Dissolving Microneedles Research Articles

Dissolvable hybrid microneedle patch for efficient delivery of curcumin to reduce intraocular inflammation

Intraocular inflammation seriously impairs vision, and the effectiveness of intraocular drug delivery is hampered by various physiological barriers, such as the corneal barrier. In this paper, we present a simple approach to fabricating a dissolvable hybrid microneedles (MNs) patch for the efficient delivery of curcumin to treat intraocular inflammatory disorders. Water-insoluble curcumin was first encapsulated into polymeric micelles with high anti-inflammatory capacities, and then were combined with hyaluronic acid (HA) to create a dissolvable hybrid MNs patch using a simple micromolding method. Curcumin was amorphously dispersed within the MNs patch as indicated by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and X-ray diffraction (XRD) analyses. According to an in vitro drug release study, the proposed MNs patch provided sustainable drug release over 8 h. Following its in vivo topical application, the MNs patch demonstrated an extended pre-corneal retention time over 3.5 h and exhibited great ocular biocompatibility. Additionally, such MNs patch could reversibly penetrate the corneal epithelium, generating an array of microchannels on the corneal surface, thereby increasing ocular bioavailability. Of greater significance, the use of MNs patch demonstrated the improved therapeutic effectiveness in treating endotoxin-induced uveitis (EIU) in a rabbit model compared to curcumin eye drops via a significant reduction in the infiltration of inflammatory cells such as CD45+ leukocytes and CD68+ macrophages. Overall, the topical application of the MNs patch as an efficient ocular drug delivery system could potentially serve as a promising approach for treating different types of intraocular disorders.

Sublingual Dissolving Microneedle (SLDMN)-Based Vaccine for Inducing Mucosal Immunity against SARS-CoV-2.

The coronavirus pandemic has accelerated the development of next-generation vaccination technology to combat future pandemic outbreaks. Mucosal vaccination effectively protects the mucosal surfaces, the primary sites of viral entry, by inducing the secretion of immunoglobulin A (IgA) and humoral IgG. Here, a dissolving microneedle (DMN) is adopted as a mucosal vaccine delivery platform to directly penetrate the sublingual site, which is rich in antigen-presenting cells (APCs) and lymphoid tissues. The sublingual dissolving microneedle (SLDMN) vaccination platform comprised a micropillar-based compartment and a 3D-printed SLDMN applicator as a substitute for the DMN patch. The penetration efficacy of SLDMNs is assessed using in vitro optical coherence tomography (OCT) and in vivo histological analysis. The efficacy of SLDMN is also evaluated in a vaccine form using the recombinant spike (S1) protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Furthermore, SLDMN is used to challenge transgenic mice expressing human angiotensin-converting enzyme 2 (hACE2) receptors. Its effects are evaluated on antibody production, survival rate, and inflammation attenuation after infection compared to the intramuscular (IM) injections. Overall, SLDMN effectively induced mucosal immunity via IgA secretion, attenuated lung inflammation, and lowered the levels of cytokines and chemokines, which may prevent the "cytokine storm" after SARS-CoV-2 infection.

Technical evaluation of precisely manufacturing customized microneedle array patches via inkjet drug printing

Dissolvable microneedle array patches offer the possibility to deliver active pharmaceutical ingredients bypassing the gastrointestinal tract by piercing the stratum corneum. Usually, microneedles are produced by micromolding but this often results in a waste of active pharmaceutical ingredient. In this study, inkjet printing was investigated as a manufacturing technology for dissolvable microneedle array patches. A suitable ink for the printing process was developed for lisinopril as a peptidomimetic model drug. The printing process was optimized. Povidone was found to be a promising polymer for the precise and smooth production of dissolvable microneedles. Different patterns of microneedles and blank spaces were successfully printed into one microneedle array patch. It was possible to exactly define the cavities to be filled. The amount of lisinopril was precisely adjusted between 95.14 and 99.26 % of the target dose. The applied method demonstrated the precise dosage opportunities of the inkjet printing methodology for customization and drug waste reduction. Inkjet printing could be used as a precise manufacturing method for personalized microneedle array patches as well as to combine incompatible drug substances in a single patch.

Transdermal Delivery of Estradiol Simultaneously Possessing Rapid Release and Sustained Release Effect.

Dissolving microneedle (DMN) has been researched as a drug delivery technology that improves drug molecule transportation through the skin with little discomfort. However, the sluggish drug absorption, poor skin dissolution, and lengthy time lags of DMN have limited its potential uses. The aim of this study was to design a novel DMN system for the administration of the poorly water-soluble drug, estradiol (E2), with fast skin penetration and a stable release rate for a long time. DMN containing E2 emulsion (E2-EM-DMN) and traditional DMN (T-DMN) were prepared. Rat skin was used for penetration test and guinea pig skin was used for skin irritation experiment. The drug release profiles and stability properties of these two kinds of DMNs were also investigated. High performance liquid chromatography was employed to determine the E2 content in DMN. The E2 concentration in rat plasma was achieved by a newly developed liquid chromatography-mass spectrometry method that was fast, reproducible, and specific. The height of E2-EM-DMN and T-DMN was 600μm. The drug loading of the E2-EM-DMN and T-DMN was 667.30 ± 7.21μg/patch and 672.56 ± 6.98μg/patch. E2-EM-DMN possessed enough mechanical strength to penetrate the skin and caused no irritation to the skin. E2-EM-DMN could release the drug more rapidly and more continuously than T-DMN. E2-EM-DMN had good pharmaceutical stability. In summary, the E2-EM-DMN showed reliable quality and superior release performance. Emulsion-embedded DMN is an ideal transdermal delivery system for drugs.

Biodegradable and dissolvable resveratrol nanocrystals non-silicon microneedles for transdermal drug delivery

The prevalence and lethality of cutaneous melanoma have increased in recent years. Lower skin penetration rates and poor soluble affect the effective delivery of resveratrol. To overcome these two issues, a biodegradable and dissolvable resveratrol nanocrystals non-silicon microneedles was designed in this study. The nanocrystals technology was used to improve the resveratrol solubility. Transmission electron microscopy and scanning electron microscopy demonstrated that the amorphous resveratrol nanocrystals were successfully prepared with a particle size of 161 ± 9 nm and presented a superior performance in vitro dissolution of 84.14 ± 2.53% for 120 min. For the skin permeability issue, a dissolvable microneedle, made with a biocompatible and biodegradable polymer (a mixture of polyvinylpyrrolidone and polyvinyl alcohol), exhibited exceptional mechanical strength even the microneedles matrix was loaded with the drug for 1.26 N/needle. The z-axis scanning also exhibited the uniformity of rhodamine B within the needle. And it presented rapid resveratrol releases after puncture into the mice's skin. The dissolvable microneedles loaded with the resveratrol nanocrystals provided an efficient and convenient transdermal delivery system.

Development of probiotic loaded multilayer microcapsules incorporated into dissolving microneedles for potential improvement treatment of vulvovaginal candidiasis: A proof of concept study

Vulvovaginal candidiasis (VVC) is a vaginal infection caused by abnormal growth of Candida sp., especially Candida albicans, in the vaginal mucosa. A shift in vaginal microbiota is prominent in VVC. The presence of Lactobacillus plays a vital role in maintaining vaginal health. However, several studies have reported resistance of Candida sp. against azoles drugs, which is recommended as VVC treatment. The use of L. plantarum as a probiotic would be an alternative to treat VVC. In order to exert their therapeutic activity, the probiotics needed to remain viable. Multilayer double emulsion was formulated to obtain L. plantarum loaded microcapsules (MCs), thus improving its viability. Furthermore, a vaginal drug delivery system using dissolving microneedles (DMNs) for VVC treatment was developed for the first time. These DMNs showed sufficient mechanical and insertion properties, dissolved rapidly upon insertion, facilitating probiotic release. All formulations proved non-irritating, non-toxic, and safe to apply on the vaginal mucosa. Essentially, the DMNs could inhibit the growth of Candida albicans up to 3-fold than hydrogel and patch dosage forms in ex vivo infection model. Therefore, this study successfully developed the formulation of L. plantarum-loaded MCs with multilayer double emulsion and its combination in DMNs for vaginal delivery to treat VVC.

Lidocaine-loaded dissolving microneedle for safe local anesthesia on oral mucosa for dental procedure

ABSTRACT Background Lidocaine has been widely used as a short-acting local anesthetic agent to reduce the pain caused by needle insertion. Dissolving microneedles (DMNs), which are minimally invasive, can effectively deliver drugs by overcoming the oral mucosal barrier and relieving patient discomfort. Methods Lidocaine solution prepared by mixing lidocaine-HCl and hyaluronic acid was used to fabricate oral lidocaine HCl-encapsulated DMNs (oral Li-DMNs) via centrifugal lithography. The dissolution, penetration ability, and local transmucosal drug delivery of oral Li-DMNs into the oral mucosa were evaluated in porcine jaws. Pharmacokinetic analysis and safety assessment were performed using rabbits. Results The insertion depth of the oral Li-DMNs satisfies the safety standard. The oral Li-DMNs were completely dissolved after 3 min of application. The local transmucosal drug delivery, pharmacokinetic, and safety evaluations showed that the oral Li-DMNs can obtain a local anesthesia effect at a relatively lower dose, and there was no oral mucosal irritation in rabbits. Conclusions A novel and safe oral Li-DMNs have potential applications in large animals and clinical trials and would possibly enter the anesthesia market.

Efficacy and Safety of Detachable Microneedle Patch Containing Triamcinolone Acetonide in the Treatment of Inflammatory Acne.

Detachable microneedles (DMNs) are dissolvable microneedles that detach from the base during administration. The use of DMNs-containing steroids for acne has never been investigated. Thirty-five patients with facial inflammatory acne were evaluated for acne treatment efficacy and safety of DMNs and DMNs containing triamcinolone acetonide (TA) via a 28-day randomized, double-blind, controlled trial. Four inflammatory acne lesions were selected from each participant and randomly treated with a single application of 700 µm DMNs containing 262.02 ± 15.62 µg TA (700DMNTA), 1000 µm DMNs containing 160.00 ± 34.92 µg TA (1000DMNTA), 700 µm DMN without TA (700DMN), and a control. Efficacy was measured by assessing physical grading, diameter, volume, erythema index, and melanin index. Safety was evaluated by assessing reports of adverse effects from patients and physicians. All three treatment groups achieved resolution of inflammatory acne significantly faster than the control group, with median times for resolution of 4.6, 5.25, 6.7, and 8.1 days in the 1000DMNTA, 700DMNTA, 700DMN, and control, respectively. When compared to the control group, the diameters and post-acne erythema of inflammatory acne were significantly reduced in the treatment groups. The 1000DMNTA decreased acne size and erythema more than other treatments. DMNTA also tended to decrease acne size and erythema more than DMN with no TA, but there was no statistically significant difference. All participants preferred DMN over conventional intralesional steroid injection due to less pain and self-application. No adverse effect was observed. DMNTA is a safe, effective alternative treatment for inflammatory acne and significantly reduces post-acne erythema.

Transscleral Delivery of Dexamethasone-Loaded Microparticles Using a Dissolving Microneedle Array.

Microneedles (MNs) have attracted considerable interest as a means of ocular drug delivery, a challenging delivery route due to the limitations imposed by the various biological barriers associated with this organ. In this study, a novel ocular drug delivery system was developed by formulating a dissolvable MN array containing dexamethasone-loaded PLGA microparticles for scleral drug deposition. The microparticles serve as a drug reservoir for controlled transscleral delivery. The MNs displayed sufficient mechanical strength to penetrate the porcine sclera. Dexamethasone (Dex) scleral permeation was significantly higher than in topically instilled dosage forms. The MN system was able to distribute the drug through the ocular globe, with 19.2% of the administered Dex detected in the vitreous humour. Additionally, images of the sectioned sclera confirmed the diffusion of fluorescent-labelled microparticles within the scleral matrix. The system therefore represents a potential approach for minimally invasive Dex delivery to the posterior of the eye, which lends itself to self-administration and hence high patient convenience.

Sweat induction using Pilocarpine microneedle patches for sweat testing in healthy adults

BackgroundThe sweat test using pilocarpine iontophoresis remains the gold standard for diagnosing cystic fibrosis, but access and reliability are limited by specialized equipment and insufficient sweat volume collected from infants and young children. These shortcomings lead to delayed diagnosis, limited point-of-care applications, and inadequate monitoring capabilities. MethodsWe created a skin patch with dissolvable microneedles (MNs) containing pilocarpine that eliminates the equipment and complexity of iontophoresis. Upon pressing the patch to skin, the MNs dissolve in skin to release pilocarpine for sweat induction. We conducted a non-randomized pilot trial among healthy adults (clinicaltrials.gov, NCT04732195) with pilocarpine and placebo MN patches on one forearm and iontophoresis on the other forearm, followed by sweat collection using Macroduct collectors. Sweat output and sweat chloride concentration were measured. Subjects were monitored for discomfort and skin erythema. ResultsFifty paired sweat tests were conducted in 16 male and 34 female healthy adults. MN patches delivered similar amounts of pilocarpine into skin (1.1 ± 0.4 mg) and induced equivalent sweat output (41.2 ± 25.0 mg) compared to iontophoresis (1.2 ± 0.7 mg and 43.8 ± 32.3 mg respectively). Subjects tolerated the procedure well, with little or no pain, and only mild transient erythema. Sweat chloride concentration measurements in sweat induced by MN patches (31.2 ± 13.4 mmol/L) were higher compared to iontophoresis (24.0 ± 13.2 mmol/L). Possible physiological, methodological, and artifactual causes of this difference are discussed. ConclusionsPilocarpine MN patches present a promising alternative to iontophoresis to enable increased access to sweat testing for in-clinic and point-of-care applications.

Dissolving Microneedles Loaded with Gestodene: Fabrication and Characterization In Vitro and In Vivo.

Gestodene (GEST) is widely used in female contraception. It is currently being used as an oral contraceptive. However, unfortunately, oral contraceptives are often associated with several bothersome side effects and poor compliance. Therefore, a sustained delivery system for GEST to overcome these shortcomings is highly desirable. The present study successfully developed a kind of novel dissolving microneedles (DMNs) with a potential for sustained release and a minimally invasive intradermal treatment of GEST. The dissolving microneedles containing GEST were fabricated using polyvinylpyrrolidone as the base material. The characteristics in vitro and pharmacokinetics in vivo of GEST-loaded DMNs were investigated. The results showed that the microneedle could pierce the porcine skin and release the drug at an average dose of 20µg/cm2 daily for seven days. The pharmacokinetic experiment of the microneedles indicated that the plasma level of GEST in rats increased with increasing drug dosage, and the plasma drug concentration-time curves were much flatter compared with subcutaneous injection and oral administration. In addition, no cutaneous irritation was observed. GEST-loaded DMNs may be a promising intradermal sustained delivery system for contraceptive use.

Mechanically Robust Dissolving Microneedles Made of Supramolecular Photosensitizers for Effective Photodynamic Bacterial Biofilm Elimination

Bacterial biofilms pose severe threats to public health worldwide and are intractable by conventional antibiotic treatment. Antimicrobial photodynamic therapy (PDT) is emerging as a promising strategy for eradicating biofilms by virtue of low invasiveness, broad-spectrum antibacterial activity, and nondrug resistance. However, its practical efficacy is impeded by the low water solubility, severe aggregation, and poor penetration of photosensitizers (PSs) into the dense extracellular polymeric substances (EPS) of biofilms. Herein, we develop a dissolving microneedle (DMN) patch composed of a sulfobutylether-β-cyclodextrin (SCD)/tetra(4-pyridyl)-porphine (TPyP) supramolecular PS for enhanced biofilm penetration and eradication. The inclusion of TPyP into the SCD cavity can drastically inhibit the aggregation of TPyP, thereby allowing for nearly tenfold reactive oxygen species production and high photodynamic antibacterial efficacy. Moreover, the TPyP/SCD-based DMN (TSMN) possesses excellent mechanical performance that can easily pierce the EPS of biofilm with a penetration depth of ∼350 μm, enabling sufficient contact of TPyP with bacteria and optimal photodynamic elimination of bacterial biofilms. Furthermore, TSMN could efficiently eradicate Staphylococcus aureus biofilm infection in vivo with good biosafety. This study offers a promising platform for supramolecular DMN for efficient biofilm elimination and other PDTs.

A Newly Identified Spike Protein Targeted Linear B-Cell Epitope Based Dissolvable Microneedle Array Successfully Eliciting Neutralizing Activities against SARS-CoV-2 Wild-Type Strain in Mice.

Vaccination is a cost-effective medical intervention. Inactivated whole virusor large protein fragments-based severe acute respiratory syndrome coronavirus (SARS-CoV-2) vaccines have high unnecessary antigenic load to induce allergenicity and/orreactogenicity, which can be avoided by peptide vaccines of short peptide fragments that may induce highly targeted immune response. However, epitope identification and peptide delivery remain the major obstacles in developing peptide vaccines. Here, a multi-source data integrated linear B-cell epitope screening strategy is presented and a linear B-cell epitope enriched hotspot region is identified in Spike protein, from which a monomeric peptide vaccine (Epitope25) is developed and applied to subcutaneously immunize wildtype BALB/c mice. Indirect ELISA assay reveals specific and dose-dependent binding between Epitope25 and serum IgG antibodies from immunized mice. The neutralizing activity of sera from vaccinated mice is validated by pseudo and live SARS-CoV-2 wild-type strain neutralization assays. Then a dissolvable microneedle array (DMNA) is developed to pain-freely deliver Epitope25. Compared with intramuscular injection, DMNA and subcutaneous injection elicit neutralizing activities against SARS-CoV-2 wild-type strain as demonstrated by live SARS-CoV-2 virus neutralization assay. No obvious damages are found in major organs of immunized mice. This study may lay the foundation for developing linear B-cell epitope-based vaccines against SARS-CoV-2.

Design, Fabrication and Characterization of Antiemetic Transdermal Patches Loaded Dissolvable Microneedles

Various non-invasive administration has been recently coming as an excellent alternative to conventional administrative mechanism. A transdermal drug delivery system with polymeric microneedles presents the most attractive method among all these because of its low rejection rate, higher bioavailability, super convenience, ease of administration and ease of termination, biodegradable and persistence in the skin care industry. However, the skin physiochemical properties made them to protect the inner environment and this mechanism play as excellent barrier for TDDS, hence polymeric bio dissolvable and biocompatible microneedle can be excellent choice. In this research, we fabricated and characterized the different proportions of polymer blend solution for effective and improved bioavailability and delivery of Ondansetron HCl. We characterized TDDS on progression of mechanically strength determination by folding endurance, flatness study, gelatin sheets beds penetration application, percentage drug content releasement under FT-IR and studied microscopic images the shape and size of microneedle. In addition, desired physical properties and an excellent alternative method had been established with high efficiency inherent to TDDS which expected to find a broad range of application fields.

Buccal mucosal application of dissolvable microneedle patch containing photosensitizer provides effective localized delivery and phototherapy against oral carcinoma

The effectiveness of phototherapy using photosensitizers is limited by the challenges in their delivery at the site of irradiation. Here, we demonstrate the localized application of a photosensitizer-loaded microneedle patch for effective photodynamic and photothermal therapy in oral carcinoma. Indocyanine green (ICG) was studied as a photosensitizer for its effect on oral carcinoma, FaDu cells. Different parameters including concentration, near-infrared (NIR) laser irradiation intensity and irradiation time were optimized while measuring temperature increase and reactive oxygen species (ROS) generation in FaDu cells. A dissolvable microneedle (DMN) patch made of sodium carboxymethyl cellulose and sodium alginate was fabricated by the micromolding technique. DMN showed sufficient mechanical strength for insertion in the excised porcine buccal mucosa. DMN dissolved within 30 s in phosphate buffer and 30 min in the excised buccal mucosa. Confocal microscopy studies revealed DMN penetration up to a depth of 300 µm within the buccal mucosa. ICG-DMN applied on the back of the rat was found to be localized at the application site before and after irradiation using an 808 nm NIR laser. ICG-DMN was applied on the FaDu xenografted tumor model in athymic nude mice. The localized temperature increase and ROS generation significantly (P < 0.05) decreased the tumor volume after ICG-DMN application compared with the control group. In conclusion, DMN can be developed for the localized administration of photosensitizers for phototherapy in oral carcinoma.

Collagen-Based Dissolving Microneedles with Flexible Pedestals: A Transdermal Delivery System for Both Anti-Aging and Skin Diseases.

Biocompatible polymer microneedles (MNs) are emerging as a promising platform for transdermal drug delivery, especially for facial treatments. Therefore, an MN patch in this study uses hydrolyzed collagen (HC) contained in skin cells as the main raw material and adopts a two-step cast method to develop a rapidly dissolving microneedle (DMN) to deliver collagen in a simple and minimally invasive way, allowing the release of the encapsulated drug in the skin. By optimizing the formulation and proportion of HC and auxiliary support materials, the mechanical strength required to pierce the skin is obtained, while the soft pedestal allows for flexibility in application. The DMNs can dissolve completely in the skin within 15min and release within ≈ 8h, and do not cause toxicity or irritation when being applied. In contrast to the ineffectiveness of oral and external application, and the high risk of dermal injection, drug-loaded DMNs overcome the drawbacks of traditional methods with direct penetration and minimally invasive manner, enabling efficient and safe treatment. The successful preparation and research of HC DMNs have innovative and practical significance in this field, and it is expected to become a simple, effective, and popular transdermal drug delivery platform for cosmetics.

Potent immunogenicity and broad-spectrum protection potential of microneedle array patch-based COVID-19 DNA vaccine candidates encoding dimeric RBD chimera of SARS-CoV and SARS-CoV-2 variants

ABSTRACT Breakthrough infections by SARS-CoV-2 variants pose a global challenge to COVID-19 pandemic control, and the development of more effective vaccines of broad-spectrum protection is needed. In this study, we constructed pVAX1-based plasmids encoding receptor-binding domain (RBD) chimera of SARS-CoV-1 and SARS-CoV-2 variants, including pAD1002 (encoding RBDSARS/BA1), pAD1003 (encoding RBDSARS/Beta) and pAD131 (encoding RBDBA1/Beta). Plasmids pAD1002 and pAD131 were far more immunogenic than pAD1003 in terms of eliciting RBD-specific IgG when intramuscularly administered without electroporation. Furthermore, dissolvable microneedle array patches (MAP) greatly enhanced the immunogenicity of these DNA constructs in mice and rabbits. MAP laden with pAD1002 (MAP-1002) significantly outperformed inactivated SARS-CoV-2 virus vaccine in inducing RBD-specific IFN-γ+ effector and memory T cells, and generated T lymphocytes of different homing patterns compared to that induced by electroporated DNA in mice. In consistence with the high titer neutralization results of MAP-1002 antisera against SARS-CoV-2 pseudoviruses, MAP-1002 protected human ACE2-transgenic mice from Omicron BA.1 challenge. Collectively, MAP-based DNA constructs encoding chimeric RBDs of SARS-CoV-1 and SARS-CoV-2 variants, as represented by MAP-1002, are potential COVID-19 vaccine candidates worthy further translational study.

Transdermal drug delivery system of lidocaine hydrochloride based on dissolving gelatin/sodium carboxymethylcellulose microneedles

In this study, it was aimed to introduce a transdermal drug delivery system with dissolving microneedles (DMNs) based on gelatin (GEL) and sodium carboxymethyl cellulose (NaCMC) for lidocaine hydrochloride (LidoHCl) delivery. Different ratios of GEL and NaCMC were mixed, loaded with an active agent of LidoHCl, and treated with glutaraldehyde (GTA) as a crosslinker agent. Prepared hydrogels were cast into a silicon mold. Hereby, microneedles (MNs) with 500 µm height, 35° needle angle, 40-µm tip radius, and 960-µm tip-to-tip distance were fabricated. Samples containing LidoHCl 40%, GEL/NaCMC 5:1 (wt/wt), and polymer/GTA ratio 3.1 (wt/wt) showed the highest drug release ability (t < 10 min) with proper mechanical properties in comparison with other samples. Due to the drug release in a short time (fewer than 10 min), this drug delivery system can be used for rapid local anesthesia for pain relief as well as before minor skin surgeries.Graphical

Micro-pillar tunnel stamp for enhanced transdermal delivery of topical drug formulations.

Dissolving microneedles (DMNs), despite their minimally invasive drug administration, face challenges in skin insertion and drug-loading capacity, which lead to less effective drug delivery. The micro-pillar tunnel stamp (MPTS) was designed to enhance the transdermal delivery efficacy of externally provided topical formulations via the creation of microchannels. The tunnel and canal of the MPTS enable the simultaneous application of DMNs and topical drugs. The application of micro-pillar-polycaprolactone (MP-PCL), which is a DMN made of a slowly dissolving polymer, exhibited a drug permeation rate 1.3-fold and 2.6-fold higher than that of micro-pillar-hyaluronic acid (MP-HA), a DMN made of a rapidly dissolving polymer, and the topical group, respectively. The base diameter of MP-PCL was set to 700 μm for maximized delivery efficacy, achieving 2.8-fold higher L-ascorbic acid accumulation than that of the topical group. In vivo analysis showed that, compared to topical administration, MPTS-delivered lidocaine had 5-fold greater permeation and the MPTS-delivered group showed 1.25-fold higher skin residual amount, confirming enhanced delivery. Thus, the optimized MPTS system can be presented as an attractive alternative to overcome the limitations of the existing MN systems such as incomplete insertion and limited drug-loading capacity, enhancing the delivery of topical formulations in the transdermal market. STATEMENT OF SIGNIFICANCE: We developed a micro-pillar tunnel stamp (MPTS) to enhance the delivery of externally provided topical formulations. The functional tunnel and canal of the MPTS enabled the simultaneous application of a dissolving microneedle (DMN) array insertion and administration of external topical drugs. Upon insertion, the DMNs created skin microchannels that allowed the externally administered drug to diffuse. DMNs were fabricated using polycaprolactone (PCL), a slowly dissolving polymer, to maintain their structure inside the skin and prolong the opening duration of the microchannels. This system achieved significantly improved delivery of topically administered external drugs via integration with slowly dissolving DMNs, while offering the possibility of its development as a universal delivery system for various topical pharmaceuticals.

Design and Evaluation of Dissolvable Microneedles for Treating Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin disease caused predominantly by immune dysregulation. The global impact of AD continues to increase, making it not only a significant public health issue but also a risk factor for progression into other allergic phenotype disorders. Treatment of moderate-to-severe symptomatic AD involves general skin care, restoration of the skin barrier function, and local anti-inflammatory drug combinations, and may also require systemic therapy, which is often associated with severe adverse effects and is occasionally unsuitable for long-term use. The main objective of this study was to develop a new delivery system for AD treatment based on dissolvable microneedles containing dexamethasone incorporated in a dissolvable polyvinyl alcohol/polyvinylpyrrolidone matrix. SEM imaging of the microneedles showed well-structured arrays comprising pyramidal needles, fast drug release in vitro in Franz diffusion cells, an appropriate mechanical strength recorded with a texture analyzer, and low cytotoxicity. Significant clinical improvements, including in the dermatitis score, spleen weights, and clinical scores, were observed in an AD in vivo model using BALB/c nude mice. Taken together, our results support the hypothesis that microneedle devices loaded with dexamethasone have great potential as a treatment for AD and possibly for other skin conditions as well.