Search Results (82)

Background: A transdermal drug delivery system has significant benefits over conventional routes; however, its effectiveness is limited by the barrier properties of the stratum corneum. Dissolving microneedles (DMNs) have emerged as a minimally invasive strategy to enhance drug permeation while improving patient compliance. The integration of advanced fabrication techniques such as 3D printing enables precise control over microneedle geometry and reproducibility. Objective: This study aimed to fabricate and characterize pregabalin-loaded PVA/PVP dissolving microneedle arrays using a 3D-printing-assisted mold fabrication approach for efficient transdermal drug delivery. Methods: Microneedle master molds were fabricated using 3D printing, followed by replication using polydimethylsiloxane (PDMS) to obtain negative molds. Pregabalin-loaded bilayer microneedles were prepared using a micromolding technique with PVA/PVP polymers. The formulation was evaluated through rheological analysis, scanning electron microscopy (SEM), mechanical strength testing, insertion studies, swelling behavior, drug loading efficiency, Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and in vitro drug release studies. Results: The fabricated microneedles exhibited uniform geometry with sharp tips and no structural defects. Rheological analysis confirmed shear-thinning behavior suitable for mold filling. The microneedles demonstrated adequate mechanical strength (~3.3 N/needle) and efficient insertion into the parafilm model. Drug loading efficiency was high (92.4%), indicating effective encapsulation. FTIR analysis confirmed compatibility between drug and polymers, while DSC and XRD results indicated partial amorphization of pregabalin within the polymer matrix. The formulation showed a biphasic drug release profile with an initial burst followed by sustained release, achieving ~96.8% cumulative release over 24 h. Conclusions: The study successfully demonstrates a robust and reproducible 3D-printing-assisted approach for fabricating pregabalin-loaded dissolving microneedles. The developed system exhibited desirable mechanical, physicochemical, and drug release properties, highlighting its potential as an effective transdermal drug delivery platform. Full article

Background: Additive manufacturing provides a rapid and flexible alternative to conventional micromolding for producing microneedle systems. This study evaluates the potential of a cost-effective LCD 3D printer for fabricating microneedle arrays (MNAs) and investigates how the geometry of MNAs and the formulation of hydrogel influence the performance of lidocaine-coated arrays. Methods: Conical and pyramidal MNAs, along with a reservoir plate, were designed and manufactured. Lidocaine-loaded and placebo hydrogels with two different polymer concentrations were prepared for dip-coating using both single and multilayer applications. Mechanical resistance and insertion efficiency were evaluated under controlled compression. The physicochemical behavior of the hydrogels were characterized, including pH, spreadability, adhesiveness, and rheological behavior. The uniformity of the coating was analyzed using 3D confocal microscopy. Drug loading was quantified by HPLC, drug release was studied using Franz diffusion cells, and skin penetration was confirmed by 3D confocal imaging and Raman mapping. Results: Conical microneedles exhibited high mechanical integrity, showing only a 2% reduction in height compared to 4% for pyramidal MNAs. Stronger drug signals were achieved in deeper skin layers with the conical geometry, indicating enhanced penetration, while pyramidal MNAs provided slightly higher lidocaine loading due to their larger lateral surface. Hydrogels with higher polymer content produced more stable, uniform coatings, particularly when applied in three layers. Rapid drug release was observed, with over 70% of the drug delivered within minutes. Conclusions: LCD 3D printing offers a cost-effective approach for fabricating MNAs with suitable structural stability and sharpness. The optimized hydrogel formulation ensured uniform coverage, as well as maximal and consistence penetration, making this platform a promising candidate for the dermal delivery of other potent drugs. Full article

This study aimed to develop dissolving microneedles (MNs) for the buccal delivery of cannabidiol (CBD). CBD is a non-psychotomimetic phytocannabinoid with anti-inflammatory and anxiolytic properties. The MN arrays were produced using micromolding, which has the ability of scalability. However, this approach lacks the ability to customize needle geometry; thus, additive manufacturing was implemented in the study. Digital Light Processing (DLP) printing is a promising way to produce molds with customized MN architecture. In the present study, molds were fabricated from 3D-printed MN arrays to prepare dissolving MNs for buccal administration. Polymeric needles based on Eudragit L100-55 and Eudragit RSPO were produced from reverse molds and they were evaluated regarding their physiochemical and mechanical properties, followed by in vitro and ex vivo studies using porcine buccal mucosa. Visualization studies were conducted using confocal scanning laser microscopy, whereas the membrane integrity of the porcine mucosa upon application of the MNs was assessed by histological evaluation. Our results suggest that the needles can be effectively inserted into the buccal tissue and release the active pharmaceutical ingredient (API) in a controlled manner. This approach offers a patient-friendly alternative to oral CBD delivery, bypassing first-pass metabolism. Full article

Background: Solid microneedles (MNs) are effective transdermal delivery devices but are commonly fabricated from metallic or non-biodegradable materials, raising concerns related to sustainability, waste management, and processing constraints. This study aimed to evaluate the suitability of the biodegradable biopolyester poly(3-hydroxybutyrate-co-3-hydroxyvalerate-co-3-hydroxyhexanoate) (PHBHVHHx) as a structuring material for solvent-free fabrication of solid MN arrays and to assess their mechanical performance, insertion capability, and drug delivery potential. Methods: PHBHVHHx MN arrays were fabricated by solvent-free micromolding at 200 °C. The resulting MNs were morphologically characterized by scanning electron microscopy. Mechanical properties were assessed by axial compression testing, and insertion performance was evaluated using a multilayer Parafilm skin simulant model. Diclofenac sodium was used as a model drug and applied via surface coating using a FucoPol-based formulation. In vitro drug release was assessed in phosphate-buffered saline under sink conditions and quantified by UV–Vis spectroscopy. Results: PHBHVHHx MN arrays consisted of sharp, well-defined conical needles (681 ± 45 µm length; 330 µm base diameter) with micro-textured surfaces. The MNs withstood compressive forces up to 0.25 ± 0.03 N/needle and achieved insertion depths of approximately 396 µm in the Parafilm model. Drug-coated MNs retained adequate mechanical integrity and exhibited a rapid release profile, with approximately 73% of diclofenac sodium released within 10 min. Conclusions: The results demonstrate that PHBHVHHx is a suitable biodegradable thermoplastic for the fabrication of solid MN arrays via a solvent-free process. PHBHVHHx MNs combine adequate mechanical performance, reliable insertion capability, and compatibility with coated drug delivery, supporting their potential as sustainable alternatives to conventional solid MN systems. Full article

Dissolvable microneedles (DMNs) represent an innovative approach to patient-friendly drug delivery, eliminating the need for conventional hypodermic injections. This study reports on the fabrication, Confocal Laser Scanning Microscopy (CLSM)-based optical visualization of drug distribution, and mechanical characterization of maltose-based DMNs impregnated with lignocaine, a local anesthetic. Microneedles were fabricated using a micro-molding technique and dried for nine hours. Structural integrity was evaluated using Field Emission Scanning Electron Microscopy (FESEM); drug distribution was examined via CLSM; and mechanical strength was assessed using nanoindentation. The FESEM results showed uniform microneedle formation with sharp tips and smooth surfaces, averaging 435 µm in height and 116 µm in width, with no significant dimensional variability (p > 0.5). CLSM analysis indicated even distribution of lignocaine throughout the matrix. Mechanical testing showed that each microneedle withstood 0.6 N, surpassing the 0.1 N threshold required for skin insertion. These results support the viability of maltose-based DMNs for local anesthetic delivery, with implications for outpatient, pediatric, and self-administered care settings. Future investigations will include Franz diffusion and in vitro dissolution studies to examine release kinetics. Full article

Background: Conventional insulin injections cannot mimic physiological pancreatic function and often lead to dangerous hypoglycemic events that glucose-responsive systems aim to prevent. Glucose-responsive microneedles (MNs) offer a promising closed-loop alternative. We developed an enzyme-free, glucose-responsive MN patch composed of a PVA/Dextran hydrogel dynamically crosslinked with borax, and evaluated its performance, biosafety, and in vivo efficacy. Methods: MNs were fabricated from PVA/Dextran via micromolding and crosslinked with borax. The formulation was systematically optimized based on mechanical properties and glucose-responsive release kinetics. Physicochemical properties, biosafety (cytotoxicity, skin barrier recovery, boron leaching), and in vivo efficacy in a type 1 diabetic mouse model were evaluated in comparison to a subcutaneous (SC) insulin injection. Results: The optimized MNs showed robust mechanics (per-needle fracture force approximately 1.0 N) for reliable skin penetration. The system demonstrated clear glucose sensitivity, with a release flux ratio ≥1.5 between hyperglycemic (e.g., 400 mg·dL⁻¹) and normoglycemic (100 mg·dL⁻¹) conditions and exhibited excellent reversibility under alternating glucose levels. The patch was highly biocompatible, with >95% cell viability, the only transient skin barrier disruption that fully recovered within 24 h, and had low boron release from patches in vitro. In vivo, the optimized sI-MN patch demonstrated a sustained, glucose-responsive release profile, maintaining blood glucose in diabetic mice near 100 mg·dL⁻¹ for approximately 8 h. This pharmacokinetic profile contrasts markedly with the rapid hypoglycemic nadir and rebound hyperglycemia observed with a standard subcutaneous insulin bolus, highlighting the patch’s potential for mitigating hypoglycemia. Conclusions: The enzyme-free PVA/Dextran/borax MN patch enables autonomous, glucose-responsive insulin delivery. It provides more stable and safer glycemic control than conventional injections by mitigating the risk of hypoglycemia. By mitigating the hypoglycemic risk associated with bolus injections, this systematically optimized platform represents a potential step toward a safer, patient-friendly diabetes therapy, though significant challenges in duration and dose scaling remain. Full article

Background/Objectives: Polymeric microneedles are an innovative drug delivery form combining the benefits of both transdermal and intravenous administration. However, their practical application is limited by fabrication challenges. To address this, the study explores a novel approach for the rapid, precise, and customized production of polymeric microneedles of diverse geometries by utilizing Liquid Crystal Display (LCD) 3D printing technology, marking the first reported use of this technique for microneedle mold fabrication. Methods: LCD 3D printing technology was applied to prepare resin biocompatible microneedle molds. The method developed was optimized by identifying and controlling the critical process parameters (CPPs) through implementing statistical experimental design techniques within the Quality by Design regulatory framework for pharmaceutical development. The optimized molds were subsequently utilized to produce polyvinyl alcohol microneedles with customized shapes and geometries. Representative designs were then loaded with Ropinirole Hydrochloride as a model drug and evaluated in relation to their morphology, drug content, skin insertion depth, and permeability. Results: The application of a Central Composite Design identified layer height and exposure time as the critical process parameters affecting mold fabrication. The optimized design space enabled the selection of printing conditions that maximized dimensional accuracy. Employing these optimum LCD 3D printing parameters, microneedles of various shapes and dimensions were successfully fabricated, exhibiting highly dimensional accuracy. Additionally, tuning skin permeability was proven to be feasible by adjusting microneedle geometry. Conclusions: This work demonstrates the successful use of LCD 3D printing technology in producing biocompatible molds for customized microneedle fabrication, facilitating the development of transdermal delivery systems with personalized drug permeation profiles. Full article

Background/Objectives: Given the overlapping seasonality of influenza (Flu) and respiratory syncytial virus (RSV) infections in human populations, Flu–RSV combination vaccines are urgently needed. However, development of combo-vaccines is often faced with intra-vaccine interference which could compromise vaccination outcomes. Here we present an approach to overcoming this problem using a microneedle array patch (MAP)-based combo-vaccine with minimum intra-vaccine interference. Methods: Vaccine-laden dissolving MAPs were fabricated using a two-step micro-molding process with polyvinyl alcohol as major excipient. A partition-loading strategy was adopted to ensure spatially segregated distribution of a split-virus Flu vaccine and recombinant prefusion protein of RSV in separate MAP sectors. Serum samples from BALB/c mice post-vaccination were assessed for titers of binding and neutralizing antibodies against the viruses. Live virus challenge studies were carried out to assess the protection efficacy of the MAP-based vaccines. Results: Although i.m. administered standalone Flu and RSV vaccines were able to induce strong IgG responses in BALB/c mice, bidirectional intra-vaccine interference was observed when the two vaccines were co-administered in premixed form. However, when the two vaccines were loaded onto nonoverlapping sectors of D-MAPs for intradermal vaccination, the intra-vaccine interference effect was effectively overcome. The partition-loaded MAP-Flu/RSV combo-vaccine elicited antigen-specific IgG with robust virus-neutralizing activity and was strongly efficacious against either virus in challenge studies. Conclusions: Our data provide proof-of-concept evidence for the potential usefulness of partition-loaded MAPs in overcoming a critical barrier in vaccinology and offer a promising platform for future clinical translation. Full article

Strain-promoted azide–alkyne cycloaddition (SPAAC) is widely used in solution-phase bioconjugation. However, its application in surface chemistry remains limited because substrate-independent azide films that remain stable upon reaction with bulky strained alkynes have not yet been developed. In this study, we address this challenge using a melanin-inspired coating based on tyrosine–azide derivatives with different linkers. In particular, we investigated how differences in linker length and hydrophilicity affect the hydrophobic interactions within the film network and, ultimately, determine film stability. Specifically, Tyr-3-N₃, a tyrosine–azide derivative having an azide group tethered to tyrosine through a short three-carbon alkyl linker, was identified as optimal, forming azide-presenting films via tyrosinase-mediated oxidation and retaining integrity during SPAAC with external dibenzocyclooctyne (DBCO) ligands. The optimized poly(Tyr-3-N₃) coatings enabled efficient methoxypolyethylene glycol (mPEG) immobilization, thereby exhibiting excellent antifouling performance against protein adsorption, and further supported spatially controlled protein patterning through soft lithography techniques such as micromolding in capillaries (MIMIC) and microcontact printing (µCP). The approach was broadly applicable with a range of inorganic and polymeric substrates, as well as living cell surfaces; even after encapsulation and SPAAC-based functionalization, the cells remained viable. Collectively, these findings establish a substrate-independent and biocompatible coating platform that preserves film stability through SPAAC functionalization, supporting applications in antifouling coatings, biosensing, and cell surface engineering. Full article

A bioresorbable cannulated bone screw was developed using PLA/PCL-based composites reinforced with hydroxyapatite (HA) and titanium dioxide (TiO₂), two additives previously reported to enhance mechanical compliance, biocompatibility, and molding feasibility in biodegradable polymer systems. The design incorporated a crest-trimmed thread and a strategically positioned gate in the thin-wall zone opposite the hexagonal socket to preserve torque-transmitting geometry during micromolding. To investigate shrinkage behavior, a Taguchi orthogonal array was employed to systematically vary micromolding parameters, generating a structured dataset for training a back-propagation neural network (BPNN). Analysis of variance (ANOVA) identified melt temperature as the most influential factor affecting shrinkage quality, defined by a combination of shrinkage rate and dimensional variation. A hybrid AI framework integrating the BPNN with genetic algorithms and particle swarm optimization (GA–PSO) was applied to predict the optimal shrinkage conditions. This is the first use of BPNN–GA–PSO for cannulated bone screw molding, with the shrinkage rate as a targeted output. The AI-predicted solution, interpolated within the Taguchi design space, achieved improved shrinkage quality over all nine experimental groups. Beyond the specific PLA/PCL-based systems studied, the modeling framework—which combines geometry-specific gate design and normalized shrinkage prediction—offers broader applicability to other bioresorbable polymers and hollow implant geometries requiring high-dimensional fidelity. This study integrates composite formulation, geometric design, and data-driven modeling to advance the precision micromolding of biodegradable orthopedic devices. Full article

Dental caries can cause premature loss of deciduous teeth, affecting children’s growth and development. Endodontic treatment using polymer posts is an effective solution. This study explores biodegradable root canal posts made from Polylactic Acid (PLA), Polycaprolactone (PCL), and amorphous calcium phosphate (ACP), aiming to enhance mechanical properties, minimize polymer degradation acidity, and prevent inflammation. A root canal post with a spherical head and serrated structure was designed and produced via micromolding and optimized using the Taguchi experimental method. The melt temperature, injection speed, and holding speed were analyzed for their influence on shrinkage, revealing an optimal rate of 2.575%, representing the sum of axial and radial shrinkage. The melt temperature had the highest impact (55.932%), followed by holding speed (33.575%), with there being minimal effect from injection speed. The composite exhibited a flexural strength of 21.936 MPa, a modulus of 2.083 GPa, and a hydrophilic contact angle of 73.73 degrees. Cell survival tests confirmed biocompatibility, with a survival rate exceeding 70% and no toxicity. These findings highlight the potential of PLA/PCL/ACP composites, combined with injection molding, for developing biodegradable root canal posts in primary teeth. Full article

Nanoscale amorphous calcium phosphate (ACP) exhibits superior bioactivity, degradability, and osteoblast adhesion compared to hydroxyapatite (HAp), making it a promising bioactive ceramic material for bone regeneration applications. This study explores the integration of ACP as a bioactive additive in polylactic acid/polycaprolactone (PLA/PCL) composites. Nanoscale ACP powder was synthesized through low-temperature wet chemical methods without additional reagents. The composite, consisting of 10 wt.% ACP, 80 wt.% PLA, and 20 wt.% PCL, achieved optimal tensile strength (>12 MPa) and elongation (>0.1%). Utilizing the Taguchi experimental design, the microinjection molding parameters were optimized, and they are a material temperature of 190 °C, an injection speed of 50 mm/s, and a holding pressure speed of 30 mm/s. Variance analysis identified the injection speed to be the most significant factor, contributing 50.73% to the overall effect. Immersing ACP in simulated body fluid (SBF) for six hours reduced its calcium ion concentration by 28%, with this concentration stabilizing thereafter. Biocompatibility was confirmed through an MTT assay with NIH-3T3 cells, demonstrating the PLA/PCL/ACP composite’s compatibility. Bone differentiation and mineralization tests showed the enhanced performance of both ACP and the composite material. Degradation tests indicated an initial 0.29% weight increase in the first week, followed by a 2% reduction by the fifth week. These results underscore the PLA/PCL/ACP composite’s excellent mechanical properties, biocompatibility, and suitability for injection molding, positioning it as a strong candidate for biodegradable bone screw applications. Full article

Effective high-aspect-ratio molds that minimize vacuum processes are becoming increasingly important for producing metalenses and other devices. To fabricate a high-aspect-ratio structure, a metal film must be used as a mask for dry etching, typically achieved via vacuum deposition. To avoid this vacuum process, we devised a method to develop an etching mask in the air using silver ink. The manufacturing method involved filling the mold with silver ink, baking it, removing silver from the convex parts of the mold with a polyethylene terephthalate film, and placing silver from the concave parts of the mold on top of the ultraviolet (UV)-cured resin using ultraviolet-nanoimprint lithography. The transferred pattern had silver on the convex parts, which was used as a mask for the oxygen dry etching of the UV-curable resin. Consequently, high-aspect-ratio resin shapes were obtained from three types of nano- and micromolds. Additionally, a high-aspect-ratio resin with silver was used as a replica mold to form a silver pattern. This process is effective and allows high-aspect-ratio patterns to be obtained from master molds. Full article

Ultrasound micromolding (USM) is an emerging processing technology that offers advantages with regard to spatial resolution, material savings, minimum time residence, minimum exposure to high temperatures, and low cost. Recent advances have been focused on nodal point technology, which improves the homogeneity of the molded samples and the repeatability of the properties of processed specimens. The present work demonstrates the suitability of a modified USM technology to process the biodegradable poly(3-hydroxybutyrate) (P3HB), which is a polymer that has well-reported difficulties when processed by conventional methods. Specifically, conventional injection, microinjection, and USM technologies with and without nodal point configurations have been compared. Degradation studies and the evaluation of thermal and mechanical properties confirmed the successful preparation of P3HB microspecimens, maintaining their functional integrity with minimal molecular weight loss. Exfoliated clay structures were observed for P3HB nanocomposites incorporating the C20 and C166 clays and processed by USM. The results highlight the advantages of the modified USM technology, as conventional microinjection failed to produce nanocomposites of P3HB/C116 due to the enhanced degradation caused by C116. Full article

Background: Skin and soft tissue infections (SSTIs) present significant treatment challenges. These infections often require systemic antibiotics such as vancomycin, which poses a risk for increased bacterial resistance. Topical treatments are hindered by the barrier function of the skin, and microneedles (MNs) offer a promising solution, increasing patient compliance and negating the need for traditional needles. Methods: This study focused on the use of sodium alginate MNs for vancomycin delivery directly to the site of infection via a cost-effective micromolding technique. Dissolving polymeric MNs made of sodium alginate and loaded with vancomycin were fabricated and evaluated in terms of their physical properties, delivery ability, and antimicrobial activity. Results: The MNs achieved a 378 μm depth of insertion into ex vivo skin and a 5.0 ± 0 mm zone of inhibition in agar disc diffusion assays. Furthermore, in ex vivo Franz cell experiments, the MNs delivered 34.46 ± 11.31 μg of vancomycin with around 35% efficiency, with 9.88 ± 0.57 μg deposited in the skin after 24 h. Conclusions: These findings suggest that sodium alginate MNs are a viable platform for antimicrobial agent delivery in SSTIs. Future in vivo studies are essential to confirm the safety and effectiveness of this innovative method for clinical use. Full article