Dental biomaterials redefined: molecular docking and dynamics-driven dental resin composite optimization.

BACKGROUND: Dental resin-based composites are widely recognized for their aesthetic appeal and adhesive properties, which make them integral to modern restorative dentistry. Despite their advantages, adhesion and biomechanical performance challenges persist, necessitating innovative strategies for improvement. This study addressed the challenges associated with adhesion and biomechanical properties in dental resin-based composites by employing molecular docking and dynamics simulation. METHODS: Molecular docking assesses the binding energies and provides valuable insights into the interactions between monomers, fillers, and coupling agents. This investigation prioritizes SiO2 and TRIS, considering their consistent influence. Molecular dynamics simulations, executed with the Forcite module and COMPASS II force field, extend the analysis to the mechanical properties of dental composite complexes. The simulations encompassed energy minimization, controlled NVT and NPT ensemble simulations, and equilibration stages. Notably, the molecular dynamics simulations spanned a duration of 50 ns. RESULTS: SiO2 and TRIS consistently emerged as influential components, showcasing their versatility in promoting solid interactions. A correlation matrix underscores the significant roles of van der Waals and desolvation energies in determining the overall binding energy. Molecular dynamics simulations provide in-depth insights into the mechanical properties of dental composite complexes. HEMA-SiO2-TRIS excelled in stiffness, BisGMA-SiO2-TRIS prevailed in terms of flexural strength, and EBPADMA-SiO2-TRIS offered a balanced combination of mechanical properties. CONCLUSION: These findings provide valuable insights into optimizing dental composites tailored to diverse clinical requirements. While EBPADMA-SiO2-TRIS demonstrates distinct strengths, this study emphasizes the need for further research. Future investigations should validate the computational findings experimentally and assess the material's response to dynamic environmental factors.

[Preparation technology comparison and performance evaluation of different protein A affinity chromatographic materials].

Protein A affinity chromatographic materials are widely used in clinical medicine and biomedicine because of their specific interactions with immunoglobulin G (IgG). Both the characteristics of the matrix, such as its structure and morphology, and the surface modification method contribute to the affinity properties of the packing materials. The specific, orderly, and oriented immobilization of protein A can reduce its steric hindrance with the matrix and preserve its bioactive sites. In this study, four types of affinity chromatographic materials were obtained using agarose and polyglycidyl methacrylate (PGMA) spheres as substrates, and multifunctional epoxy and maleimide groups were used to fix protein A. The effects of the ethylenediamine concentration, reaction pH, buffer concentration, and other conditions on the coupling efficiency of protein A and adsorption performance of IgG were evaluated. Multifunctional epoxy materials were prepared by converting part of the epoxy groups of the agarose and PGMA matrices into amino groups using 0.2 and 1.6 mol/L ethylenediamine, respectively. Protein A was coupled to the multifunctional epoxy materials using 5 mmol/L borate buffer (pH 8) as the reaction solution. When protein A was immobilized on the substrates by maleimide groups, the agarose and PGMA substrates were activated with 25% (v/v) ethylenediamine for 16 h to convert all epoxy groups into amino groups. The maleimide materials were then converted into amino-modified materials by adding 3 mg/mL 3-maleimidobenzoyl-N-hydroxysuccinimide ester (MBS) dissolved in dimethyl sulfoxide (DMSO) and then suspended in 5 mmol/L borate buffer (pH 8). The maleimide groups reacted specifically with the C-terminal of the sulfhydryl group of recombinant protein A to achieve highly selective fixation on both the agarose and PGMA substrates. The adsorption performance of the affinity materials for IgG was improved by optimizing the bonding conditions of protein A, such as the matrix type, matrix particle size, and protein A content, and the adsorption properties of each affinity material for IgG were determined. The column pressure of the protein A affinity materials prepared using agarose or PGMA as the matrix via the maleimide method was subsequently evaluated at different flow rates. The affinity materials prepared with PGMA as the matrix exhibited superior mechanical strength compared with the materials prepared with agarose. Moreover, an excellent linear relationship between the flow rate and column pressure of 80 mL/min was observed for this affinity material. Subsequently, the effect of the particle size of the PGMA matrix on the binding capacity of IgG was investigated. Under the same protein A content, the dynamic binding capacity of the affinity materials on the PGMA matrix was higher when the particle size was 44-88 µm than when other particle sizes were used. The properties of the affinity materials prepared using the multifunctional epoxy and maleimide-modified materials were compared by synthesizing affinity materials with different protein A coupling amounts of 1, 2, 4, 6, 8, and 10 mg/mL. The dynamic and static binding capacities of each material for bovine IgG were then determined. The prepared affinity material was packed into a chromatographic column to purify IgG from bovine colostrum. Although all materials showed specific adsorption selectivity for IgG, the affinity material prepared by immobilizing protein A on the PGMA matrix with maleimide showed significantly better performance and achieved a higher dynamic binding capacity at a lower protein grafting amount. When the protein grafting amount was 15.71 mg/mL, the dynamic binding capacity of bovine IgG was 32.23 mg/mL, and the dynamic binding capacity of human IgG reached 54.41 mg/mL. After 160 cycles of alkali treatment, the dynamic binding capacity of the material reached 94.6% of the initial value, indicating its good stability. The developed method is appropriate for the production of protein A affinity chromatographic materials and shows great potential in the fields of protein immobilization and immunoadsorption material synthesis.

Evaluating flexure properties, hardness, roughness and microleakage of high-strength injectable dental composite: an in vitro study.

BACKGROUND: Recently, a new generation of high-strength flowable dental composites has been introduced by manufacturers. The manufacturers claim that these materials have enhanced mechanical and physical properties and are suitable for use in a wide range of direct anterior and posterior restorations, even in high-stress bearing areas. AIM: The objective of this study was to assess certain physical and mechanical properties of these recently introduced high-strength flowable composites in comparison to conventional multipurpose dental composites. METHODS: Four types of high-strength flowable composites (Genial Universal FLO, Gaenial Universal Injectable, Beautifil Injectable, and Beautifil Flow Plus) were tested in experimental groups, while a nanohybrid conventional composite (Filtek Z350 XT) was used as the control. For flexure properties, ten rectangular samples (2 × 2 × 25 mm) were prepared from each composite material and subjected to 5000 cycles of thermocycling. Samples were then subjected to flexural strength testing using the universal testing machine. Another twenty disc-shaped specimens of dimensions (5 mm diameter × 2 mm thickness) were fabricated from each composite material for surface roughness (Ra) (n = 10) and hardness (VHN) test (n = 10). All samples underwent 5000 cycles of thermocycling before testing. Additionally, microleakage testing was conducted on 60 standardized class V cavities prepared on molar teeth and divided randomly into five groups (n = 12). Cavities were then filled with composite according to the manufacturer's instructions and subjected to thermocycling for 1000 cycles before testing using methylene blue solution and a stereomicroscope. RESULTS: All tested materials were comparable to the control group in terms of flexural strength and surface roughness (p > 0.05), with Gaenial Universal FLO exhibiting significantly higher flexural strength compared to the other flowable composite materials tested. However, all tested materials demonstrated significantly lower elastic modulus and surface hardness than the control group (p < 0.05). The control group exhibited higher microleakage scores, while the lowest scores were observed in the Gaenial Universal FLO material (p < 0.05) CONCLUSION: The physical and mechanical behaviors of the different high-strength flowable composites investigated in this study varied. Some of these materials may serve as suitable alternatives to conventional composites in specific applications, emphasizing the importance of dentists being familiar with material properties before making material selections.

Eudragit L100-coated nintedanib nanocrystals improve oral bioavailability by reducing drug particle size and maintaining drug supersaturation.

The aim of this study was to prepare nintedanib nanocrystals (BIBF-NCs) to lower the solubility of the drug in the stomach, maintain the supersaturation of the drug in the intestine, and improve the oral absorption of nintedanib (BIBF). In this study, BIBF-NCs were prepared by acid solubilization and alkaline precipitation following nano granding method, with a particle size of 290.80 nm and a zeta potential of -49.13 mV. Subsequently, Nintedanib enteric-coated nanocrystals (BIBF-NCs@L100) were obtained by coating with Eudragit L100. The microscopic morphology, crystalline characteristics, stability, and in vitro dissolution of BIBF-NCs and BIBF-NCs@L100 were also studied. In addition, the in vivo pharmacokinetic behaviors of Samples prepared according to the prescription process of commercially available soft capsules (soft capsules), BIBF-NCs, and BIBF-NCs@L100 were further investigated. The results showed that the oral bioavailability of BIBF-NCs and BIBF-NCs@L100 were increased by 1.43 and 2.58 times, compared with that of the soft capsules. BIBF-NCs@L100 effectively reduced the release of BIBF in the formulation in the stomach, allowing more drug to reach the intestine in the form of nanocrystals, maintaining the supersaturation in the intestine, thereby improving the oral bioavailability of the drug.

Arginine-Functional Methacrylic Block Copolymer Nanoparticles: Synthesis, Characterization, and Adsorption onto a Model Planar Substrate.

Recently, we reported the synthesis of a hydrophilic aldehyde-functional methacrylic polymer (Angew. Chem., 2021, 60, 12032-12037). Herein we demonstrate that such polymers can be reacted with arginine in aqueous solution to produce arginine-functional methacrylic polymers without recourse to protecting group chemistry. Careful control of the solution pH is essential to ensure regioselective imine bond formation; subsequent reductive amination leads to a hydrolytically stable amide linkage. This new protocol was used to prepare a series of arginine-functionalized diblock copolymer nanoparticles of varying size via polymerization-induced self-assembly in aqueous media. Adsorption of these cationic nanoparticles onto silica was monitored using a quartz crystal microbalance. Strong electrostatic adsorption occurred at pH 7 (Γ = 14.7 mg m-2), whereas much weaker adsorption occurred at pH 3 (Γ = 1.9 mg m-2). These findings were corroborated by electron microscopy, which indicated a surface coverage of 42% at pH 7 but only 5% at pH 3.

Spray drying Eudragit® E-PO with acetaminophen using 2- and 3-fluid nozzles for taste masking.

Conventional spray drying using a 2-fluid nozzle forms matrix microparticles, where drug is distributed throughout the particle and may not effectively mask taste. In contrast, spray drying using a 3-fluid nozzle has been reported to encapsulate material. The objective of this study was to spray dry Eudragit® E-PO (EE) with acetaminophen (APAP), a water-soluble model drug with a bitter taste, using 2- and 3-fluid nozzles for taste masking. Spray drying EE with APAP, however, resulted in yields of ≤ 13 %, irrespective of nozzle configuration. Yields improved when Eudragit® L 100-55 (EL) or Methocel® E6 (HPMC) was used in the inner fluid stream of the 3-fluid nozzle or in place of EE for the 2-fluid nozzle. Drug release from microparticles prepared with the 2-fluid nozzle was relatively rapid. Using EE in the outer fluid stream of the 3-fluid nozzle resulted in comparatively slower drug release, although drug release was observed, indicating that encapsulation was incomplete. Results from these studies also show that miscible polymers used in the two fluid streams mix during the spray drying process. In addition, findings from this study indicate that the polymer used in the inner fluid stream can impact drug release.

Development of pH-responsive Eudragit S100-functionalized silk fibroin nanoparticles as a prospective drug delivery system.

Silk fibroin nanoparticles (FNP) have been increasingly investigated in biomedical fields due to their biocompatibility and biodegradability properties. To widen the FNP versatility and applications, and to control the drug release from the FNP, this study developed the Eudragit S100-functionalized FNP (ES100-FNP) as a pH-responsive drug delivery system, by two distinct methods of co-condensation and adsorption, employing the zwitterionic furosemide as a model drug. The particles were characterized by sizes and zeta potentials (DLS method), morphology (electron microscopy), drug entrapment efficiency and release profiles (UV-Vis spectroscopy), and chemical structures (FT-IR, XRD, and DSC). The ES100-FNP possessed nano-sizes of ∼200-350 nm, zeta potentials of ∼ -20 mV, silk-II structures, enhanced thermo-stability, non-cytotoxic to the erythrocytes, and drug entrapment efficiencies of 30%-60%, dependent on the formulation processes. Interestingly, the co-condensation method yielded the smooth spherical particles, whereas the adsorption method resulted in durian-shaped ones due to furosemide re-crystallization. The ES100-FNP adsorbed furosemide via physical adsorption, followed Langmuir model and pseudo-second-order kinetics. In the simulated oral condition, the particles could protect the drug in the stomach (pH 1.2), and gradually released the drug in the intestine (pH 6.8). Remarkably, in different pH conditions of 6.8, 9.5, and 12, the ES100-FNP could control the furosemide release rates depending on the formulation methods. The ES100-FNP made by the co-condensation method was mainly controlled by the swelling and corrosion process of ES100, and followed the Korsmeyer-Peppas non-Fickian transport mechanism. Whereas, the ES100-FNP made by the adsorption method showed constant release rates, followed the zero-order kinetics, due to the gradual furosemide dissolution in the media. Conclusively, the ES100-FNP demonstrated high versatility as a pH-responsive drug delivery system for biomedical applications.

A new method of adhesive system application improves the bond strength between fiber post and root dentin.

This study evaluated a new method of adhesive system application on the bond strength between fiber post and root dentin using two adhesive systems. The canals of sixty bovine incisors were prepared and obturated. The roots were divided into six groups (n=10) according to the adhesive system (Clearfil SE - CSE and Single Bond Universal - SBU) and the application strategy (microbrush - MB; rotary brush - RB; and ultrasonic tip - US). The glass fiber posts were cemented with resin cement (RelyX ARC). The roots were sectioned perpendicularly to their long axis, and three slices per root were obtained. Previously to the push-out test, confocal laser scanning microscopy (CLSM) was performed to illustrate the interfacial adaptation of the cement to the root canal walls. Failure patterns were analyzed with 40x magnification. Shapiro-Wilk indicated a normal distribution of the data. The bond strength values were compared using one-way ANOVA and Tukey's tests. Student's T test analyzed the differences between the adhesive systems within each third and protocol. A significance level of 5% was used. CSE with RB showed higher mean bond strength values compared to MB (conventional technique) (P < 0.05). US application resulted in intermediate bond strength values for CSE (P > 0.05). The application of SBU using RB generated higher mean bond strength values compared to MB and US (P < 0.05). Adhesive failures were predominant (65.5%). CSE and SBU application with the new rotary brush improved the bond strength of fiber posts to root dentin compared to the conventional strategy.

Fabrication and evaluation of stable amorphous polymer-drug composite particles via a nozzle-free ultrasonic nebulizer.

We present a promising method for producing amorphous drug particles using a nozzle-free ultrasonic nebulizer with polymers, specifically polyvinylpyrrolidone (PVP), poly(acrylic acid) (PAA), and Eudragit® S 100 (EUD). Model crystalline phase drugs-Empagliflozin, Furosemide, and Ilaprazole-are selected. This technique efficiently produces spherical polymer-drug composite particles and demonstrates enhanced stability against humidity and thermal conditions, compared to the drug-only amorphous particles. The composite particles exhibit improved water dissolution compared to the original crystalline drugs, indicating potential bioavailability enhancements. While there are challenges, including the need for continuous water supply for ultrasonic component cooling, dependency on the solubility of polymers and drugs in volatile organic solvents, and mildly elevated temperatures for solvent evaporation, our method offers significant advantages over traditional approaches. It provides a straightforward, flexible process adaptable to various drug-polymer combinations and consistently yields spherical amorphous solid dispersion (ASD) particles with a narrow size distribution. These attributes make our method a valuable advancement in pharmaceutical drug formulation and delivery.

Preparation of Eudragit S100-pullulan/hydroxypropyl-ß-cyclodextrin complex-Eudragit S100 multilayer nanofiber film for resveratrol colon delivery.

Cyclodextrin-based electrospun nanofibers are promising for encapsulating and preserving unstable compounds, but quick dissolution of certain nanofibers hinders their delivery application. In this study, hydroxypropyl-ß-cyclodextrin (HPßCD) was used as an effective carrier of resveratrol (RSV) to obtain the RSV/HPßCD inclusion complex (HPIC), which was then incorporated into pullulan nanofibers. For enhancement of RSV release toward colon target, multilayer structure with a pullulan/HPIC film sandwiched between two layers of hydrophobic Eudragit S100 (ES100) nanofibers was employed. The relationship between the superiority of the ES100-pullulan/HPIC-ES100 film and its multilayer structure was verified. The intimate interactions of hydrogen bonds between two adjacent layers enhanced thermal stability, and the hydrophobic outer layers improved water contact resistance. According to release results, multilayer films also showed excellent colon-targeted delivery property and approximately 78.58 % of RSV was observed to release in colon stage. In terms of release mechanism, complex mechanism best described RSV colonic release. Additionally, ES100-pullulan/HPIC-ES100 multilayer films performed higher encapsulation efficiency when compared to the structures without HPIC, which further increased the antioxidant activity and total release amount of RSV. These results suggest a promising strategy for designing safe colonic delivery systems based on multilayer and HPIC structures with superior preservation for RSV.

Engineered probiotics with sustained release of interleukin-2 for the treatment of inflammatory bowel disease after oral delivery.

Inflammatory bowel disease (IBD) is a kind of auto-immune disease characterized by disrupted intestinal barrier and mucosal epithelium, imbalanced gut microbiome and deregulated immune responses. Therefore, the restoration of immune equilibrium and gut microbiota could potentially serve as a hopeful approach for treating IBD. Herein, the oral probiotic Escherichia coli Nissle 1917 (ECN) was genetically engineered to express secretable interleukin-2 (IL-2), a kind of immunomodulatory agent, for the treatment of IBD. In our design, probiotic itself has the ability to regulate the gut microenvironment and IL-2 at low dose could selectively promote the generation of regulatory T cells to elicit tolerogenic immune responses. To improve the bioavailability of ECN expressing IL-2 (ECN-IL2) in the gastrointestinal tract, enteric coating Eudragit L100-55 was used to coat ECN-IL2, achieving significantly enhanced accumulation of engineered probiotics in the intestine. More importantly, L100-55 coated ECN-IL2 could effectively activated Treg cells to regulate innate immune responses and gut microbiota, thereby relieve inflammation and repair the colon epithelial barrier in dextran sodium sulfate (DSS) induced IBD. Therefore, genetically and chemically modified probiotics with excellent biocompatibility and efficiency in regulating intestinal microflora and intestinal inflammation show great potential for IBD treatment in the future.

Bioinspired zwitterionic triblock copolymers designed for colloidal drug delivery: 2 - Biological evaluation.

In this work, poly(lactide) nanoparticles were equipped with a bioinspired coating layer based on poly[2-(methacryloyloxy)ethyl phosphorylcholine] and then evaluated when administered to the lungs and after intravenous injection. Compared to the plain counterparts, the chosen zwitterionic polymer shell prevented the coated colloidal formulation from aggregation and conditioned it for lower cytotoxicity, protein adsorption, complement activation and phagocytic cell uptake. Consequently, no interference with the biophysical function of the lung surfactant system could be detected accompanied by negligible protein and cell influx into the bronchoalveolar space after intratracheal administration. When injected into the central compartment, the coated formulation showed a prolonged circulation half-life and a delayed biodistribution to the liver. Taken together, colloidal drug delivery vehicles would clearly benefit from the investigated poly[2-(methacryloyloxy)ethyl phosphorylcholine]-based polymer coatings.

Comparison study of surface-initiated hydrogel coatings with distinct side-chains for improving biocompatibility of polymeric heart valves.

Polymeric heart valves (PHVs) present a promising alternative for treating valvular heart diseases with satisfactory hydrodynamics and durability against structural degeneration. However, the cascaded coagulation, inflammatory responses, and calcification in the dynamic blood environment pose significant challenges to the surface design of current PHVs. In this study, we employed a surface-initiated polymerization method to modify polystyrene-block-isobutylene-block-styrene (SIBS) by creating three hydrogel coatings: poly(2-methacryloyloxy ethyl phosphorylcholine) (pMPC), poly(2-acrylamido-2-methylpropanesulfonic acid) (pAMPS), and poly(2-hydroxyethyl methacrylate) (pHEMA). These hydrogel coatings dramatically promoted SIBS's hydrophilicity and blood compatibility at the initial state. Notably, the pMPC and pAMPS coatings maintained a considerable platelet resistance performance after 12 h of sonication and 10 000 cycles of stretching and bending. However, the sonication process induced visible damage to the pHEMA coating and attenuated the anti-coagulation property. Furthermore, the in vivo subcutaneous implantation studies demonstrated that the amphiphilic pMPC coating showed superior anti-inflammatory and anti-calcification properties. Considering the remarkable stability and optimal biocompatibility, the amphiphilic pMPC coating constructed by surface-initiated polymerization holds promising potential for modifying PHVs.

Long-term effect of exposure to triethylene glycol dimethacrylate (TEGDMA) on male mouse reproduction.

Our study investigated the impact on male mouse fertility and reproduction of long-term (14 weeks) exposure to triethylene glycol dimethacrylate (TEGDMA), a co-monomer of resin-based compounds, at doses of 0.01, 0.1, 1, and 10 ppm. Test and control mice were then paired with sexually mature untreated female mice and their fertility evaluated. Females paired with males exposed to all TEGDMA doses exhibited a significant decline in pregnancy rates, and significant increases in the total embryonic resorption-to-implantation ratio, except for males exposed to 0.01 ppm TEGDMA. Males in the highest dose group (10 ppm) showed significant increases in seminal vesicle and preputial gland weights. They also had significantly higher serum levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH) than the controls, and the 0.01 ppm dosage group for FSH levels. TEGDMA exposure resulted in notable histopathological alterations in the testis, with detachment of germ cells and shedding of germinal epithelium into the tubule lumen. These results strongly indicate that TEGDMA exposure has detrimental consequences on the reproductive abilities and functions in male mice through disruption of the standard hormonal regulation of the reproductive system, leading to changes in spermatogenesis and ultimately leading to decreased fertility.

Engineering pH-sensitive dissolution of lipid-polymer nanoparticles by Eudragit integration impacts plasmid DNA (pDNA) transfection.

Lipid-polymer nanoparticles offer a promising strategy for improving gene nanomedicines by combining the benefits of biocompatibility and stability associated with the individual systems. However, research to date has focused on poly-lactic-co-glycolic acid (PLGA) and resulted in inefficient transfection. In this study, biocompatible Eudragit constructs E100 and RS100 were formulated as lipid-polymer nanoparticles loaded with pDNA expressing red fluorescent protein (RFP) as a model therapeutic. Using a facile nanoprecipitation technique, a core-shell structure stabilised by lipid-polyethylene glycol (PEG) surfactant was produced and displayed resistance to ultracentrifugation. Both cationic polymers E100 (pH-sensitive dissolution at 5) and RS100 (pH-insensitive dissolution) produced 150-200 nm sized particles with a small positive surface charge (+3-5 mV) and high pDNA encapsulation efficiencies (EE) of 75-90%. The dissolution properties of the Eudragit polymers significantly impacted the biological performance in human embryonic kidney cells (HEK293T). Nanoparticles composed of polymer RS100 resulted in consistently high cell viability (80-100%), whereas polymer E100 demonstrated dose-dependent behaviour (20-90% cell viability). The low dissolution of polymer RS100 over the full pH range and the resulting nanoparticles failed to induce RFP expression in HEK293T cells. In contrast, polymer E100-constructed nanoparticles resulted in reproducible and gradually increasing RFP expression of 26-42% at 48-72 h. Intraperitoneal (IP) injection of the polymer E100-based nanoparticles in C57BL/6 mice resulted in targeted RFP expression in mouse testes with favourable biocompatibility one-week post-administration. These findings predicate Eudragit based lipid-polymer nanoparticles as a novel and effective carrier for nucleic acids, which could facilitate pre-clinical evaluation and translation of gene nanomedicines.

Development and evaluation of a pH-responsive Mimosa pudica seed mucilage/ß- cyclodextrin-co-poly(methacrylate) hydrogel for controlled drug delivery: In vitro and in vivo assessment.

In this comprehensive investigation, a novel pH-responsive hydrogel system comprising mimosa seed mucilage (MSM), ß-cyclodextrin (ß-CD), and methacrylic acid (MAA) was developed via free radical polymerization technique to promote controlled drug delivery. The hydrogel synthesis involved strategic variations in polymer, monomer, and crosslinker content in fine-tuning its drug-release properties. The resultant hydrogel exhibited remarkable pH sensitivity, selectively liberating the model drug (Capecitabine = CAP) under basic conditions while significantly reducing release in an acidic environment. Morphological, thermal, and structural analyses proved that CAP has a porous texture, high stability, and an amorphous nature. In vitro drug release experiments showcased a sustained and controlled release profile. Optimum release (85.33 %) results were recorded over 24 h at pH 7.4 in the case of MMB9. Pharmacokinetic evaluation in healthy male rabbits confirmed bioavailability enhancement and sustained release capabilities. Furthermore, rigorous toxicity evaluations and histopathological analyses ensured the safety and biocompatibility of the hydrogel. This pH-triggered drug delivery system can be a promising carrier system for drugs involving frequent administrations.

Preparation and sustained release of diatomite incorporated and Eudragit L100 coated hydroxypropyl cellulose/chitosan aerogel microspheres.

The drug encapsulation efficiency, release rate and time, sustained release, and stimulus-response of carriers are very important for drug delivery. However, these always cannot obtained for the carrier with a single component. To improve the comprehensive performance of chitosan-based carriers for 5-Fu delivery, diatomite-incorporated hydroxypropyl cellulose/chitosan (DE/HPC/CS) composite aerogel microspheres were fabricated for the release of 5-fluorouracil (5-Fu), and the release performance was regulated with the content of diatomite, pH value, and external coating material. Firstly, the 5-Fu loaded DE/HPC/CS composite aerogel microspheres and Eudragit L100 coated microspheres were prepared with cross-linking followed by freeze-drying, and characterized by SEM, EDS, FTIR, XRD, DSC, TG, and swelling. The obtained aerogel microspheres have a diameter of about 0.5 mm, the weight percentage of F and Si elements on the surface are 0.55 % and 0.78 % respectively. The glass transition temperature increased from 179 °C to 181 °C and 185 °C with the incorporation of DE and coating of Eudragit, and the equilibrium swelling percentage of DE/HPC/CS (1.5:3:2) carriers are 101.52 %, 45.27 %, 67.32 % at pH 1.2, 5.0, 7.4, respectively. Then, the effect of DE content on the drug loading efficiency of DE/HPC/CS@5-Fu was investigated, with the increase of DE content, the highest encapsulation efficiency was 82.6 %. Finally, the release behavior of DE incorporated and Eudragit L100 Coated microspheres were investigated under different pH values, and evaluated with four kinetic models. The results revealed that the release rate of 5-Fu decreased with the increase of DE content, sustained release with extending time and pH-responsive were observed for the Eudragit-coated aerogel microspheres.

Mechanochemical Approach to Obtaining a Multicomponent Fisetin Delivery System Improving Its Solubility and Biological Activity.

In this study, binary amorphous solid dispersions (ASDs, fisetin-Eudragit®) and ternary amorphous solid inclusions (ASIs, fisetin-Eudragit®-HP-ß-cyclodextrin) of fisetin (FIS) were prepared by the mechanochemical method without solvent. The amorphous nature of FIS in ASDs and ASIs was confirmed using XRPD (X-ray powder diffraction). DSC (Differential scanning calorimetry) confirmed full miscibility of multicomponent delivery systems. FT-IR (Fourier-transform infrared analysis) confirmed interactions that stabilize FIS's amorphous state and identified the functional groups involved. The study culminated in evaluating the impact of amorphization on water solubility and conducting in vitro antioxidant assays: 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)-ABTS, 2,2-diphenyl-1-picrylhydrazyl-DPPH, Cupric Reducing Antioxidant Capacity-CUPRAC, and Ferric Reducing Antioxidant Power-FRAP and in vitro neuroprotective assays: inhibition of acetylcholinesterase-AChE and butyrylcholinesterase-BChE. In addition, molecular docking allowed for the determination of possible bonds and interactions between FIS and the mentioned above enzymes. The best preparation turned out to be ASI_30_EPO (ASD fisetin-Eudragit® containing 30% FIS in combination with HP-ß-cyclodextrin), which showed an improvement in apparent solubility (126.5 ± 0.1 µg∙mL-1) and antioxidant properties (ABTS: IC50 = 10.25 µg∙mL-1, DPPH: IC50 = 27.69 µg∙mL-1, CUPRAC: IC0.5 = 9.52 µg∙mL-1, FRAP: IC0.5 = 8.56 µg∙mL-1) and neuroprotective properties (inhibition AChE: 39.91%, and BChE: 42.62%).

Carvacrol nanocapsules as a new antifungal strategy: Characterization and evaluation against fungi important for grape quality and to control the synthesis of ochratoxins.

Fungi are a problem for viticulture as they can lead to deterioration of grapes and mycotoxins production. Despite the widespread use of synthetic fungicides to control fungi, their impact on the agricultural ecosystem and human health demand safer and eco-friendly alternatives. This study aimed to produce, characterize and assess the antifungal activity of carvacrol loaded in nanocapsules of Eudragit® and chia mucilage as strategy for controlling Botrytis cinerea, Aspergillus flavus, Aspergillus carbonarius, and Aspergillus niger. Eudragit® and chia mucilage were suitable wall materials, as both favored the encapsulation of carvacrol into nanometric diameter particles. Fourier Transform Infrared Spectroscopy (FTIR) analysis suggested a successful incorporation of carvacrol into both nanocapsules, which was confirmed by presenting a good encapsulation efficiency and loading capacity. Thermogravimetric Analysis (TGA) and Differential Scanning Calorimetry (DSC) analyses revealed adequate thermal resistance. All fungi were sensible to carvacrol treatments and B. cinerea was the most sensitive compared to the Aspergillus species. Lower concentrations of encapsulated carvacrol than the unencapsulated form were required to inhibit fungi in the in vitro and grape assays. Additionally, lower levels of carvacrol (unencapsulated or encapsulated) were used to inhibit fungal growth and ochratoxin synthesis on undamaged grapes in comparison to those superficially damaged, highlighting the importance of management practices designed to preserve berry integrity during cultivation, storage or commercialization. When sublethal doses of carvacrol were used, the growth of A. niger and A. carbonarius was suppressed by at least 45 %, and ochratoxins were not found. The nanoencapsulation of carvacrol using Eudragit® and chia mucilage has proven to be an alternative to mitigate the problems with fungi and mycotoxins faced by the grape and wine sector.

Eudragit S100 coated nanodiamond-based nanoparticles as an oral chemo-photothermal delivery system for local treatment of colon cancer.

Oral colonic nano-drug delivery system has received more and more attention in the treatment of colon cancer due to local precision treatment and reduction of drug system distribution. However, the complex and harsh gastrointestinal environment and the retention of nanoparticles in the colon limit its development. To this end, we designed Eudragit S100 (ES) coated nanoparticles (ES@PND-PEG-TPP/DOX). Polydopamine coated nanodiamond (PND) was modified with amino-functionalized polyethylene glycol (NH2-PEG-NH2) and triphenylphosphine (TPP) successively. Due to the high specific surface area of PND, it can efficiently load the model drug doxorubicin hydrochloride (DOX). In addition, PND also has high photothermal conversion efficiency, generating heat to kill cancer cells under near infrared (NIR) laser, realizing the combination of chemotherapy and photothermal therapy (CT-PTT). TPP modification enhanced nanoparticle uptake by colon cancer cells and prolonged preparations retention time at the colon. ES shell protected the drug from being destroyed and prevented the nanoparticles from sticking to the small intestine. Ex vitro fluorescence imaging showed that TPP modification can enhance the residence time of nanoparticles in the colon. In vivo pharmacodynamics demonstrated that CT-PTT group has the greatest inhibitory effect on tumor growth, which means that the nanocarrier has potential clinical value in the in-situ treatment of colon cancer.