms of skin permeation and skin retention using Franz diffusion cells. The FITC-PH loaded NLCs had a particle size of 238.9 ± 0.8 nm, a polydispersity index of 0.3 ± 0.0, a zeta potential of −23.6 ± 1.0 mV, and an encapsulation efficiency of 65.1 ± 2.1%. The MNs, prepared with polyvinylpyrrolidone K30 and polyvinyl alcohol (38:15 weight ratio), had uniform sharp needles and a high FITC-PH loading capacity of 97.2 ± 1.9%. PH permeation was most effectively enhanced through physical barrier bypassing, particularly with the Derma Stamp, followed by MNs and finally due to incorporation into NLCs. Notably, when utilizing the Derma Stamp, converting the aqueous solution of PH into an NLC formulation added positive benefits by significantly improving skin retention. In conclusion, it was suggested that while physical enhancement methods are crucial for permeation of the PH, optimizing formulation characteristics, such as incorporation into NLCs, further increased the overall effectiveness of skin delivery.

Self-healing hydrogels loaded with Spatholobi Caulis alleviate disc degeneration by promoting autophagy in nucelus pulposus

Intervertebral disc degeneration (IDD) is a common degenerative disease of the spine that has a significant impact on both society and human health. Many studies have confirmed that there is a close relationship between IDD and senescence and apoptosis, and autophagy can combat apoptosis and senescence. Spatholobi caulis (SC) is an herb that contains various active compounds that are effective in tissue repair and regeneration, but it has not been explored in field of IDD. In this study, it was first found that SC can boost autophagy and reduce the apoptosis and senescence of Nucleus pulposus cell (NPCs). However, our animal studies revealed limited absorption of SC. To improve the bioavailability and efficacy of SC, we developed a hydrogel incorporating quaternary ammonium chitosan (QCS) and oxidized starch (OST) as carriers for SC. The QCS-OST/SC hydrogel exhibits excellent compatibility with cells, can be easily injected, and can release SC durably. At the cellular level, the QCS-OST/SC hydrogel enhances cell viability, initiates autophagy and release of the extracellular matrix (ECM), and inhibits cellular senescence and apoptosis. The injection of the QCS-OST/SC hydrogel via microneedles (MNs) into discs had successfully diminished disc degeneration in rats, which shows that this hydrogel has broad potential in the treatment of IDD.

Design, fabrication, and evaluation of antimicrobial sponge microneedles for the transdermal delivery of insulin

Transdermal drug delivery systems hold promise, but their effectiveness is often constrained by the skin’s barrier. Microneedles (MNs) improve drug permeability by creating micro-channels in the skin, yet they continue to face challenges such as infection risks and safety concerns. To overcome these challenges, a novel antimicrobial sponge MNs (ASMNs@PVP-INS) modified with polyvinylpyrrolidone (PVP) for insulin (INS) delivery was designed. Mechanical testing demonstrated that these MNs possess excellent mechanical strength, capable of withstanding at least 0.11 N per needle without rupture. In vitro drug penetration tests revealed that the MNs consistently released over 75 % of INS within a 6 h. In an animal model, ASMNs@PVP-INS reduced initial blood glucose levels from 22.4 to 5.72 mmol/L, effectively maintaining glucose control for more than 6 h without inducing hypoglycemia. Additionally, agar diffusion assays indicated that INS loading did not compromise the antimicrobial properties of antimicrobial sponge MNs (ASMNs). Skin irritation tests showed that ASMNs@PVP-INS exhibited mild irritation (PII < 0.6), with skin damage fully recovering within 8 h. Safety assessments indicated no significant toxicity to mice, with biochemical markers remaining within normal ranges, thereby confirming their good biocompatibility. In conclusion, ASMNs@PVP-INS hold promise as a novel drug delivery vehicle.

A development of a gelatin and sodium carboxymethyl cellulose hydrogel system for dual-release transdermal delivery of lidocaine hydrochloride

This study introduces a dual-release transdermal drug delivery system using a hydrogel matrix of cross-linked gelatin and sodium carboxymethyl cellulose (NaCMC). Designed for immediate drug release from microneedles (MNs) and sustained release from microcapsules (MCs), this system utilizes lidocaine hydrochloride as the model drug. The fabrication process involved casting the hydrogel into MN molds, with MCs embedded in the backing layer, establishing a dual-release mechanism. MCs of gelatin and NaCMC were prepared by emulsion-crosslinking method and using glutaraldehyde as a crosslinker. MCs ranged in size from 50 to 264 μm and exhibited the highest drug release in acidic environments, showcasing a pH-responsive nature. Drug loading efficiency reached 9.8 %, while encapsulation efficiency was 75.8 %. The MNs, which had a conical shape and strong mechanical properties, demonstrated excellent penetration capabilities. The in vitro release profile indicated an initial burst within 10 min, followed by sustained release over 240 min, in line with the Korsmeyer-Peppas model. Additionally, the system displayed significant antimicrobial properties and good biocompatibility, with cell viability exceeding 86 %. This confirms its potential as a safe and effective platform for transdermal drug delivery.

A hyaluronic acid-based dual-functional hydrogel microneedle system for sequential melanoma ablation and skin regeneration

Melanoma treatment remains a challenge due to the inadequacy of existing clinical approaches and the difficulty of tissue regeneration. Recently, microneedles have been widely studied in tumor therapy and skin repair. Hence, a hyaluronic acid (HA)-based dual-functional hydrogel microneedle (MN) system was constructed to sequentially achieve tumor ablation and skin regeneration. Carbon nanotubes@calcium peroxide@tannic acid-Fe/chlorin e6 (CCa@TF/Ce6) nanomaterial was encapsulated in dissolvable polyvinyl alcohol/polyvinylpyrrolidone tips and accurately released to the tumor site to suppress melanoma via the photothermal and photodynamic therapies under the dual laser irradiation due to the generation of reactive oxygen species (ROS) and heat. Particularly, ROS and heat triggered immunogenic cell death, promoted dendritic cells maturation and reshaped the tumor-associated macrophage phenotype from the protumor M2 phenotype to the anti-tumor M1 phenotype, ultimately activating autoimmunity to eliminate the tumor. Following tumor ablation, the MN base accelerated skin regeneration owing to HB-PVA hydrogel through reducing oxidative stress, promoting cell proliferation and facilitating cell migration. Overall, the dual-functional hydrogel MN designed in this study, offers a new avenue for sequential melanoma combination treatment and skin regeneration.

Microneedles Constructed by Swellable Hydrogels Loaded with Celastrol for Efficient Treatment of Skin Infections Induced by Drug-Resistant Bacterial Strains.

The urgent need for new antimicrobial drugs arises from the limited efficacy of traditional antibiotics against emerging drug-resistant strains. Celastrol (CSL) demonstrates an exceptional antibacterial property that remains unaffected by bacterial resistance, but its poor water solubility limits its wide applications. This study uses the hydrophobic inner cavity of mono-(6-diethylenetriamine-6-deoxy)-β-cyclodextrin (mβ-CD) (a derivative of cyclodextrin) to encapsulate CSL, constructing an inclusion complex (CSL@mβ-CD) to enhance the water solubility of CSL. The obtained inclusion complex is further incorporated into a swellable hydrogel microneedle (MN) to obtain CSL@mβ-CD/MN. The fabricated CSL@mβ-CD/MN can enable the sustained release of CSL, achieving effective bacterial eradication at infected sites. In vivo experiments demonstrate that CSL@mβ-CD/MN has a remarkable efficacy in the treatment of methicillin-resistant Staphylococcus aureus-induced subcutaneous abscesses and wound infections. Specifically, CSL@mβ-CD/MN can effectively penetrate the stratum corneum of the skin to realize rapid elimination of the bacteria in wounds. Moreover, CSL@mβ-CD/MN can efficiently scavenge reactive oxygen species, promote M2 polarization of macrophages, and relieve local inflammation at the wound sites. These results reveal that CSL@mβ-CD/MN holds great promise in the clinical treatment of acute skin infections induced by drug-resistant bacteria.

Self-Extracting Dextran-Based Hydrogel Microneedle Arrays with an Interpenetrating Bioelectroenzymatic Sensor for Transdermal Monitoring with Matrix Protection.

Continuous glucose monitors have revolutionized diabetes management, yet such devices are limited by their cost, invasiveness, and stability. Microneedle (MN) arrays could offer improved comfort compared to invasive implanted or mm-sized needle devices, but such arrays are hampered by complex fabrication processes, limited mechanical and sensor stability, and/or cytotoxicity concerns. This work demonstrates the first crosslinked hydrogel microneedle-bioelectroenzymatic sensor arrays capable of biomarker extraction and robust transdermal continuous monitoring in artificial interstitial fluid for 10 days. The fabrication process via micromolding of dextran-methacrylate (Dex-MA) and dry-state visible light crosslinking is simple and permits the robust fixation of diverse prefabricated electrodes in a single array. Dry-state crosslinking minimized material shrinkage to enable the formation of resistant Dex-MA microneedles with shape control and reproducibility. The polymer substitution level (9-62%) and mass content (10-30wt%) affect the mechanical, swelling, and bioelectrocatalytic properties of the integrated sensors. Crosslinked Dex-MA hydrogel matrices provide beneficial cytotoxicity protection and flux-limiting membrane properties to the integrated second generation dehydrogenase-based nanostructured buckypaper biosensor and Ag/AgCl reference electrodes. Polysaccharide-based microneedle technology with encapsulated porous bioelectrodes promise to be a valuable alternative to more invasive devices for safer and longer-term biomarker monitoring.

A systematic review of microneedles technology in drug delivery through a bibliometric and patent overview

The transdermal drug delivery (TDD) route has gathered considerable attention for its potential to improve therapeutic efficacy while minimizing systemic side effects. Among transdermal technologies, microneedle (MN) devices have proven to be a promising approach that combines the advantages of traditional needle injections and non-invasive topical applications. This review provides a comprehensive analysis of progress in transdermal drug delivery systems (TDDS) via MN from 2000 to 2023, integrating bibliometric analysis and patent landscape to present a multi-faceted perspective on the evolution of this technology. The study identifies key trends, challenges, and opportunities in the research, implementation, and commercialization of MN tools through a systematic examination of scientific literature and an extensive investigation of global patent databases. The study of bibliometric trends reveals the leading experts, organizations, companies, and countries contributing to this field, collaboration networks, and the thematic evolution of research topics. The patent analysis offers insights into innovative trajectories, key players, and geographical distribution of intellectual property. This review resumes the latest advancements in MN devices and provides a strategic outlook that can guide future research directions, promote partnerships, and inform stakeholders involved in the development of TDDS.

Ultrasound-Responsive Carbon Monoxide Microneedle for Enhanced Healing of Infected Diabetic Wounds.

Efficient management of difficult-to-heal diabetic wounds remains a clinical challenge owing to bacterial infections, as well as oxidative and hyperglycemic complex pathology. Therefore, developing intelligent strategies for diabetic wound healing is urgently needed. Herein, an ultrasound (US)-responsive microneedle (MN) patch (MN@GOX@TiO2-X@CO) capable of controlled delivery of carbon monoxide (CO) gas within the skin for effective treatment of diabetic infected wounds is developed. Benefiting from the specific form of microneedle (MN) patch, sonosensitizer (TiO2-X), •OH-responsive CO prodrug (MPA-CO), and glucose oxidase (GOX) can be loaded together and effectively delivered to infectious wounds. With the semi-fluidic hyaluronic acid (HA) coating under the physiological condition, CO could be released efficiently in situ and directly acted on infected wound tissue upon US triggering. Both in vitro and in vivo results showed that US-triggered CO release from MN@GOX@TiO2-X@CO not only effectively inhibited the S. aureus and MRSA infection but also promoted fibroblasts proliferation and migration under hyperglycemic physiology, thereby accelerating diabetic wound healing. Collectively, the approach effectively addresses the impaired skin regeneration function in diabetic wounds and offers a promising therapeutic strategy for the efficient healing of infected diabetic wounds.

Mechanical Characterization of Individual Needles in Microneedle Arrays: Factors Affecting Compression Test Results.

Background: This study aims to investigate the impact of test conditions on the results of the compression testing of microneedle arrays (MNAs). Methods: Uniaxial compression tests were conducted on polyglycolic acid-fabricated biodegradable MNAs. Load-displacement curves were obtained for varying conditions, including the number of microneedles (MNs) compressed simultaneously, compression speeds, and compression angles. Subsequently, the buckling load and stiffness were calculated, and the MN deformation during compression was observed. Results: The buckling load and stiffness per MN decreased significantly with a simultaneous increase in compressed MNs. The mean buckling load and stiffness of 52 MNs in single-needle compression tests were 0.211 ± 0.008 N and 13.9 ± 1.3 N/mm, respectively, with no variation among the three MNAs. However, a significant difference in buckling load and stiffness was observed among the MNs within the MNAs. Additionally, buckling loads and stiffnesses were significantly lower in certain MNs at the same location in different MNAs. Buckling load and stiffness decreased significantly during inclined compression compared to during vertical compression. While the tests evaluate the mechanical properties of MNAs, test results may vary depending on test conditions. Conclusions: Compression testing of the individual MNs comprising an MNA helps evaluate the mechanical properties of MNs and ensure the quality of MNAs.

Evaluation of physical and chemical modifications to drug reservoirs for stimuli-responsive microneedles.

Hydrogel-forming microneedle (MN) arrays are minimally-invasive devices that can penetrate the stratum corneum, the main barrier to topical drug application, without causing pain. However, drug delivery using hydrogel-forming MN arrays tends to be relatively slow compared to rapid drug delivery using conventional needles and syringes. Therefore, in this work, for the first time, different physical and chemical delivery enhancement methods were employed in combination with PVA-based hydrogel-forming MN arrays. Using a model drug, ibuprofen (IBU) sodium, the designed systems were assessed in terms of the extent of transdermal delivery. Iontophoresis (ITP) and heat-assisted drug delivery technology were investigated as physical permeation enhancement techniques. Ex vivo studies demonstrated that the ITP (0.5mA/cm2)-mediated combination strategy significantly enhanced the transdermal permeation of IBU sodium over the first 6h (~ 5.11mg) when compared to MN alone (~ 1.63mg) (p < 0.05). In contrast, heat-assisted technology showed almost no promoting effect on transdermal delivery. Furthermore, IBU sodium-containing rapidly dissolving lyophilised and effervescent reservoirs, classified as chemical modification methods, were prepared. Both strategies achieved rapid and effective ex vivo IBU sodium permeation, equating to ~ 78% (30.66mg) and ~ 71% (28.43mg) from lyophilised and effervescent reservoirs, respectively. Moreover, in vivo pharmacokinetic studies showed that the IBU sodium plasma concentration within lyophilised and effervescent groups reached a maximum concentration (Cmax) at 4h (~ 282.15µg/mL) and 6h (~ 140.81µg/mL), respectively. These strategies not only provided rapid achievement of therapeutic levels (10-15µg/ml), but also resulted in sustained release of IBU sodium for at least 48h, which could effectively reduce the frequency of administration, thereby improving patient compliance and reducing side effects of IBU sodium.

Transdermal delivery of PeptiCRAd cancer vaccine using microneedle patches

Microneedles (MNs) are a prospective system in cancer immunotherapy to overcome barriers regarding proper antigen delivery and presentation. This study aims at identifying the potential of MNs for the delivery of Peptide-coated Conditionally Replicating Adenoviruses (PeptiCRAd), whereby peptides enhance the immunogenic properties of adenoviruses presenting tumor associated antigens. The combination of PeptiCRAd with MNs containing polyvinylpyrrolidone and sucrose was tested for the preservation of structure, induction of immune response, and tumor eradication. The findings indicated that MN-delivered PeptiCRAd was effective in peptide presentation in vivo, leading to complete tumor rejection when mice were pre-vaccinated. A rise in the cDC1 population in the lymph nodes of the MN treated mice led to an increase in the effector memory T cells in the body. Thus, the results of this study demonstrate that the combination of MN technology with PeptiCRAd may provide a safer, more tolerable, and efficient approach to cancer immunotherapy, potentially translatable to other therapeutic applications.

Ultrasonication-Induced Preparation of High-Mechanical-Strength Microneedles Using Stable Silk Fibroin.

Silk fibroin (SF) is an ideal material for microneedle (MN) preparation. However, long extraction and short storage durations limit its application. Furthermore, MNs prepared from SF alone are easy to break during skin insertion. In this study, a regenerated SF solution was autoclaved and freeze-dried to produce a stable and water-soluble SF sponge. The freeze-dried SF (FD-SF) solution was ultrasonically treated before being used in the fabrication of MNs. The ultrasonically modified SFMNs (US-SFMNs) were evaluated in comparison to FD-SFMNs made from FD-SF and conventional SFMNs made from regenerated SF. The results indicated that the FD-SF could be completely dissolved in water and remained stable even after 8 months of storage. FTIR and XRD analyses showed that SF in US-SFMNs had increased β-sheet content and crystallization compared to FD-SFMNs, by 7.3% and 8.1%, respectively. The US-SFMNs had higher mechanical strength than conventional SFMNs and FD-SFMNs, with a fracture force of 1.55 N per needle and a rat skin insertion depth of 370 μm. The US-SFMNs also demonstrated enhanced transdermal drug delivery and enzymatic degradation in vitro. In conclusion, the autoclaving and freeze drying of SF, as well as ultrasonication-induced MN preparation, provide promising SF-based microneedles for transdermal drug delivery.

Double-Layered Microneedle Patch Integrated with Multifunctional Nanoparticles and Live Bacteria for Long-Term Treatment of Atopic Dermatitis.

Atopic dermatitis (AD) is a complex and prevalent chronic inflammatory skin disease that impacts a significant portion of the global population. Conventional treatments often focus on a singular pathogenic factor or suffer from limited skin penetration, resulting in unsatisfactory outcomes. Here, a multifunctional double-layered microneedle (MN) patch is proposed for long-term and effective treatment of AD by integrating therapeutic nanoparticles (NPs) and live bacteria. In the design, the MN tips are loaded with Prussian blue NPs encapsulating cetirizine hydrochloride (CET@PB NPs), while the patch backing incorporates Bacillus subtilis (B. subtilis). Upon skin insertion, the MN patch efficiently delivers CET@PB NPs into the skin and deposits live B. subtilis on the skin surface after fast dissolution. The delivered NPs not only scavenge reactive oxygen species (ROS) and improve oxidative stress microenvironments in the AD lesions, but also provide sustained release of the antihistamine CET in the skin for alleviating AD symptoms. Furthermore, B. subtilis survives on the skin for over 9 days and effectively inhibits the growth of the harmful bacteria Staphylococcus aureus. These features highlight the superior efficacy of the MN patch in long-term treatment of AD, offering a promising alternative for the management of skin disorders in clinics.

Advances in Transdermal Drug Delivery: The Development of Microneedle Technology for Improved Therapeutic Outcomes

Transdermal Drug Delivery Systems (TDDS) represent a significant advancement in therapeutic administration by allowing drugs to bypass the gastrointestinal system and first-pass hepatic metabolism, enhancing patient compliance, and enabling sustained drug release. However, traditional TDDS face limitations, including resistance from the skin's natural barrier and limited efficacy in delivering large or hydrophilic molecules. Microneedle (MN) technology offers a breakthrough solution, using minimally invasive micron-sized needles to bypass the stratum corneum, facilitating efficient drug delivery without significant pain or discomfort. This review explores the evolution and recent advancements in microneedle technology, highlighting its role in overcoming the limitations of conventional TDDS. Microneedles have been shown to enhance drug bioavailability, reduce side effects, and expand the range of deliverable therapeutics, including vaccines, insulin, and genetic materials. The development of bioinspired 4D microneedles further extends their application to diagnostics and cosmetic treatments, positioning MNs as a versatile tool in modern medicine. Key sections of the review focus on the types of microneedles—solid, coated, dissolving, hollow, and hydrogel-forming—and their respective fabrication methods, materials, and drug delivery mechanisms. The review also discusses the challenges related to scaling up production, ensuring consistent quality, and regulatory hurdles in achieving clinical approval. Future directions include the integration of microneedles with nanotechnology, combination therapies, and sustainable design, particularly in developing regions where biodegradable materials may address environmental and disposal concerns. The potential for microneedle technology to revolutionize transdermal drug delivery, diagnostics, and therapeutic monitoring is significant, with ongoing research paving the way for multifunctional applications that can reshape patient care and treatment modalities.