The Impact of the Addition of Vitamins on a Silicone Lining Material to the Oral Mucosa Tissue-Evaluation of the Biocompatibility, Hydrolytic Stability and Histopathological Effect.

Background and Objectives: One's quality of life depends on overall health, and in particular, oral health, which has been and continues to become a public health issue through frequent manifestations in various forms, from simple oral stomatitis (inflammations of the oral cavity) to the complicated oral health pathologies requiring medical interventions and treatments (caries, pulp necrosis and periodontitis). The aim of this study focused on the preparation and evaluation of vitamins (vitamin A, B1 and B6) incorporated into several silicone-based lining materials as a new alternative to therapeutically loaded materials designed as oral cavity lining materials in prosthodontics. Materials and Methods: Silicone-based liners containing vitamins were prepared by mixing them in solution and becoming crosslinked, and then they were characterized using Fourier-transform infrared (FT-IR) spectroscopy to confirm the incorporation of the vitamins into the silicone network; scanning electron microscopy (SEM) to evidence the morphology of the liner materials; dynamic vapor sorption (DVS) to evaluate their internal hydrophobicity, swelling in environments similar to biological fluids and mechanical test to demonstrate tensile strength; MTT to confirm their biocompatibility on normal cell cultures (fibroblast) and mucoadhesivity; and histopathological tests on porcine oral mucosa to highlight their potential utility as soft lining materials with improved efficiency. Results: FT-IR analysis confirmed the structural peculiarities of the prepared lining materials and the successful incorporation of vitamins into the silicone matrix. The surface roughness of the materials was lower than 0.2 µm, while in cross-section, the lining materials showed a compact morphology. It was found that the presence of vitamins induced a decrease in the main mechanical parameters (strength and elongation at break, Young's modulus) and hydrophobicity, which varied from one vitamin to another. A swelling degree higher than 8% was found in PBS 6.8 (artificial saliva) and water. Hydrolytic stability studies in an artificial saliva medium showed the release of low concentrations of silicone and vitamin fragments in the first 24 h, which increased the swelling behavior of the materials, diffusion and solubility of the vitamins. The microscopic images of fibroblast cells incubated with vitamin liners revealed very good biocompatibility. Also, the silicone liners incorporating the vitamins showed good mucoadhesive properties. The appearance of some pathological disorders with autolysis processes was more pronounced in the case of vitamin A liners. Conclusions: The addition of the vitamins was shown to have a beneficial effect that was mainly manifested as increased biocompatibility, hydrolytic stability and mucoadhesiveness with the mucosa of the oral cavity and less of an effect on the mechanical strength. The obtained lining materials showed good resistance in simulated biological media but caused a pronounced autolysis phenomenon, as revealed by histopathological examination, showing that these materials may have broad implications in the treatment of oral diseases.

Mucoadhesive Mesoporous Silica Particles as Versatile Carriers for Doxorubicin Delivery in Cancer Therapy.

Due to their structural, morphological, and behavioral characteristics (e.g., large volume and adjustable pore size, wide functionalization possibilities, excellent biocompatibility, stability, and controlled biodegradation, the ability to protect cargoes against premature release and unwanted degradation), mesoporous silica particles (MSPs) are emerging as a promising diagnostic and delivery platform with a key role in the development of next-generation theranostics, nanovaccines, and formulations. In this study, MSPs with customized characteristics in-lab prepared were fully characterized and used as carriers for doxorubicin (DOX). The drug loading capacity and the release profile were evaluated in media with different pH values, mimicking the body conditions. The release data were fitted to Higuchi, Korsmeyer-Peppas, and Peppas-Sahlin kinetic models to evaluate the release constant and the mechanism. The in vitro behavior of functionalized silica particles showed an enhanced cytotoxicity on human breast cancer (MCF-7) cells. Bio- and mucoadhesion on different substrates (synthetic cellulose membrane and porcine tissue mucosa)) and antimicrobial activity were successfully assessed, proving the ability of the OH- or the organically modified MSPs to act as antimicrobial and mucoadhesive platforms for drug delivery systems with synergistic effects.

Hybrid green bionanocomposites based on chitosan/starch/gelatin and metallic nanoparticles for biological applications.

Multicomponent composites based on natural biopolymers: chitosan, starch and gelatin in two different ratios (0.5:1:1 and 1:1:1) were in situ crosslinked by intermolecular interactions and used as matrices for zinc oxide and magnetite fillers. The bionanocomposite films have been evaluated by spectral and microscopy methods: Fourier-Transform Infrared spectrometry (FT-IR), Scanning Electron Microscopy (SEM) and Atomic Force Microscopy (AFM) confirming the electrostatic and hydrogen bonding interactions between the components of the polymeric matrices and the inorganic fillers and the crosslinking process. AFM and SEM images showed a compact, non-porous and homogenous morphology of the hybrid films, proving a good miscibility of the blends. At lower concentrations of embedded filler, the composites were less hardened and more ductile due to the interaction with the polymeric matrix. Increased amounts of inorganic NPs led to the reduced mechanical properties of the prepared materials and increased thermal stability. The bionanocomposites revealed a similar behavior of the dielectric constant with frequency and increased values at higher temperatures. The wettability of the films' surface and the values of the water sorption capacity revealed a slight hydrophilicity of the bionanocomposites as compared with the initial matrices. The biocompatibility, evaluated by means of the surface free energy components and the interfacial tension with blood, and the hemolysis analysis demonstrated that the bionanocomposites possess a low risk of thrombosis, being promising materials for in vivo biomedical applications.

Chemical Attachment of 5-Nitrosalicylaldimine Motif to Silatrane Resulting in an Organic-Inorganic Structure with High Medicinal Significance.

Two chemical motifs of interest for medicinal chemistry, silatrane as 1-(3-aminopropyl) silatrane (SIL M), and nitro group attached in position 5 to salicylaldehyde, are coupled in a new structure, 1-(3-{[(2-hydroxy-5-nitrophenyl)methylidene]amino}propyl)silatrane (SIL-BS), through an azomethine moiety, also known as a versatile pharmacophore. The high purity isolated compound was structurally characterized by an elemental, spectral, and single crystal X-ray diffraction analysis. Given the structural premises for being a biologically active compound, different specific techniques and protocols have been used to evaluate their in vitro hydrolytic stability in simulated physiological conditions, the cytotoxicity on two cancer cell lines (HepG2 and MCF7), and protein binding ability-with a major role in drug ADME (Absorption, Distribution, Metabolism and Excretion), in parallel with those of the SIL M. While the latter had a good biocompatibility, the nitro-silatrane derivative, SIL-BS, exhibited a higher cytotoxic activity on HepG2 and MCF7 cell lines, performance assigned, among others, to the known capacity of the nitro group to promote a specific cytotoxicity by a "activation by reduction" mechanism. Both compounds exhibited increased bio- and muco-adhesiveness, which can favor an optimized therapeutic effect by increased drug permeation and residence time in tumor location. Additional benefits of these compounds have been demonstrated by their antimicrobial activity on several fungi and bacteria species. Molecular docking computations on Human Serum Albumin (HSA) and MPRO COVID-19 protease demonstrated their potential in the development of new drugs for combined therapy.

Biocompatible Self-Assembled Hydrogen-Bonded Gels Based on Natural Deep Eutectic Solvents and Hydroxypropyl Cellulose with Strong Antimicrobial Activity.

Natural deep eutectic solvents (NADES)-hydroxypropyl cellulose (HPC) self-assembled gels with potential for pharmaceutical applications are prepared. FT-IR, 1HNMR, DSC, TGA and rheology measurements revealed that hydrogen bond acceptor−hydrogen bond donor interactions, concentration of NADES and the water content influence significantly the physico-chemical characteristics of the studied gel systems. HPC-NADES gel compositions have thermal stabilities lower than HPC and higher than NADES components. Thermal transitions reveal multiple glass transitions characteristic of phase separated systems. Flow curves evidence shear thinning (pseudoplastic) behavior. The flow curve shear stress vs. shear rate were assessed by applying Bingham, Herschel−Bulkley, Vocadlo and Casson rheological models. The proposed correlations are in good agreement with experimental data. The studied gels evidence thermothickening behavior due to characteristic LCST (lower critical solution temperature) behavior of HPC in aqueous systems and a good biocompatibility with normal cells (human gingival fibroblasts). The order of antibacterial and antifungal activities (S.aureus, E.coli, P. aeruginosa and C. albicans) is as follows: citric acid >lactic acid > urea > glycerol, revealing the higher antibacterial and antifungal activities of acids.

Hydroxypropyl Cellulose/Pluronic-Based Composite Hydrogels as Biodegradable Mucoadhesive Scaffolds for Tissue Engineering.

Recently, the development of new materials with the desired characteristics for functional tissue engineering, ensuring tissue architecture and supporting cellular growth, has gained significant attention. Hydrogels, which possess similar properties to natural cellular matrixes, being able to repair or replace biological tissues and support the healing process through cellular proliferation and viability, are a challenge when designing tissue scaffolds. This paper provides new insights into hydrogel-based polymeric blends (hydroxypropyl cellulose/Pluronic F68), aiming to evaluate the contributions of both components in the development of new tissue scaffolds. In order to study the interactions within the hydrogel blends, FTIR and 1HNMR spectroscopies were used. The porosity and the behavior in moisture medium were highlighted by SEM and DVS analyses. The biodegradability of the hydrogel blends was studied in a simulated biological medium. The hydrogel composition was determinant for the scaffold behavior: the HPC component was found to have a great influence on the BET and GAB areas, on the monolayer values estimated from sorption-desorption isotherms and on mucoadhesivity on small intestine mucosa, while the Pluronic F68 component improved the thermal stability. All blends were also found to have good mechanical strength and increased biocompatibility on the NHDF cell line. Based on their particular compositions and increased mucoadhesivity on small intestine mucosa, these polymeric blends could be effective in the repair or recovery of damaged cell membranes (due to the contribution of Pluronic F68) or in control drug-delivery intestinal formulations.

Mucoadhesive and Antimicrobial Allantoin/ß Cyclodextrins-Loaded Carbopol Gels as Scaffolds for Regenerative Medicine.

Allantoin and its ß-cyclodextrin and hydroxypropyl-ß-cyclodextrin inclusion complexes 1:1 have been used to prepare carbopol-based mucoadhesive gels. The gelation process occurred by adjustment with glycerol 10% in the presence of triethanolamine. The structural features induced by the presence of allantoin and the corresponding ß-cyclodextrins inclusion complexes have been first investigated by infrared spectroscopy highlighting strong interactions within the gels network and ideal crosslinks for the self-healing behavior. The hydrophilicity of the gels was investigated by the determination of the surface tension parameters and the free energy of hydration. The interfacial free energy values indicated prolonged biocompatibility with blood. The gels-water molecule interactions in terms of sorption, permeability, and diffusion coefficients were evaluated by dynamic vapor sorption analysis. The self-assembly process through intermolecular H-bonding, the high hydrophilicity, the mechanical performance, the hydrolytic stability in simulated biological media, the biocompatibility with normal human dermal fibroblast (NHDF) cells, the mucoadhesivity and antimicrobial activity on selected microorganism species (S. Aureus and C. albicans) of the allantoin-based gels recommend them as promising scaffold alternatives in regenerative medicine.

Functionalized Mesoporous Silica as Doxorubicin Carriers and Cytotoxicity Boosters.

Mesoporous silica nanoparticles (MSNs) bearing methyl, thiol or glucose groups were synthesized, and their encapsulation and release behaviors for the anticancer drug Doxorubicin (Dox) were investigated in comparison with nonporous homologous materials. The chemical modification of thiol-functional silica with a double bond glucoside was completed for the first time, by green thiol-ene photoaddition. The MSNs were characterized in terms of structure (FT-IR, Raman), morphology (TEM), porosity (nitrogen sorption-desorption) and Zeta potential measurements. The physical interactions responsible for the Dox encapsulation were investigated by analytic methods and MD simulations, and were correlated with the high loading efficiency of MSNs with thiol and glucose groups. High release at pH 5 was observed in most cases, with thiol-MSN exhibiting 98.25% cumulative release in sustained profile. At pH 7.4, the glucose-MSN showed 75.4% cumulative release, while the methyl-MSN exhibited a sustained release trend. The in vitro cytotoxicity was evaluated on NDHF, MeWo and HeLa cell lines by CellTiter-Glo assay, revealing strong cytotoxic effects in all of the loaded silica at low equivalent Dox concentration and selectivity for cancer cells. Atypical applications of each MSN as intravaginal, topical or oral Dox administration route could be proposed.

MWCNTs Composites-Based on New Chemically Modified Polysulfone Matrix for Biomedical Applications.

Polyvinyl alcohol (PVA) is a non-toxic biosynthetic polymer. Due to the hydrophilic properties of the PVA, its utilization is an easy tool to modify the properties of materials inducing increased hydrophilicity, which can be noticed in the surface properties of the materials, such as wettability. Based on this motivation, we proposed to obtain high-performance composite materials by a facile synthetic method that involves the cross-linking process of polyvinyl alcohol (PVA) with and aldehyde-functionalized polysulfone(mPSF) precursor, prior to incorporation of modified MWCNTs with hydrophilic groups, thus ensuring a high compatibility between the polymeric and the filler components. Materials prepared in this way have been compared with those based on polyvinyl alcohol and same fillers (mMWCNTs) in order to establish the influence of the polymeric matrix on the composites properties. The amount of mMWCNTs varied in both polymeric matrices between 0.5 and 5 wt%. Fourier transformed infrared with attenuated total reflectance spectroscopy (FTIR-ATR) was employed to confirm the changes noted in the PVA, mPSF and their composites. Hemolysis degree was investigated in correlation with the material structural features. Homogenous distribution of mMWCNTs in all the composite materials has been confirmed by scanning electron microscopy. The hydrophilicity of both composite systems, estimated by the contact angle method, was influenced by the presence of the filler amount mMWCNTs in both matrices (PVA and mPSF). Our work demonstrates that mPSF/mMWCNTs and PVA/mMWCNTs composite could be used as water purification or blood-filtration materials.

From Amorphous Silicones to Si-Containing Highly Ordered Polymers: Some Romanian Contributions in the Field.

Polydimethylsiloxane (PDMS), in spite of its well-defined helical structure, is an amorphous fluid even at extremely high molecular weights. The cause of this behavior is the high flexibility of the siloxane backbone and the lack of intermolecular interactions attributed to the presence of methyl groups. These make PDMS incompatible with almost any organic or inorganic component leading to phase separation in siloxane-siloxane copolymers containing blocks with polar organic groups and in siloxane-organic copolymers, where dimethylsiloxane segments co-exist with organic ones. Self-assembly at the micro- or nanometric scale is common in certain mixed structures, including micelles, vesicles, et cetera, manifesting reversibly in response to an external stimulus. Polymers with a very high degree of ordering in the form of high-quality crystals were obtained when siloxane/silane segments co-exist with coordinated metal blocks in the polymer chain. While in the case of coordination of secondary building units (SBUs) with siloxane ligands 1D chains are formed; when coordination is achieved in the presence of a mixture of ligands, siloxane and organic, 2D structures are formed in most cases. The Romanian research group's results regarding these aspects are reviewed: from the synthesis of classic, amorphous silicone products, to their adaptation for use in emerging fields and to new self-assembled or highly ordered structures with properties that create perspectives for the use of silicones in hitherto unexpected areas.

Blends of sodium deoxycholate-based poly(ester ether)urethane ionomer and hydroxypropylcellulose with mucosal adhesiveness.

New mucoadhesive blends of sodium deoxycholate-based poly(ester ether)urethane ionomer (PU) and hydroxypropyl cellulose (HPC) are prepared. The presence of the intermolecular interactions between the polymeric components has been investigated by FTIR spectroscopy indicating their miscibility in the solid phase. DSC studies also revealed a single glass transition of the blends, which is indicative of miscibility of PU and HPC in the amorphous phase. The amount of HPC in the blends influences strongly the physicochemical and mucoadhesion/bioadhesion properties. It was found that the value of area attributed to ordered hydrogen bonding (FTIR), the onset temperature values of thermal degradation in N2 flow (TG/DTG), the values of the sorption capacity (Dynamic Vapor Sorption-DVS), the values of the apparent viscosity (rheological measurements) and mucoadhesion/bioadhesion properties increased by increasing the HPC content in the blends. Complex viscosity revealed shear thinning behavior for all the studied solutions evidencing the contributive role of polymer viscoelasticity on mucoadhesion. It was found that both G' and G" increase with an increase in angular frequency and G">G' which is characteristic for liquid-like (sol state) behavior for all blended solutions and this behavior is helpful in the adhesion with mucosa surface. Mucoadhesion of PU/HPC blends was assessed in the stomach mucosa at pH 2.6 and 37 °C. Bioadhesion test was performed at pH 7.4 and 37 °C and revealed a stronger interaction of PU/HPC blends with cellulose membrane than with stomach mucosa. The similar nature of the HPC and cellulose membrane determines additional adhesion forces and implicity high adhesion properties. The HPC component increases the hydrophilicity of the blends as DVS analysis revealed, but also leads to hydrolytic degradation. FTIR spectroscopy analysis was used to evaluate the hydrolytic stability in acid (pH 2.6) and slightly alkaline (pH 7.4) PBS media and a mechanism of degradation has been proposed.

Photo-oxidative degradation of doxorubicin with siloxane MOFs by exposure to daylight.

Doxorubicin (DOX) is a chemotherapeutic agent from anthracycline class, which acts unselectively on all cells; thus, it may have genotoxic and/or mutagenic effects and cause serious environmental problems. Herein, the decomposition of a diluted solution of DOX hydrochloride for injection has been investigated under photo-oxidative conditions, in ambient light and without pH modification, using hydrogen peroxide as oxidizing agent and hydrophobic siloxane-based metal-organic frameworks (MOFs) as heterogeneous catalysts. The kinetics of the photodegradation process was followed by UV-Vis spectroscopy and by ESI-MS. According to UV-Vis data, two pseudo-first-order kinetic steps describe the process, with rate constants in the order of 10-3-10-2 min-1 for the rate-determining one. ESI-MS provided more accurate information, with a rate constant of 2.6 · 10-2 min-1 calculated from the variation of DOX ion abundance. Complete decomposition of DOX was achieved after 120 min in the shade and after only 20 min by exposure to sunlight. The analysis of the residual waters by mass spectrometry and 1D and 2D NMR spectroscopy showed complete disappearance of DOX in all cases, excluded any anthracycline species, which are destroyed in the tested conditions, and proved formation of an un-harmful compound-glycerol, while no trace of metal was detected by XRF. Preliminary data also showed decomposition of oxytetracycline in similar conditions. By this study, we bring into attention a less-addressed pollution issue and we propose a mild and effective method for the removal of drug emerging pollutants.

X-ray Structure Elucidation of a Pt-Metalloporphyrin and Its Application for Obtaining Sensitive AuNPs-Plasmonic Hybrids Capable of Detecting Triiodide Anions.

The development of UV⁻vis spectrophotometric methods based on metalloporphyrins for fast, highly sensitive and selective anion detection, which avoids several of the practical challenges associated with other detection methods, is of tremendous importance in analytical chemistry. In this study, we focused on achieving a selective optical sensor for triiodide ion detection in traces based on a novel hybrid material comprised of Pt(II) 5,10,15,20-tetra(4-methoxy-phenyl)-porphyrin (PtTMeOPP) and gold nanoparticles (AuNPs). This sensor has high relevance in medical physiological tests. The structure of PtTMeOPP was investigated by single crystal X-ray diffraction in order to understand the metal surroundings and the molecule conformation and to assess if it qualifies as a potential sensitive material. It was proven that the Pt-porphyrin generated 1D H-bond supramolecular chains due to the weak C-H···O intermolecular hydrogen bonding. The presence of ordered voids in the crystal encouraged us to use PtTMeOPP as the sensing material for triiodide ion and to enhance its potential in a novel AuNPs/PtTMeOPP hybrid by the synergistic effects provided by the plasmonic gold nanoparticles. The spectrophotometric sensor is characterized by a detection limit of 1.5 × 10-9 M triiodide ion concentration and a remarkable confidence coefficient of 99.98%.

Development of New Bexarotene-loaded Mesoporous Silica Systems for Topical Pharmaceutical Formulations.

The present study reports the first time use of MCM-41 mesoporous silica as highly efficient carrier for bexarotene - an antineoplastic agent specific for cutaneous T-cell lymphoma treatment. Bexarotene is highly toxic and poor-water soluble, having low bioavailability in the conventional pharmaceutical forms. Comparative uptake of bexarotene on amino-functionalized silica host at various functionalization degrees is discussed in details taking into account all structural features, of matrix as well as properties of the drug molecules. The obtained results proved a successful bexarotene loading on amino-functionalized MCM-41 silica. The bexarotene molecules are adsorbed on the active centers in non-crystalline state proving the major role of the silica amino-functionalization for the drug solubility and bioavailability enhancing. In vitro dissolution tests showed a prolonged release of bexarotene during 12 h, reaching 50% release of loaded active molecules. The prolonged release has been demonstrated to be a result of the presence of aminopropyl groups on the silica pore walls.

Assessment of chemicals released in the marine environment by dielectric elastomers useful as active elements in wave energy harvesters.

A series of elastomers, either natural or synthetic (some of them commercial, while others prepared in the laboratory), suitable for use as active elements in devices for wave energy harvesting, were evaluated concerning their behavior and effects on the marine environment. In this aim, the elastomer films, initially evaluated regarding their aspect, structure, surface wettability, and tolerance of microorganisms growth, were immersed in synthetic seawater (SSW) within six months for assessing compounds released. There were analyzed the changes occurred both in the elastomers and salt water in which they were immersed. For this, water samples taken at set time intervals were analyzed by using a sequence of sensitive spectral techniques: UV-vis, IR, and in relevant cases 1H NMR and electrospray ionization mass spectrometry (ESI-MS), able to detect and identify organic compounds, while after six months, they were also investigated from the point of view of aspect, presence of metal traces, pH, and biological activity. The changes in aspect, structure and morphology of the dielectric films at the end of the dipping period were also evaluated by visual inspection, IR spectroscopy by using spectral subtraction method, and SEM-EDX technique.

Design, Preparation and Evaluation of HPMC-Based PAA or SA Freeze-Dried Scaffolds for Vaginal Delivery of Fluconazole.

PURPOSE: Aim of this work was preparation of bioadhesive gel formulations based on Hydroxypropyl methylcellulose (HPMC), Poly(acrylic acid) (PAA) or Sodium alginate (SA) loaded with anise/fluconazole ß-cyclodextrin inclusion complexes in 1:2 and 1:3 ratios intended for vaginal applications. METHODS: Freeze-drying method was effectively utilized and superporous morphology was obtained. The superporous morphology of the lyophilized gels, dynamic water vapor sorption measurements, drug release kinetics studies and their antimicrobial activities are presented. RESULTS: HPMC content influences especially the sorption/desorption behaviour of HPMC-based PAA gels and the morphology of the gel formulations with fluconazole/ß-cyclodextrin inclusion complexes, due to the interactions among the gel networks absorbing water molecules. It was found that fluconazole release kinetics correspond to quasi-Fickian, Fickian diffusion and non-Fickian mechanisms for the studied hydrogels. The tested vaginal formulations with ß-cyclodextrin inclusion complexes exhibited selectivity toward S. aureus ATCC 25923 and all tested Candida strains in comparison with the gel formulation without ß-cyclodextrin. CONCLUSIONS: The fluconazole/ß cyclodextrin inclusion complexes ensure a controlled release of fluconazole over a few days, the highest amount of drug release (92%) being observed after 43 h. These bioadhesive gel formulations could be very promising topical alternative for treatment of vaginal fungal infections.