Fluorine-Containing Block and Gradient Copoly(2-oxazoline)s Based on 2-(3,3,3-Trifluoropropyl)-2-oxazoline: A Quest for the Optimal Self-Assembled Structure for 19F Imaging.

The use of fluorinated contrast agents in magnetic resonance imaging (MRI) facilitates improved image quality due to the negligible amount of endogenous fluorine atoms in the body. In this work, we present a comprehensive study of the influence of the amphiphilic polymer structure and composition on its applicability as contrast agents in 19F MRI. Three series of novel fluorine-containing poly(2-oxazoline) copolymers and terpolymers, hydrophilic-fluorophilic, hydrophilic-lipophilic-fluorophilic, and hydrophilic-thermoresponsive-fluorophilic, with block and gradient distributions of the fluorinated units, were synthesized. It was discovered that the CF3 in the 2-(3,3,3-trifluoropropyl)-2-oxazoline (CF3EtOx) group activated the cationic chain end, leading to faster copolymerization kinetics, whereby spontaneous monomer gradients were formed with accelerated incorporation of 2-methyl-2-oxazoline or 2-n-propyl-2-oxazoline with a gradual change to the less-nucleophilic CF3EtOx monomer. The obtained amphiphilic copolymers and terpolymers form spherical or wormlike micelles in water, which was confirmed using transmission electron microscopy (TEM), while small-angle X-ray scattering (SAXS) revealed the core-shell or core-double-shell morphologies of these nanoparticles. The core and shell sizes obey the scaling laws for starlike micelles predicted by the scaling theory. Biocompatibility studies confirm that all copolymers obtained are noncytotoxic and, at the same time, exhibit high sensitivity during in vitro 19F MRI studies. The gradient copolymers provide the best 19F MRI signal-to-noise ratio in comparison with the analogue block copolymer structures, making them most promising as 19F MRI contrast agents.

Reconstructing Reliable Powder Patterns from Spikelets (Q)CPMG NMR Spectra: Simplification of UWNMR Crystallography Analysis.

Spikelets NMR spectra are very popular as they enable the shortening of experimental time and give the possibility to obtain required NMR parameters for nuclei with ultrawide NMR patterns. Unfortunately, these resulted ssNMR spectra cannot be fitted directly in common software. For this reason, we developed UWNMRSpectralShape (USS) software which transforms spikelets NMR patterns into single continuous lines. Subsequently, these reconstructed spectral envelopes of the (Q)CPMG spikelets patterns can be loaded into common NMR software and automatically fitted, independently of experimental settings. This allows the quadrupole and chemical shift parameters to be accurately determined. Moreover, it makes fitting of spikelets NMR spectra exact, fast and straightforward.

High-Affinity N-(2-Hydroxypropyl)methacrylamide Copolymers with Tailored N-Acetyllactosamine Presentation Discriminate between Galectins.

N-Acetyllactosamine (LacNAc; Galß4GlcNAc) is a typical disaccharide ligand of galectins. The most abundant members of these human lectins, galectin-1 (Gal-1) and galectin-3 (Gal-3), participate in a number of pathologies including cancerogenesis and metastatic formation. In this study, we synthesized a series of fifteen N-(2-hydroxypropyl)methacrylamide (HPMA)-based glycopolymers with varying LacNAc amounts and presentations and evaluated the impact of their architecture on the binding affinity to Gal-1 and Gal-3. The controlled radical reversible addition-fragmentation chain transfer copolymerization technique afforded linear polymer precursors with comparable molecular weight (Mn ≈ 22,000 g mol-1) and narrow dispersity (D̵ ≈ 1.1). The precursors were conjugated with the functionalized LacNAc disaccharide (4-22 mol % content in glycopolymer) prepared by enzymatic synthesis under catalysis by ß-galactosidase from Bacillus circulans. The structure-affinity relationship study based on the enzyme-linked immunosorbent assay revealed that the type of LacNAc presentation, individual or clustered on bi- or trivalent linkers, brings a clear discrimination (almost 300-fold) between Gal-1 and Gal-3, reaching avidity to Gal-1 in the nanomolar range. Whereas Gal-1 strongly preferred a dense presentation of individually distributed LacNAc epitopes, Gal-3 preferred a clustered LacNAc presentation. Such a strong galectin preference based just on the structure of a multivalent glycopolymer type is exceptional. The prepared nontoxic, nonimmunogenic, and biocompatible glycopolymers are prospective for therapeutic applications requiring selectivity for one particular galectin.

Reactive Oxygen Species (ROS)-Responsive Polymersomes with Site-Specific Chemotherapeutic Delivery into Tumors via Spacer Design Chemistry.

The lack of cellular and tissue specificities in conventional chemotherapies along with the generation of a complex tumor microenvironment (TME) limits the dosage of active agents that reaches tumor sites, thereby resulting in ineffective responses and side effects. Therefore, the development of selective TME-responsive nanomedicines is of due relevance toward successful chemotherapies, albeit challenging. In this framework, we have synthesized novel, ready-to-use ROS-responsive amphiphilic block copolymers (BCs) with two different spacer chemistry designs to connect a hydrophobic boronic ester-based ROS sensor to the polymer backbone. Hydrodynamic flow focusing nanoprecipitation microfluidics (MF) was used in the preparation of well-defined ROS-responsive PSs; these were further characterized by a combination of techniques [1H NMR, dynamic light scattering (DLS), static light scattering (SLS), transmission electron microscopy (TEM), and cryogenic TEM (cryo-TEM)]. The reaction with hydrogen peroxide releases an amphiphilic phenol or a hydrophilic carboxylic acid, which affects polymersome (PS) stability and cargo release. Therefore, the importance of the spacer chemistry in BC deprotection and PS stability and cargo release is herein highlighted. We have also evaluated the impact of spacer chemistry on the PS-specific release of the chemotherapeutic drug doxorubicin (DOX) into tumors in vitro and in vivo. We demonstrate that by spacer chemistry design one can enhance the efficacy of DOX treatments (decrease in tumor growth and prolonged animal survival) in mice bearing EL4 T cell lymphoma. Side effects (weight loss and cardiotoxicity) were also reduced compared to free DOX administration, highlighting the potential of the well-defined ROS-responsive PSs as TME-selective nanomedicines. The PSs could also find applications in other environments with high ROS levels, such as chronic inflammations, aging, diabetes, cardiovascular diseases, and obesity.

High-Molecular-Weight Polyampholytes Synthesized via Daylight-Induced, Initiator-Free Radical Polymerization of Renewable Itaconic Acid.

Herein, it is reported for the first time that when mixed with choline chloride, itaconic acid (IA), normally a low-reactive vinyl monomer, undergoes initiator-free radical polymerization under normal daylight. Furthermore, the process results in the formation of abnormally high-molecular-weight poly(itaconic acid) derivatives with Mw greater than ≈800 000 g mol-1 . Detailed 1D/2D NMR studies indicate that the polymers have two types of ionizable moieties, that is, anionic carboxylic and cationic choline ester groups in an average molar ratio of 12:1. Potentiometric titration shows polyampholyte behavior of the polymers. Tentative mechanistic studies reveal that the daylight-induced polymerization is initiated by species generated via interactions of near UV light with IA. However, EPR findings show that choline also participates in secondary radical reactions. The obtained polyampholytes are useful bio-based materials for fast and straightforward fabrication of polymer-clay nanocomposite hydrogels with excellent mechanical properties.

Rifampicin Nanoformulation Enhances Treatment of Tuberculosis in Zebrafish.

Mycobacterium tuberculosis, the etiologic agent of tuberculosis, is an intracellular pathogen of alveolar macrophages. These cells avidly take up nanoparticles, even without the use of specific targeting ligands, making the use of nanotherapeutics ideal for the treatment of such infections. Methoxy poly(ethylene oxide)- block-poly(ε-caprolactone) nanoparticles of several different polymer blocks' molecular weights and sizes (20-110 nm) were developed and critically compared as carriers for rifampicin, a cornerstone in tuberculosis therapy. The polymeric nanoparticles' uptake, consequent organelle targeting and intracellular degradation were shown to be highly dependent on the nanoparticles' physicochemical properties (the cell uptake half-lives 2.4-21 min, the degradation half-lives 51.6 min-ca. 20 h after the internalization). We show that the nanoparticles are efficiently taken up by macrophages and are able to effectively neutralize the persisting bacilli. Finally, we demonstrate, using a zebrafish model of tuberculosis, that the nanoparticles are well tolerated, have a curative effect, and are significantly more efficient compared to a free form of rifampicin. Hence, these findings demonstrate that this system shows great promise, both in vitro and in vivo, for the treatment of tuberculosis.

N-(2-Hydroxypropyl)methacrylamide-Based Linear, Diblock, and Starlike Polymer Drug Carriers: Advanced Process for Their Simple Production.

We developed a new simplified method for the synthesis of well-defined linear, diblock, or starlike N-(2-hydroxypropyl)methacrylamide (HPMA)-based polymer drug carriers using controlled reversible addition-fragmentation chain transfer polymerization. The prepared monodispersed polymers are after the drug attachment intended for enhanced anticancer therapy. This new approach significantly reduces the number of required synthetic steps and minimizes the consumption of organic solvents during the synthesis. As a result, highly defined linear, diblock, and starlike copolymers designed for pH-triggered drug activation/release in tumor tissue were formed in sufficient amounts for further physicochemical and biological studies. Within the synthesis, we also developed a new procedure for the selective deprotection of tert-butoxycarbonyl hydrazide and amine groups on hydrophilic HPMA copolymers, including the one-pot removal of polymer end groups. We studied and described in detail the kinetics and efficacy of the deprotection reaction. We believe the simplified synthetic approach facilitates the preparation of polymer conjugates bound by the pH-sensitive hydrazone bond and their application in tumor treatment.

Self-Assembled Thermoresponsive Polymeric Nanogels for 19F MR Imaging.

Magnetic resonance imaging using fluorinated contrast agents (19F MRI) enables to achive highcontrast in images due to the negligible fluorine background in living tissues. In this pilot study, we developed new biocompatible, temperature-responsive, and easily synthesized polymeric nanogels containing a sufficient concentration of magnetically equivalent fluorine atoms for 19F MRI purposes. The structure of the nanogels is based on amphiphilic copolymers containing two blocks, a hydrophilic poly[ N-(2-hydroxypropyl)methacrylamide] (PHPMA) or poly(2-methyl-2-oxazoline) (PMeOx) block, and a thermoresponsive poly[ N(2,2difluoroethyl)acrylamide] (PDFEA) block. The thermoresponsive properties of the PDFEA block allow us to control the process of nanogel self-assembly upon its heating in an aqueous solution. Particle size depends on the copolymer composition, and the most promising copolymers with longer thermoresponsive blocks form nanogels of suitable size for angiogenesis imaging or the labeling of cells (approximately 120 nm). The in vitro 19F MRI experiments reveal good sensitivity of the copolymer contrast agents, while the nanogels were proven to be noncytotoxic for several cell lines.

Poly(ethylene oxide monomethyl ether)- block-poly(propylene succinate) Nanoparticles: Synthesis and Characterization, Enzymatic and Cellular Degradation, Micellar Solubilization of Paclitaxel, and in Vitro and in Vivo Evaluation.

Polyester-based nanostructures are widely studied as drug-delivery systems due to their biocompatibility and biodegradability. They are already used in the clinic. In this work, we describe a new and simple biodegradable and biocompatible system as the Food and Drug Administration approved polyesters (poly-ε-caprolactone, polylactic acid, and poly(lactic- co-glycolic acid)) for the delivery of the anticancer drug paclitaxel (PTX) as a model drug. A hydrophobic polyester, poly(propylene succinate) (PPS), was prepared from a nontoxic alcohol (propylene glycol) and monomer from the Krebs's cycle (succinic acid) in two steps via esterification and melt polycondensation. Furthermore, their amphiphilic block copolyester, poly(ethylene oxide monomethyl ether)- block-poly(propylene succinate) (mPEO- b-PPS), was prepared by three steps via esterification followed by melt polycondensation and the addition of mPEO to the PPS macromolecules. Analysis of the in vitro cellular behavior of the prepared nanoparticle carriers (NPs) (enzymatic degradation, uptake, localization, and fluorescence resonance energy-transfer pair degradation studies) was performed by fluorescence studies. PTX was loaded to the NPs of variable sizes (30, 70, and 150 nm), and their in vitro release was evaluated in different cell models and compared with commercial PTX formulations. The mPEO- b-PPS copolymer analysis displays glass transition temperature < body temperature < melting temperature, lower toxicity (including the toxicity of their degradation products), drug solubilization efficacy, stability against spontaneous hydrolysis during transport in bloodstream, and simultaneous enzymatic degradability after uptake into the cells. The detailed cytotoxicity in vitro and in vivo tumor efficacy studies have shown the superior efficacy of the NPs compared with PTX and PTX commercial formulations.

Structure and Dynamics of Alginate Gels Cross-Linked by Polyvalent Ions Probed via Solid State NMR Spectroscopy.

Alginate gels are an outstanding biomaterial widely applicable in tissue engineering, medicine, and pharmacy for cell transplantation, wound healing and efficient bioactive agent delivery, respectively. This contribution provides new and comprehensive insight into the atomic-resolution structure and dynamics of polyvalent ion-cross-linked alginate gels in microbead formulations. By applying various advanced solid-state NMR (ssNMR) spectroscopy techniques, we verified the homogeneous distribution of the cross-linking ions in the alginate gels and the high degree of ion exchange. We also established that the two-component character of the alginate gels arises from the concentration fluctuations of residual water molecules that are preferentially localized along polymer chains containing abundant mannuronic acid (M) residues. These hydrated M-rich blocks tend to self-aggregate into subnanometer domains. The resulting coexistence of two types of alginate chains differing in segmental dynamics was revealed by 1H-13C dipolar profile analysis, which indicated that the average fluctuation angles of the stiff and mobile alginate segments were about 5-9° or 30°, respectively. Next, the 13C CP/MAS NMR spectra indicated that the alginate polymer microstructure was strongly dependent on the type of cross-linking ion. The polymer chain regularity was determined to systematically decrease as the cross-linking ion radius decreased. Consistent with the 1H-1H correlation spectra, regular structures were found for the gels cross-linked by relatively large alkaline earth cations (Ba2+, Sr2+, or Ca2+), whereas the alginate chains cross-linked by bivalent transition metal ions (Zn2+) and trivalent metal cations (Al3+) exhibited significant irregularities. Notably, however, the observed disordering of the alginate chains was exclusively attributed to the M residues, whereas the structurally well-defined gels all contained guluronic acid (G) residues. Therefore, a key role of the units in M-rich blocks as mediators promoting the self-assembly of alginate chains was experimentally confirmed. Finally, combining 2D 27Al 3Q/MAS NMR spectroscopy with density functional theory (DFT) calculations provided previously unreported insight into the structure of the Al3+ cross-linking centers. Notably, even with a low residual amount of water, these cross-linking units adopt exclusively 6-fold octahedral coordination and exhibit significant motion, which considerably reduces quadrupolar coupling constants. Thus, the experimental strategy presented in this study provides a new perspective on cross-linked alginate structure and dynamics for which high-quality diffraction data at the atomic resolution level are inherently unavailable.

Insight into the cryopolymerization to form a poly(N-isopropylacrylamide)/clay macroporous gel: structure and phase evolution.

The cryopolymerization and formation of a macroporous poly(N-isopropylacrylamide) (PNIPA)/clay cryogel were investigated. The mechanism of the cryopolymerization and cryogel formation was elucidated. Two processes, cryostructuration and cryopolymerization, proceed simultaneously and their relative rates determine the structure evolution and the cryogel morphology - porosity. The cryostructuration in the PNIPA/clay system during freezing, controlled by the freezing temperature and the rate of cooling, includes both water and NIPA crystallization, formation of a highly concentrated non-frozen liquid phase (NFLP) and clay aggregation. The rate of cryopolymerization and gelation is governed by the following effects: by a low polymerization temperature and after freezing, by the high cryoconcentration and a steric confinement, manifested by a reduced reagent mobility. Moreover, it depends on the cooling rate and the evolution of cryostructuration. The progress of cryostructuration and cryopolymerization during freezing was described and experimentally proved step by step. Both the phase development during freezing and the progress of cryopolymerization including gelation were monitored in situ by NMR, DSC, chemorheology and SAXS. The morphology and porosity of the cryogels were characterized by SEM and TEM.

System with embedded drug release and nanoparticle degradation sensor showing efficient rifampicin delivery into macrophages.

We have developed a biodegradable, biocompatible system for the delivery of the antituberculotic antibiotic rifampicin with a built-in drug release and nanoparticle degradation fluorescence sensor. Polymer nanoparticles based on poly(ethylene oxide) monomethyl ether-block-poly(ε-caprolactone) were noncovalently loaded with rifampicin, a combination that, to best of our knowledge, was not previously described in the literature, which showed significant benefits. The nanoparticles contain a Förster resonance energy transfer (FRET) system that allows real-time assessment of drug release not only in vitro, but also in living macrophages where the mycobacteria typically reside as hard-to-kill intracellular parasites. The fluorophore also enables in situ monitoring of the enzymatic nanoparticle degradation in the macrophages. We show that the nanoparticles are efficiently taken up by macrophages, where they are very quickly associated with the lysosomal compartment. After drug release, the nanoparticles in the cmacrophages are enzymatically degraded, with half-life 88±11 min.

Thermoresponsive Polymers for Nuclear Medicine: Which Polymer Is the Best?

Thermoresponsive polymers showing cloud point temperatures (CPT) in aqueous solutions are very promising for the construction of various systems in biomedical field. In many of these applications these polymers get in contact with ionizing radiation, e.g., if they are used as carriers for radiopharmaceuticals or during radiation sterilization. Despite this fact, radiosensitivity of these polymers is largely overlooked to date. In this work, we describe the effect of electron beam ionizing radiation on the physicochemical and phase separation properties of selected thermoresponsive polymers with CPT between room and body temperature. Stability of the polymers to radiation (doses 0-20 kGy) in aqueous solutions increased in the order poly(N-vinylcaprolactam) (PVCL, the least stable) ≪ poly[N-(2,2-difluoroethyl)acrylamide] (DFP) < poly(N-isopropylacrylamide) (PNIPAM) ≪ poly(2-isopropyl-2-oxazoline-co-2-n-butyl-2-oxazoline) (POX). Even low doses of ß radiation (1 kGy), which are highly relevant to the storage of polymer radiotherapeutics and sterilization of biomedical systems, cause significant increase in molecular weight due to cross-linking (except for POX, where this effect is weak). In the case of PVCL irradiated with low doses, the increase in molecular weight induced an increase in the CPT of the polymer. For PNIPAM and DFP, there is strong chain hydrophilization leading to an increase in CPT. From this perspective, POX is the most suitable polymer for the construction of delivery systems that experience exposure to radiation, while PVCL is the least suitable and PNIPAM and DFP are suitable only for low radiation demands.

Poly(N-isopropylacrylamide)-clay based hydrogels controlled by the initiating conditions: evolution of structure and gel formation.

The formation of the hydrogel poly(N-isopropylacrylamide)-clay (LAPONITE®) by redox polymerization was investigated, and the main factors governing the gel build-up were determined. The significant effect of the redox initiating system ammonium peroxodisulfate (APS) and tetramethylethylenediamine (TEMED) on gel formation and structure was established, making it possible to control the structure of the gel. Moreover, the pre-reaction stage involving the quality of the clay exfoliation in an aqueous suspension and the interaction of reaction components with the clay play a role in controlling the polymerization and gel structure. The molecular and phase structure evolution during polymerization was followed in situ by the following independent techniques: Fourier transform infrared spectroscopy (FTIR), chemorheology, small-angle X-ray scattering (SAXS) and ultraviolet-visible spectroscopy (UV/Vis). The combination of these methods enabled us to describe in detail particular progress stages during the gel formation and determine the correlation of the corresponding processes on a time and conversion scale. The mechanism of gel formation was refined based on these experimental results.

Tannic acid- and N-acetylcysteine-chitosan-modified magnetic nanoparticles reduce hepatic oxidative stress in prediabetic rats.

Magnetic nanoparticles (MNPs) modified with tannic acid (TA) have shown remarkable success as an antioxidant and antimicrobial therapeutic agent. Herein, we report a synthetic procedure for the preparation of silica-coated MNPs modified with N-acetylcysteine-modified chitosan and TA. This was achieved by free-radical grafting of NAC onto chitosan (CS), a layer-by-layer technique for modifying negatively charged MNP@SiO2 nanoparticles with positively charged CS-NAC, and crosslinking CS with TA. The antioxidant and metabolic effects of MNP@SiO2-CS-NAC and MNP@SiO2-CS-NAC-TA nanoparticles were tested in a model of prediabetic rats with hepatic steatosis, the hereditary hypertriglyceridemic rats (HHTg). The particles exhibited significant antioxidant properties in the liver, increasing the activity of the antioxidant enzymes superoxide dismutase (SOD), glutathione reductase (GR) and glutathione peroxidase (GPx), decreasing the concentration of the lipoperoxidation product malondialdehyde (MDA), and improving the antioxidant status determined as the ratio of reduced to oxidized glutathione; in particular, TA increased some antioxidant parameters. MNPs carrying antioxidants such as NAC and TA could thus represent a promising therapeutic agent for the treatment of various diseases accompanied by increased oxidative stress.

Biodegradable Covalently Crosslinked Poly[N-(2-Hydroxypropyl) Methacrylamide] Nanogels: Preparation and Physicochemical Properties.

Recently, suitably sized polymer-based nanogels containing functional groups for the binding of biologically active substances and ultimately degradable to products that can be removed by glomerular filtration have become extensively studied systems in the field of drug delivery. Herein, we designed and tailored the synthesis of hydrophilic and biodegradable poly[N-(2-hydroxypropyl) methacrylamide-co-N,N'-bis(acryloyl) cystamine-co-6-methacrylamidohexanoyl hydrazine] (PHPMA-BAC-BMH) nanogels. The facile and versatile dispersion polymerization enabled the preparation of nanogels with a diameter below 50 nm, which is the key parameter for efficient and selective passive tumor targeting. The effects of the N,N'-bis(acryloyl) cystamine crosslinker, polymerization composition, and medium including H2O/MetCel and H2O/EtCel on the particle size, particle size distribution, morphology, and polymerization kinetics and copolymer composition were investigated in detail. We demonstrated the formation of a 38 nm colloidally stable PHPMA-BAC-BMH nanogel with a core-shell structure that can be rapidly degraded in the presence of 10 mM glutathione solution under physiologic conditions. The nanogels were stable in an aqueous solution modeling the bloodstream; thus, these nanogels have the potential to become highly important carriers in the drug delivery of various molecules.

Dexamethasone nanomedicines with optimized drug release kinetics tailored for treatment of site-specific rheumatic musculoskeletal diseases.

The application of polymer-based drug delivery systems is advantageous for improved pharmacokinetics, controlled drug release, and decreased side effects of therapeutics for inflammatory disease. Herein, we describe the synthesis and characterization of linear N-(2-hydroxypropyl)methacrylamide-based polymer conjugates designed for controlled release of the anti-inflammatory drug dexamethasone through pH-sensitive bonds. The tailored release rates were achieved by modifying DEX with four oxo-acids introducing reactive oxo groups to the DEX derivatives. Refinement of reaction conditions yielded four well-defined polymer conjugates with varied release profiles which were more pronounced at the lower pH in cell lysosomes. In vitro evaluations in murine peritoneal macrophages, human synovial fibroblasts, and human peripheral blood mononuclear cells demonstrated that neither drug derivatization nor polymer conjugation affected cytotoxicity or anti-inflammatory properties. Subsequent in vivo tests using a murine arthritis model validated the superior anti-inflammatory efficacy of the prepared DEX-bearing conjugates with lower release rates. These nanomedicines showed much higher therapeutic activity compared to the faster release systems or DEX itself.

Physicochemical, structural and biological characterisation of poly(3-hydroxyoctanoate) supplemented with diclofenac acid conjugates - Harnessing the potential in the construction of materials for skin regeneration processes.

This study involved creating oligomeric conjugates of 3-hydroxy fatty acids and diclofenac, named Dic-oligo(3HAs). Advanced NMR techniques confirmed no free diclofenac in the mix. We tested diclofenac release under conditions resembling healthy and chronic wound skin. These oligomers were used to make P(3HO) blends, forming patches for drug delivery. Their preparation used the solvent casting/porogen leaching (SCPL) method. The patches' properties like porosity, roughness, and wettability were thoroughly analysed. Antimicrobial assays showed that Dic-oligo(3HAs) exhibited antimicrobial activity against reference (S. aureus, S. epidermis, S. faecalis) and clinical (Staphylococcus spp.) strains. Human keratinocytes (HaCaT) cell line tests, as per ISO 10993-5, showed no toxicity. A clear link between material roughness and HaCaT cell adhesion was found. Deep cell infiltration was verified using DAPI and phalloidin staining, observed under confocal microscopy. SEM also confirmed HaCaT cell growth on these scaffolds. The strong adhesion and proliferation of HaCaT cells on these materials indicate their potential as wound dressing layers. Additionally, the successful diclofenac release tests point to their applicability in treating both normal and chronic wounds.

Sustainable aerogels based on biobased poly (itaconic acid) for adsorption of cationic dyes.

This work reports the synthesis of poly (itaconic acid) by thermal polymerization mediated by 2,2'-Azobis(2-methylpropionamidine) dihydrochloride. Furthermore, physical hydrogels were prepared by using high molecular weight poly (itaconic acid) characterized by low dispersity and laponite RD. The hydrogels presented porous 3D network structures, with a high-water penetration of almost 2000 g/g of swelling ratio, which can allow the adsorption sites of both poly (itaconic acid) and laponite RD to be easily exposed and facilitate the adsorption of dyes. The water adsorption followed Schott's pseudo-second-order model. The mechanism of the adsorption process was investigated using 1H and 31P NMR. The hydrogel is able to fast adsorb by a combination of electrostatic interactions and hydrogen bonding by the synergic effect of the clay and poly (itaconic acid). Moreover, the prepared aerogels exhibited a fast removal of Basic Fuchsin, with an adsorption capacity of 67.56 mg/g and a high removal efficiency (~99 %). The adsorption followed the pseudo-second-order kinetic model and Langmuir isotherm model. Furthermore, the thermodynamic parameters showed that the BF process of adsorption was spontaneous and feasible, endothermic, and followed physisorption. These results indicated that the PIA/laponite-based aerogel can be considered a promising adsorbent material in textile wastewater treatment.

Poly(glycerol monomethacrylate)-encapsulated upconverting nanoparticles prepared by miniemulsion polymerization: morphology, chemical stability, antifouling properties and toxicity evaluation.

In this report, upconverting NaYF4:Yb3+,Er3+ nanoparticles (UCNPs) were synthesized by high-temperature coprecipitation of lanthanide chlorides and encapsulated in poly(glycerol monomethacrylate) (PGMMA). The UCNP surface was first treated with hydrophobic penta(propylene glycol) methacrylate phosphate (SIPO) to improve colloidal stability and enable encapsulation by reversible addition-fragmentation chain transfer miniemulsion polymerization (RAFT) of glycidyl methacrylate (GMA) in water, followed by its hydrolysis. The resulting UCNP-containing PGMMA particles (UCNP@PGMMA), hundreds of nanometers in diameter, were thoroughly characterized by transmission (TEM) and scanning electron microscopy (SEM), dynamic light scattering (DLS), infrared (FTIR) and fluorescence emission spectroscopy, and thermogravimetric analysis (TGA) in terms of particle morphology, size, polydispersity, luminescence, and composition. The morphology, typically raspberry-like, depended on the GMA/UCNP weight ratio. Coating of the UCNPs with hydrophilic PGMMA provided the UCNPs with antifouling properties while enhancing chemical stability and reducing the cytotoxicity of neat UCNPs to a non-toxic level. In addition, it will allow the binding of molecules such as photosensitizers, thus expanding the possibilities for use in various biomedical applications.