Poly(ethylene glycol) Methyl Ether Acrylate-Grafted Chitosan-Based Micro- and Nanoparticles as a Drug Delivery System for Antibiotics.

Nanotechnology is the science of creating materials at the nanoscale by using various devices, structures, and systems that are often inspired by nature. Micro- and nanoparticles (MPs, NPs) are examples of such materials that have unique properties and can be used as carriers for delivering drugs for different biomedical applications. Chitosan (CS) is a natural polysaccharide that has been widely studied, but it has a problem with low water solubility at neutral or basic pH, which limits its processability. The goal of this work was to use a chemically modified CS with poly(ethylene glycol) methyl ether acrylate (PEGA) to prepare CS micronic and submicronic particles (MPs/NPs) that can deliver different types of antibiotics, respectively, levofloxacin (LEV) and Ciprofloxacin (CIP). The particle preparation procedure employed a double crosslinking method, ionic followed by a covalent, in a water/oil emulsion. The studied process parameters were the precursor concentration, stirring speeds, and amount of ionic crosslinking agent. MPs/NPs were characterized by FT-IR, SEM, light scattering granulometry, and Zeta potential. MPs/NPs were also tested for their water uptake capacity in acidic and neutral pH conditions, and the results showed that they had a pH-dependent behavior. The MPs/NPs were then used to encapsulate two separate drugs, LEV and CIP, and they showed excellent drug loading and release capacity. The MPs/NPs were also found to be safe for cells and blood, which demonstrated their potential as suitable drug delivery systems for biomedical applications.

Development and Digital Light Processing 3D Printing of a Vitrimer Composed of Glycerol 1,3-Diglycerolate Diacrylate and Tetrahydrofurfuryl Methacrylate.

The development of biobased reshapable and repairable vitrimers has received extensive attention due to the growing focus on an environmentally friendly society. Therefore, the objective of this research was to synthesize sustainable polymers with an environmentally friendly strategy combining the benefits of renewable resources, UV curing, and vitrimers. Two biobased monomers, glycerol 1,3-diglycerolate diacrylate and tetrahydrofurfuryl methacrylate, were chosen for the preparation of UV-curable resins and tested by real-time photorheometry and RT-FTIR spectroscopy to determine their suitability for digital light processing (DLP) 3D printing. DLP 3D-printed polymer showed shape memory, weldability, and repairability capabilities by triggering the dynamic transesterification process at high temperatures. The vitrimer with a weight ratio of 60:40 of glycerol 1,3-diglycerolate diacrylate and tetrahydrofurfuryl methacrylate showed shape memory properties with a recovery ratio of 100% and a 7-fold improved tensile strength compared to the original sample, confirming efficient weldability and repairability.

Influence of Block-Copolymers' Composition as Compatibilizers for Epoxy/Silicone Blends.

The objective of this study was to prepare crosslinked epoxy networks containing liquid silicone particles in order to improve their mechanical properties and obtain less brittle materials. Different copolymers were used as compatibilizers. These copolymers vary in their chemical composition and structure. All of the copolymers contain hydrophobic (PDMS sequences) and hydrophilic groups. The effect of their chemical structure and architecture on the morphology of the dispersed phase, and on the final physico-chemical and flexural characteristics of epoxy/silicone blends, was explored. The morphology of crosslinked formulations was studied by scanning electron microscopy (SEM), and the thermal characteristics (glass transition temperature, Tg, and curing exothermic peak) were determined by differential scanning calorimetry (DSC). The experimental results have shown that the average diameter and particle size distribution of silicone particles depend on the chemical structure and architecture of the compatibilizers. One copolymer has been identified as the best compatibilizer, allowing a lower mean diameter and particle size distribution in addition to the best mechanical properties of the final network (less brittle character). This study has consequently evidenced the possibility of creating in situ silicone capsules inside an epoxy network by adding tailored compatibilizers to epoxy/silicone formulations.

In situ preparation of compounds using silanized mPEG inspired by talc-like structures.

Composite materials show improved properties compared to pristine materials, in particular when the filler is dispersed homogeneously in the matrix. For polymer-clay composites, different strategies exist to improve clay mineral dispersion in the polymer matrix. In this study, an innovative approach is suggested which consists of forming a talc-like structure directly in a polymer matrix using a silanized polymer as the silicon source. Poly(ethylene glycol) methyl ether of different average molar masses (Mn = 350, 500, 750, 1900 g mol-1) were functionalized with (3-isocyanatopropyl)triethoxysilane and added to the ethanolic solutions of magnesium nitrate. 1H-29Si CPMAS solid state NMR experiments revealed partial condensation of silane compounds, and FTIR analysis confirmed the presence of both Si-O and Mg-O bonds, but an additional proof of the Si-O-Mg bond is needed to prove the formation of such a structure.

Design of Potent Inhibitors Targeting the Main Protease of SARS-CoV-2 Using QSAR Modeling, Molecular Docking, and Molecular Dynamics Simulations.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a serious global public health threat. The evolving strains of SARS-CoV-2 have reduced the effectiveness of vaccines. Therefore, antiviral drugs against SARS-CoV-2 are urgently needed. The main protease (Mpro) of SARS-CoV-2 is an extremely potent target due to its pivotal role in virus replication and low susceptibility to mutation. In the present study, a quantitative structure-activity relationship (QSAR) study was performed to design new molecules that might have higher inhibitory activity against SARS-CoV-2 Mpro. In this context, a set of 55 dihydrophenanthrene derivatives was used to build two 2D-QSAR models using the Monte Carlo optimization method and the Genetic Algorithm Multi-Linear Regression (GA-MLR) method. From the CORAL QSAR model outputs, the promoters responsible for the increase/decrease in inhibitory activity were extracted and interpreted. The promoters responsible for an increase in activity were added to the lead compound to design new molecules. The GA-MLR QSAR model was used to ensure the inhibitory activity of the designed molecules. For further validation, the designed molecules were subjected to molecular docking analysis and molecular dynamics simulations along with an absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis. The results of this study suggest that the newly designed molecules have the potential to be developed as effective drugs against SARS-CoV-2.

A bionanocomposite of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate)/ZnO-nanoparticles intended for food packaging.

Films-based bionanocomposites have gained a great importance in food plastic packaging because they are eco-friendly materials and have the potential to improve food protection, while limiting the accumulation of synthetic plastics on the planet. In this paper, biofilms were prepared using poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) reinforced with Zinc oxide nanoparticles (ZnO-NPs) to develop new bionanocomposite materials intended for food packaging. The samples were fabricated using first solvent casting method followed by melt compounding at various loading rates, i.e., 1.5, 3 and 6 wt%. The obtained results showed that the incorporation of ZnO-NPs to PHBHHx at 3 wt% leads to higher crystallinity, improved mechanical properties and antimicrobial activity, compared with neat polymer and other bionanocomposites. This was attributed to the finer and homogeneous nanofiller dispersion in the polymer matrix evidenced by scanning electron microscopy analysis. Whereas at 6 wt%, the bionanocomposite sample exhibited low mechanical properties due to the formation of ZnO-NPs aggregates. In view of the obtained results, the study highlights the potential of using the PHBHHx/ZnO-NPs bionanocomposite at 3 wt% in food packaging without any prior filler treatment.

Biodegradability Assessment of Polyester Copolymers Based on Poly(ethylene adipate) and Poly(ε-caprolactone).

Biodegradable polymers contain chains that are hydrolytically or enzymatically cleaved, resulting in soluble degradation products. Biodegradability is particularly desired in biomedical applications, in which degradation of the polymer ensures clearance from the body and eliminates the need for retrieval or explant. In this study, a homologues series of poly(ε-caprolactone)-b-poly(ethylene adipate)-b-poly(ε-caprolactone) (PCL-b-PEA-b-PCL) block copolymers, with constant PEA molar mass and different PCL sequence lengths was obtained. The starting point of these copolymers was a dihydroxy-PEA precursor with a molar mass (Mn) of 2500 g/mol. Mn values of the PCL varied between 1000 and 10,000 g/mol. Both the precursors and the copolymers were characterized using different physicochemical methods, such as: NMR, SEC, Maldi-TOFF, DSC, and ATG. The molecular characteristics of the copolymers were in a direct correlation with the sequence length of the PCL. Enzymatic degradability studies were also conducted by using cell-free extract containing Pseudomonas aeruginosa PAO1 for 10 and 21 days, and it appeared that the presence of the PEA central sequence has an important influence on the biodegradability of the copolymer samples. In fact, copolymer PCL7000-PEA2500-PCL7000 had a weight loss of around 50% after 10 days whereas the weight loss of the homopolymer PCL, with a similar Mn of 14,000 g/mol, was only 6%. The results obtained in this study indicate that these copolymer samples can be further used for the preparation of drug delivery systems with modulated biodegradability.

Chitosan Grafted Poly (Ethylene Glycol) Methyl Ether Acrylate Particulate Hydrogels for Drug Delivery Applications.

Chitosan (CS) crosslinking has been thoroughly investigated, but the chemical reactions leading to submicronic hydrogel formulations pose problems due to various physical/chemical interactions that limit chitosan processability. The current study employs the chemical modification of chitosan by Michael addition of poly (ethylene glycol) methyl ether acrylate (PEGA) to the amine groups to further prepare chitosan particulate hydrogels (CPH). Thus, modified CS is subjected to a double crosslinking, ionic and covalent, in water/oil emulsion. The studied process parameters are polymer concentration, stirring speed, and quantity of ionic crosslinker. The CPH were structurally and morphologically characterized through infrared spectroscopy, scanning electron microscopy, light scattering granulometry, and zeta potential, showing that modified CS allows better control of dimensional properties and morphology as compared with neat CS. Swelling properties were studied in acidic and neutral pH conditions, showing that pH-dependent behavior was maintained after grafting and double crosslinking. The applicability of the prepared materials was further tested for drug loading and in vitro delivery of levofloxacin (LEV), showing excellent capacity. CPH were found to be cyto- and hemocompatible demonstrating their potential for effective use as a controlled release system for different biomedical applications.

Drug-Loaded Polymeric Micelles Based on Smart Biocompatible Graft Copolymers with Potential Applications for the Treatment of Glaucoma.

Glaucoma is the second leading cause of blindness in the world. Despite the fact that many treatments are currently available for eye diseases, the key issue that arises is the administration of drugs for long periods of time and the increased risk of inflammation, but also the high cost of eye surgery. Consequently, numerous daily administrations are required, which reduce patient compliance, and even in these conditions, the treatment of eye disease is too ineffective. Micellar polymers are core-shell nanoparticles formed by the self-assembly of block or graft copolymers in selective solvents. In the present study, polymeric micelles (PMs) were obtained by dialysis from smart biocompatible poly(ε-caprolactone)-poly(N-vinylcaprolactam-co-N-vinylpyrrolidone) [PCL-g-P(NVCL-co-NVP)] graft copolymers. Two copolymers with different molar masses were studied, and a good correlation was noted between the micellar sizes and the total degree of polymerisation (DPn) of the copolymers. The micelles formed by Cop A [PCL120-g-P(NVCL507-co-NVP128)], with the lowest total DPn, have a Z-average value of 39 nm, whereas the micellar sizes for Cop B [PCL120-g-P(NVCL1253-co-NVP139)] are around 47 nm. These PMs were further used for the encapsulation of two drugs with applications for the treatment of eye diseases. After the encapsulation of Dorzolamide, a slight increase in micellar sizes was noted, whereas the encapsulation of Indomethacin led to a decrease in these sizes. Using dynamic light scattering, it was proved that both free and drug-loaded PMs are stable for 30 days of storage at 4 °C. Moreover, in vitro biological tests demonstrated that the obtained PMs are both haemo- and cytocompatible and thus can be used for further in vivo tests. The designed micellar system proved its ability to release the encapsulated drugs in vitro, and the results obtained were validated by in vivo tests carried out on experimental animals, which proved its high effectiveness in reducing intraocular pressure.

Chitosan grafted-poly(ethylene glycol) methacrylate nanoparticles as carrier for controlled release of bevacizumab.

The aim of the present study is to obtain, for the first time, polymeric nanocarriers based on the chitosan grafted-poly(ethylene glycol) methacrylate derivative. The strategy involves the use of chitosan grafted-poly(ethylene glycol) methacrylate with high solubility in water, obtained via Michael addition, in order to prepare potentially non-toxic micro/nanoparticles (MNPs). By modifying chitosan, its solubility in aqueous media was improved. Micro/nanoparticles-based chitosan grafted-poly(ethylene glycol) methacrylate were obtained under mild condition, with good and controlled swelling properties in acetate buffer solution (ABS) and phosphate buffer solution (PBS). The technique selected for the preparation of the MNPs was a double crosslinking (ionic and covalent) process in reverse emulsion which provide the mechanical stability of the polymeric nanocarrier. The chitosan derivative and MNPs were thoroughly characterized by Fourier Transform Infrared Spectroscopy (FT-IR), Thermogravimetric Analysis (TGA), Differential Scanning Calorimetry (DSC), Scanning Electron Microscopy (SEM). The Scanning Electron Microscopy photographs revealed that prepared MNPs have different diameters depending on the used stirring rate and polymer concentration. Nanoparticles potential as drug delivery system was analyzed by loading bevacizumab (BEV) a full-length monoclonal antibody. Also, the prepared particles were found suitable from the cytotoxicity and hemocompatibility point of view enabling their potential use as delivery system for the treatment of posterior segment of the eye conditions.

A new synthetic pathway based on one-pot sequential aza-Michael addition and photoCuAAC click reactions.

A solvent-free process is described for the synthesis of tailor-made molecules from a one-pot, two-step approach combining aza-Michael addition and photoinduced copper(i) catalysed azide-alkyne (photo-CuAAC) reactions. After the first reaction between an amine and an acrylate, cycloaddition between an azide and an alkyne is activated by light irradiation in the presence of a copper complex. The kinetics of the aza-Michael addition and photo-CuAAC reaction were investigated by liquid state 1H NMR spectroscopy and real-time Fourier transform infrared spectroscopy. This new process represents a well-defined spatio-temporal pathway to the synthesis of bespoke intermediate molecules for various applications.

Investigation on the adsorption of alkoxysilanes on stainless steel.

Alkoxysilanes, and mainly trialkoxysilanes, have been widely used as coupling agents on metallic surfaces. They are of interest mainly because they form a water-stable covalent bond with a surface composed of hydroxides. The grafting of these molecules should also give rise to the formation of a siloxane network at the substrate's surface. However, only a few studies examine stainless steel substrate, such as AISI 316L, for which the main difficulty is the low surface reactivity. In order to improve the silane anchoring, a prehydrolysis of the alkoxysilane was performed to transform the methoxy groups into silanol groups. This reaction happened in an aqueous medium and at a controlled pH, which impacted the prehydrolysis efficiency. Curing followed this step, which allows the grafting of the alkoxysilane on stainless steel's surface. Polarization modulation infrared reflection absorption spectroscopy (PM-IRRAS) was performed in order to identify the grafting of the silane molecules. Tests were made to compare the grafting of alkoxysilanes as a function of their functional groups and their prehydrolysis conditions. PM-IRRAS coupled with atomic force microscopy allowed the observation of the grafting of the studied alkoxysilanes. The nature of the remaining functional group (its ability to react with polymer, for example) of the alkoxysilane plays a major role in this process, since its chemical nature influences the grafting mechanism.

Maghemite Intercalated Montmorillonite as New Nanofillers for Photopolymers.

In this work, maghemite intercalated montmorillonite (γFe2O3-MMT)/polymer nanocomposites loaded with 1 or 2 wt.% of nanofillers were obtained by photopolymerization of difunctional acrylate monomers. The γFe2O3-MMT nanofillers were prepared by a new method based on the in situ formation of maghemite in the interlayer space of Fe-MMT using a three step process. X-ray diffraction (XRD), chemical analysis, TG/DTA and transmission electron microscopy (TEM) characterization of these nanofillers indicated the efficiency of the synthesis. When following the kinetics of the photopolymerization of diacrylate-γFe2O3-MMT nanocomposites using FTIR spectroscopy no significant inhibition effect of the nanofillers was observed at a loading up to 2 wt.%. These innovative nanocomposites exhibit improved mechanical properties compared to the crude polymer.

FTIR study of polycaprolactone chain organization at interfaces.

Polycaprolactone (PCL), extensively known as a biomaterial, is the subject of this paper. Knowing well that some biomaterial applications exhibit specific chain organization, we focused our study on the orientation of PCL chains when this polymer is adsorbed (spin-coated) on inert substrates such as gold-coated glass slides. The main technique allowing adsorbed thin films analysis that we chose is polarization-modulation infrared reflection-absorption spectroscopy (PM-IRRAS), which permits qualitative and quantitative determination of chain anisotropy in the confined layers at the interface. Based on our spectroscopic results, we achieved an adsorption model of PCL chains and we calculated orientation angles with respect to the substrate normal. Calculated values show a quasi-perpendicular deposition of PCL chains on the gold substrate. Moreover, PCL thin films remain highly crystalline, a fact which could be the basis of the important anisotropy of PCL chains.