Fabrication of Hybrid Coated Microneedles with Donepezil Utilizing Digital Light Processing and Semisolid Extrusion Printing for the Management of Alzheimer's Disease.

Microneedle (MN) patches are gaining increasing attention as a cost-effective technology for delivering drugs directly into the skin. In the present study, two different 3D printing processes were utilized to produce coated MNs, namely, digital light processing (DLP) and semisolid extrusion (SSE). Donepezil (DN), a cholinesterase inhibitor administered for the treatment of Alzheimer's disease, was incorporated into the coating material. Physiochemical characterization of the coated MNs confirmed the successful incorporation of donepezil as well as the stability and suitability of the materials for transdermal delivery. Optical microscopy and SEM studies validated the uniform weight distribution and precise dimensions of the MN arrays, while mechanical testing ensured the MNs' robustness, ensuring efficient skin penetration. In vitro studies were conducted to evaluate the produced transdermal patches, indicating their potential use in clinical treatment. Permeation studies revealed a significant increase in DN permeation compared to plain coating material, affirming the effectiveness of the MNs in enhancing transdermal drug delivery. Confocal laser scanning microscopy (CLSM) elucidated the distribution of the API, within skin layers, demonstrating sustained drug release and transcellular transport pathways. Finally, cell studies were also conducted on NIH3T3 fibroblasts to evaluate the biocompatibility and safety of the printed objects for transdermal applications.

Tailored Sticky Solutions: 3D-Printed Miconazole Buccal Films for Pediatric Oral Candidiasis.

In this research, 3D-printed antifungal buccal films (BFs) were manufactured as a potential alternative to commercially available antifungal oral gels addressing key considerations such as ease of manufacturing, convenience of administration, enhanced drug efficacy and suitability of paediatric patients. The fabrication process involved the use of a semi-solid extrusion method to create BFs from zein-Poly-Vinyl-Pyrrolidone (zein-PVP) polymer blend, which served as a carrier for drug (miconazole) and taste enhancers. After manufacturing, it was determined that the disintegration time for all films was less than 10 min. However, these films are designed to adhere to buccal tissue, ensuring sustained drug release. Approximately 80% of the miconazole was released gradually over 2 h from the zein/PVP matrix of the 3D printed films. Moreover, a detailed physicochemical characterization including spectroscopic and thermal methods was conducted to assess solid state and thermal stability of film constituents. Mucoadhesive properties and mechanical evaluation were also studied, while permeability studies revealed the extent to which film-loaded miconazole permeates through buccal tissue compared to commercially available oral gel formulation. Histological evaluation of the treated tissues was followed. Furthermore, in vitro antifungal activity was assessed for the developed films and the commercial oral gel. Finally, films underwent a two-month drug stability test to ascertain the suitability of the BFs for clinical application. The results demonstrate that 3D-printed films are a promising alternative for local administration of miconazole in the oral cavity.

In Situ Gelling Electrospun Ocular Films Sustain the Intraocular Pressure-Lowering Effect of Timolol Maleate: In Vitro, Ex Vivo, and Pharmacodynamic Assessment.

Most common intraocular pressure (IOP) reduction regimens for the management of glaucoma include the topical use of eye drops, a dosage form that is associated with short residence time at the site of action, increased dosing frequency, and reduced patient compliance. In situ gelling nanofiber films comprising poly(vinyl alcohol) and Poloxamer 407 were fabricated via electrospinning for the ocular delivery of timolol maleate (TM), aiming to sustain the IOP-lowering effect of the ß-blocker, compared to conventional eye drops. The electrospinning process was optimized, and the physicochemical properties of the developed formulations were thoroughly investigated. The fiber diameters of the drug-loaded films ranged between 123 and 145 nm and the drug content between 5.85 and 7.83% w/w. Total in vitro drug release from the ocular films was attained within 15 min following first-order kinetics, showing higher apparent permeability (Papp) values across porcine corneas compared to the drug's solution. The fabricated films did not induce any ocular irritation as evidenced by both the hen's egg test on chorioallantoic membrane and the in vivo Draize test. In vivo administration of the ocular films in rabbits induced a faster onset of action and a sustained IOP-lowering effect up to 24 h compared to TM solution, suggesting that the proposed ocular films are promising systems for the sustained topical delivery of TM.

Graphene Nanoplatelets' Effect on the Crystallization, Glass Transition, and Nanomechanical Behavior of Poly(ethylene 2,5-furandicarboxylate) Nanocomposites.

Poly(ethylene 2,5-furandicarboxylate) (PEF) nanocomposites reinforced with various content of graphene nanoplatelets (GNPs) were synthesized in situ in this work. PEF is a widely known biobased polyester with promising physical properties and is considered as the sustainable counterpart of PET. Despite its exceptional gas barrier and mechanical properties, PEF presents with a low crystallization rate. In this context, a small number of GNPs were incorporated into the material to facilitate the nucleation and overall crystallization of the matrix. Kinetic analysis of both the cold and melt crystallization processes of the prepared materials was achieved by means of differential scanning calorimetry (DSC). The prepared materials' isothermal crystallization from the glass and melt states was studied using the Avrami and Hoffman-Lauritzen theories. The Dobreva method was applied for the non-isothermal DSC measurements to calculate the nucleation efficiency of the GNPs on the PEF matrix. Furthermore, Vyazovkin's isoconversional method was employed to estimate the effective activation energy values of the amorphous materials' glass transition. Finally, the nanomechanical properties of the amorphous and semicrystalline PEF materials were evaluated via nanoindentation measurements. It is shown that the GNPs facilitate the crystallization process through heterogeneous nucleation and, at the same time, improve the nanomechanical behavior of PEF, with the semicrystalline samples presenting with the larger enhancements.

Development of Water-Soluble Electrospun Fibers for the Oral Delivery of Cannabinoids.

Cannabidiol (CBD) and cannabigerol (CBG) are two active pharmaceutical ingredients, derived from cannabis plant. In the present study, CBD and CBG were formulated with polyvinyl(pyrrolidone) (PVP) and Eudragit L-100, using electrohydrodynamic atomization (electrospinning). The produced fibers were smooth and uniform in shape, with average fiber diameters in the range of 700-900 nm for PVP fibers and 1-5 µm for Eudragit L-100 fibers. The encapsulation efficiency for both CB and CBG was high (over 90%) for all formulations tested. Both in vitro release and disintegration tests of the formulations in simulated gastric fluids (SGF) and simulated intestinal fluids (SIF) indicated the rapid disintegration and dissolution of the fibers and the subsequent rapid release of the drugs. The study concluded that the electrospinning process is a fast and efficient method to produce drug-loaded fibers suitable for the per os administration of cannabinoids.

Inkjet printing of a thermolabile model drug onto FDM-printed substrates: formulation and evaluation.

OBJECTIVE: The inkjet printing (IP) and fused deposition modeling (FDM) technologies have emerged in the pharmaceutical field as novel and personalized formulation approaches. Specific manufacturing factors must be considered in each adopted methodology, i.e. the development of suitable substrates for IP and the incorporation of highly thermostable active pharmaceutical compounds (APIs) for FDM. In this study, IP and FDM printing technologies were investigated for the fabrication of hydroxypropyl methylcellulose-based mucoadhesive films for the buccal delivery of a thermolabile model drug. Significance: This proof-of-concept approach was expected to provide an alternative formulation methodology for personalized mucoadhesive buccal films. METHODS: Mucoadhesive substrates were prepared by FDM and were subjected to sequential IP of an ibuprofen-loaded liquid ink. The interactions between these processes and the performance of the films were evaluated by various analytical and spectroscopic techniques, as well as by in vitro and ex vivo studies. RESULTS: The model drug was efficiently deposited by sequential IP passes onto the FDM-printed substrates. Significant variations were revealed on the morphological, physicochemical and mechanical properties of the prepared films, and linked to the number of IP passes. The mechanism of drug release, the mucoadhesion and the permeation of the drug through the buccal epithelium were evaluated, in view of the extent of ink deposition onto the buccal films, as well as the distribution of the API. CONCLUSIONS: The presented methodology provided a proof-of-concept formulation approach for the development of personalized mucoadhesive films.

Composite Membranes of Poly(ε-caprolactone) with Bisphosphonate-Loaded Bioactive Glasses for Potential Bone Tissue Engineering Applications.

Poly(ε-caprolactone) (PCL) is a bioresorbable synthetic polyester with numerous biomedical applications. PCL membranes show great potential in guided tissue regeneration because they are biocompatible, occlusive and space maintaining, but lack osteoconductivity. Therefore, two different types of mesoporous bioactive glasses (SiO2-CaO-P2O5 and SiO2-SrO-P2O5) were synthesized and incorporated in PCL thin membranes by spin coating. To enhance the osteogenic effect of resulting membranes, the bioglasses were loaded with the bisphosphonate drug ibandronate prior to their incorporation in the polymeric matrix. The effect of the composition of the bioglasses as well as the presence of absorbed ibandronate on the physicochemical, cell attachment and differentiation properties of the PCL membranes was evaluated. Both fillers led to a decrease of the crystallinity of PCL, along with an increase in its hydrophilicity and a noticeable increase in its bioactivity. Bioactivity was further increased in the presence of a Sr substituted bioglass loaded with ibandronate. The membranes exhibited excellent biocompatibility upon estimation of their cytotoxicity on Wharton's Jelly Mesenchymal Stromal Cells (WJ-SCs), while they presented higher osteogenic potential in comparison with neat PCL after WJ-SCs induced differentiation towards bone cells, which was enhanced by a possible synergistic effect of Sr and ibandronate.

Controlled Release of 5-Fluorouracil from Alginate Beads Encapsulated in 3D Printed pH-Responsive Solid Dosage Forms.

Three-dimensional printing is being steadily deployed as manufacturing technology for the development of personalized pharmaceutical dosage forms. In the present study, we developed a hollow pH-responsive 3D printed tablet encapsulating drug loaded non-coated and chitosan-coated alginate beads for the targeted colonic delivery of 5-fluorouracil (5-FU). A mixture of Eudragit® L100-55 and Eudragit® S100 was fabricated by means of hot-melt extrusion (HME) and the produced filaments were printed utilizing a fused deposition modeling (FDM) 3D printer to form the pH-responsive layer of the tablet with the rest comprising of a water-insoluble poly-lactic acid (PLA) layer. The filaments and alginate particles were characterized for their physicochemical properties (thermogravimetric analysis, differential scanning calorimetry, X-ray diffraction), their surface topography was visualized by scanning electron microscopy and the filaments' mechanical properties were assessed by instrumented indentation testing and tensile testing. The optimized filament formulation was 3D printed and the structural integrity of the hollow tablet in increasing pH media (pH 1.2 to pH 7.4) was assessed by means of time-lapsed microfocus computed tomography (µCT). In vitro release studies demonstrated controlled release of 5-FU from the alginate beads encapsulated within the hollow pH-sensitive tablet matrix at pH values corresponding to the colonic environment (pH 7.4). The present study highlights the potential of additive manufacturing in fabricating controlled-release dosage forms rendering them pertinent formulations for further in vivo evaluation.

Innovative Design of a 3D Printed Esophageal Stent Inspired by Nature: Mitigating Migration Challenges in Palliative Esophageal Cancer Therapy.

Esophageal cancer is a complex and challenging tumor to treat, with esophageal stenting being used as a palliative measure to improve the quality of life of patients. Self-expandable metal stents (SEMS), self-expandable plastic stents (SEPS), and biodegradable stents are the most commonly used types of stents. However, complications can arise, such as migration, bleeding, and perforation. To address issues of migration, this study developed a novel 3D printed bioinspired esophageal stent utilizing a highly flexible and ductile TPU material. The stent was designed to be self-expanding and tubular with flared ends to provide secure anchorage at both the proximal and distal ends of the structure. Suction cups were strategically placed around the shaft of the stent to prevent migration. The stent was evaluated through compression-recovery, self-expansion, and anti-migration tests to evaluate its recovery properties, self-expansion ability, and anchoring ability, respectively. The results indicated that the novel stent was able to recover its shape, expand, keep the esophagus open, and resist migration, demonstrating its potential for further research and clinical applications. Finite element analysis (FEA) was leveraged to analyze the stent's mechanical behavior, providing insights into its structural integrity, self-expansion capability, and resistance against migration. These results, supported by FEA, highlight the potential of this innovative stent for further research and its eventual application in preclinical settings.

Nanoindentation Creep Behavior of Additively Manufactured H13 Steel by Utilizing Selective Laser Melting Technology.

Nowadays, H13 hot work steel is a commonly used hot work die material in the industry; however, its creep behavior for additively manufactured H13 steel parts has not been widely investigated. This research paper examines the impact of volumetric energy density (VED), a critical parameter in additive manufacturing (AM), and the effect of post heat-treatment nitrification on the creep behavior of H13 hot work tool steel, which is constructed through selective laser melting (SLM), which is a powder bed fusion process according to ISO/ASTM 52900:2021. The study utilizes nanoindentation tests to investigate the creep response and the associated parameters such as the steady-state creep strain rate. Measurements and observations taken during the holding phase offer a valuable understanding of the behavior of the studied material. The findings of this study highlight a substantial influence of both VED and nitrification on several factors including hardness, modulus of elasticity, indentation depth, and creep displacement. Interestingly, the creep strain rate appears to be largely unaltered by these parameters. The study concludes with the observation that the creep stress exponent (n) shows a decreasing trend with an increase in VED and the application of nitrification treatment.

Development of mucoadhesive 3D-printed Carbopol/Eudragit/SNAC tablets for the oral delivery of enoxaparin: In vitro and ex vivo evaluation.

3D-printed dosage forms comprised of Carbopol and Eudragit were fabricated through semi-solid extrusion, combining Enoxaparin (Enox) and the permeation enhancer SNAC in a single-step process without subsequent post-processing. Inks were characterized using rheology and Fourier-transform infrared (FTIR) spectroscopy. The stability of Enox in the fabricated dosage forms was assessed by means of Nuclear Magnetic Resonance (NMR) and Circular Dichroism (CD) analysis. In vitro release studies revealed the release of Enox in a sustained manner, whereas ex vivo experiments demonstrated the mucoadhesive properties of the 3D-printed dosage forms and their ability to enhance Enox permeability across intestinal mucosa. Cellular assays (CCK-8 assay) revealed a dose- and time-dependent response following incubation with the 3D-printed dosage forms. The encapsulation of SNAC in the 3D-printed dosage forms demonstrated their capacity to increase the transcellularly transport of macromolecule across Caco-2 monolayer in a reversible manner, as confirmed by Transepithelial Resistance (TEER) measurements.

Evaluation of 3D-Printed Solid Microneedles Coated with Electrosprayed Polymeric Nanoparticles for Simultaneous Delivery of Rivastigmine and N-Acetyl Cysteine.

In the current study, coated microneedle arrays were fabricated by means of digital light processing (DLP) printing. Three different shapes were designed, printed, and coated with PLGA particles containing two different actives. Rivastigmine (RIV) and N-acetyl-cysteine (NAC) were coformulated via electrohydrodynamic atomization (EHDA), and they were incorporated into the PLGA particles. The two actives are administered as a combined therapy for Alzheimer's disease. The printed arrays were evaluated regarding their ability to penetrate skin and their mechanical properties. Optical microscopy and scanning electron microscopy (SEM) were employed to further characterize the microneedle structure. Confocal laser microscopy studies were conducted to construct 3D imaging of the coating and to simulate the diffusion of the particles through artificial skin samples. Permeation studies were performed to investigate the transport of the drugs across human skin ex vivo. Subsequently, a series of tape strippings were performed in an attempt to examine the deposition of the APIs on and within the skin. Light microscopy and histological studies revealed no drastic effects on the membrane integrity of the stratum corneum. Finally, the cytocompatibility of the microneedles and their precursors was evaluated by measuring cell viability (MTT assay and live/dead staining) and membrane damages followed by LDH release.

Effect of Nanoceria Suspension Addition on the Physicochemical and Mechanical Properties of Hybrid Organic-Inorganic Hydroxyapatite Composite Scaffolds.

In the current study, the synthesis of hydroxyapatite-ceria (HAP-CeO2) scaffolds is attempted through a bioinspired chemical approach. The utilized colloidal CeO2 suspension presents antifungal activity against the Aspergillus flavus and Aspergillus fumigatus species at concentrations higher than 86.1 ppm. Three different series of the composite HAP-CeO2 suspensions are produced, which are differentiated based on the precursor suspension to which the CeO2 suspension is added and by whether this addition takes place before or after the formation of the hydroxyapatite phase. Each of the series consists of three suspensions, in which the pure ceria weight reaches 4, 5, and 10% (by mass) of the produced hydroxyapatite, respectively. The characterization showed that the 2S series's specimens present the greater alteration towards their viscoelastic properties. Furthermore, the 2S series's sample with 4% CeO2 presents the best mechanical response. This is due to the growth of needle-like HAP crystals during lyophilization, which-when oriented perpendicular to the direction of stress application-enhance the resistance of the sample to deformation. The 2S series's scaffolds had an average pore size equal to 100 µm and minimum open porosity 89.5% while simultaneously presented the lowest dissolution rate in phosphate buffered saline.

Fabrication of 3D-printed octreotide acetate-loaded oral solid dosage forms by means of semi-solid extrusion printing.

Semi-solid extrusion (SSE) 3D printing technology was utilized for the encapsulation of octreotide acetate (OCT) into 3D-printed oral dosage forms in ambient conditions. The inks and the OCT-loaded 3D-printed oral dosage forms were characterized by means of rheology, Fourier-transform infrared (FTIR) spectroscopy and Nuclear Magnetic Resonance (NMR). In vitro studies demonstrated that the formulations released OCT in a controlled manner. The application of these formulations to Caco-2 cell monolayers revealed their capability to induce the transient opening of tight junctions in a reversible manner as evidenced by Transepithelial Resistance (TEER) measurements. Cellular assays (CCK-8 assay) demonstrated the viability of intestinal cells in the presence of these formulations. The in vitro transport studies across Caco-2 monolayers demonstrated the ability of these formulations to enhance the OCT uptake across the cell monolayer over time due to opening of the tight junctions.

Development of biodegradable customized tibial scaffold with advanced architected materials utilizing additive manufacturing.

In the last decade, the development of customized biodegradable scaffolds and implants has attracted increased scientific interest due to the fact that additive manufacturing technologies allow for the rapid production of implants with high geometric complexity constructed via commercial biodegradable polymers. In this study, innovative designs of tibial scaffold in form of bone-brick configuration were developed to fill the bone gap utilizing advanced architected materials and bio-inspired diffusion canals. The architected materials and canals provide high porosity, as well as a high surface area to volume ratio in the scaffold facilitating that way in the tissue regeneration process and in withstanding the applied external loads. The cellular structures applied in this work were the Schwarz Diamond (SD) and a hybrid SD&FCC hybrid cellular material, which is a completely new architected material that derived from the combination of SD and Face Centered Cubic (FCC) structures. These designs were additively manufactured utilizing two biodegradable materials namely Polylactic acid (PLA) and Polycaprolactone (PCL), using the Fused Filament Fabrication (FFF) technique, in order to avoid the surgery, for the scaffold's removal after the bone regeneration. Furthermore, the additively manufactured scaffolds were examined in terms of compatibility and assembly with the bone's physical model, as well as, in terms of mechanical behavior under realistic static loads. In addition, non-linear finite element models (FEMs) were developed based on the experimental data to accurately simulate the mechanical response of the examined scaffolds. The Finite Element Analysis (FEA) results were compared with the experimental response and afterwards the stress concentration regions were observed and identified. Τhe proposed design of scaffold with SD&FCC lattice structure made of PLA material with a relative density of 20% revealed the best overall performance, showing that it is the most suitable candidate for further investigation (in-vivo test, clinical trials, etc.) and commercialization.

Novel 3D-Printed Biocarriers from Aluminosilicate Materials.

The addition of biocarriers can improve biological processes in bioreactors, since their surface allows for the immobilization, attachment, protection, and growth of microorganisms. In addition, the development of a biofilm layer allows for the colonization of microorganisms in the biocarriers. The structure, composition, and roughness of the biocarriers' surface are crucial factors that affect the development of the biofilm. In the current work, the aluminosilicate zeolites 13X and ZSM-5 were examined as the main building components of the biocarrier scaffolds, using bentonite, montmorillonite, and halloysite nanotubes as inorganic binders in various combinations. We utilized 3D printing to form pastes into monoliths that underwent heat treatment. The 3D-printed biocarriers were subjected to a mechanical analysis, including density, compression, and nanoindentation tests. Furthermore, the 3D-printed biocarriers were morphologically and structurally characterized using nitrogen adsorption at 77 K (LN2), scanning electron microscopy (SEM), and X-ray diffraction (XRD). The stress-strain response of the materials was obtained through nanoindentation tests combined with the finite element analysis (FEA). These tests were also utilized to simulate the lattice geometries under compression loading conditions to investigate their deformation and stress distribution in relation to experimental compression testing. The results indicated that the 3D-printed biocarrier of 13X/halloysite nanotubes was endowed with a high specific surface area of 711 m2/g and extended mesoporous structure. Due to these assets, its bulk density of 1.67 g/cm3 was one of the lowest observed amongst the biocarriers derived from the various combinations of materials. The biocarriers based on the 13X zeolite exhibited the highest mechanical stability and appropriate morphological features. The 13X/halloysite nanotubes scaffold exhibited a hardness value of 45.64 MPa, which is moderate compared to the rest, while it presented the highest value of modulus of elasticity. In conclusion, aluminosilicate zeolites and their combinations with clays and inorganic nanotubes provide 3D-printed biocarriers with various textural and structural properties, which can be utilized to improve biological processes, while the most favorable characteristics are observed when utilizing the combination of 13X/halloysite nanotubes.

Effect of Monomer Type on the Synthesis and Properties of Poly(Ethylene Furanoate).

This work aimed to produce bio-based poly(ethylene furanoate) (PEF) with a high molecular weight using 2,5-furan dicarboxylic acid (FDCA) or its derivative dimethyl 2,5-furan dicarboxylate (DMFD), targeting food packaging applications. The effect of monomer type, molar ratios, catalyst, polycondensation time, and temperature on synthesized samples' intrinsic viscosities and color intensity was evaluated. It was found that FDCA is more effective than DMFD in producing PEF with higher molecular weight. A sum of complementary techniques was employed to study the structure-properties relationships of the prepared PEF samples, both in amorphous and semicrystalline states. The amorphous samples exhibited an increase in glass transition temperature of 82-87 °C, and annealed samples displayed a decrease in crystallinity with increasing intrinsic viscosity, as analyzed by differential scanning calorimetry and X-ray diffraction. Dielectric spectroscopy showed moderate local and segmental dynamics and high ionic conductivity for the 2,5-FDCA-based samples. The spherulite size and nuclei density of samples improved with increased melt crystallization and viscosity, respectively. The hydrophilicity and oxygen permeability of the samples were reduced with increased rigidity and molecular weight. The nanoindentation test showed that the hardness and elastic modulus of amorphous and annealed samples is higher at low viscosities due to high intermolecular interactions and degree of crystallinity.

Poly(Lactic Acid) Composites with Lignin and Nanolignin Synthesized by In Situ Reactive Processing.

Poly(lactic acid) (PLA) composites with 0.5 wt% lignin or nanolignin were prepared with two different techniques: (a) conventional melt-mixing and (b) in situ Ring Opening Polymerization (ROP) by reactive processing. The ROP process was monitored by measuring the torque. The composites were synthesized rapidly using reactive processing that took under 20 min. When the catalyst amount was doubled, the reaction time was reduced to under 15 min. The dispersion, thermal transitions, mechanical properties, antioxidant activity, and optical properties of the resulting PLA-based composites were evaluated with SEM, DSC, nanoindentation, DPPH assay, and DRS spectroscopy. All reactive processing-prepared composites were characterized by means of SEM, GPC, and NMR to assess their morphology, molecular weight, and free lactide content. The benefits of the size reduction of lignin and the use of in situ ROP by reactive processing were demonstrated, as the reactive processing-produced nanolignin-containing composites had superior crystallization, mechanical, and antioxidant properties. These improvements were attributed to the participation of nanolignin in the ROP of lactide as a macroinitiator, resulting in PLA-grafted nanolignin particles that improved its dispersion.

Fabrication of 3D Printed Hollow Microneedles by Digital Light Processing for the Buccal Delivery of Actives.

In the present study, two different microneedle devices were produced using digital light processing (DLP). These devices hold promise as drug delivery systems to the buccal tissue as they increase the permeability of actives with molecular weights between 600 and 4000 Da. The attached reservoirs were designed and printed along with the arrays as a whole device. Light microscopy was used to quality control the printability of the designs, confirming that the actual dimensions are in agreement with the digital design. Non-destructive volume imaging by means of microfocus computed tomography was employed for dimensional and defect characterization of the DLP-printed devices, demonstrating the actual volumes of the reservoirs and the malformations that occurred during printing. The penetration test and finite element analysis showed that the maximum stress experienced by the needles during the insertion process (10 N) was below their ultimate compressive strength (240-310 N). Permeation studies showed the increased permeability of three model drugs when delivered with the MN devices. Size-exclusion chromatography validated the stability of all the actives throughout the permeability tests. The safety of these printed devices for buccal administration was confirmed by histological evaluation and cell viability studies using the TR146 cell line, which indicated no toxic effects.

Synthesis of Poly(ethylene furanoate) Based Nanocomposites by In Situ Polymerization with Enhanced Antibacterial Properties for Food Packaging Applications.

Poly(ethylene 2,5-furandicarboxylate) (PEF)-based nanocomposites containing Ce-bioglass, ZnO, and ZrO2 nanoparticles were synthesized via in situ polymerization, targeting food packaging applications. The nanocomposites were thoroughly characterized, combining a range of techniques. The successful polymerization was confirmed using attenuated total reflectance Fourier-transform infrared (ATR-FTIR) spectroscopy, and the molecular weight values were determined indirectly by applying intrinsic viscosity measurements. The nanocomposites' structure was investigated by depth profiling using time-of-flight secondary ion mass spectrometry (ToF-SIMS), while color measurements showed a low-to-moderate increase in the color concentration of all the nanocomposites compared to neat PEF. The thermal properties and crystallinity behavior of the synthesized materials were also examined. The neat PEF and PEF-based nanocomposites show a crystalline fraction of 0-5%, and annealed samples of both PEF and PEF-based nanocomposites exhibit a crystallinity above 20%. Furthermore, scanning electron microscopy (SEM) micrographs revealed that active agent nanoparticles are well dispersed in the PEF matrix. Contact angle measurements showed that incorporating nanoparticles into the PEF matrix significantly reduces the wetting angle due to increased roughness and introduction of the polar -OH groups. Antimicrobial studies indicated a significant increase in inhibition of bacterial strains of about 9-22% for Gram-positive bacterial strains and 5-16% for Gram-negative bacterial strains in PEF nanocomposite films, respectively. Finally, nanoindentation tests showed that the ZnO-based nanocomposite exhibits improved hardness and elastic modulus values compared to neat PEF.