Biodegradable poly(l-lactic acid)-poly(ethylene glycol)-poly(l-lactic acid) (PLLA-PEG-PLLA) copolymers were synthesized by ring-opening polymerization of l-lactide using dihydroxy PEG as the initiator. The effects of different PEG segments in the copolymers on the mechanical and permeative properties were investigated. It was determined that certain additions of PEG result in composition-dependent microphase separation structures with both PLLA and PEG blocks in the amorphous state. Amorphous PEGs with high CO2 affinity form gas passages that provide excellent CO2/O2 permselectivity in such a nanostructure morphology. The gas permeability and permselectivity depend on the molecular weight and content of the PEG and are influenced by the temperature. Copolymers that have a higher molecular weight and content of PEG present better CO2 permeability at higher temperatures but provide better CO2/O2 permselectivity at lower temperatures. In addition, the hydrophilic PEG segments improve the water vapor permeability of PLLA. Such biodegradable copolymers have great potential for use as fresh product packaging.

Photocurable hydrogel scaffolds for tissue engineering must have excellent biocompatibility, tunable mechanical characteristics, and be biodegradable at a controllable rate. Hydrogels developed as ink for 3D printing require several other properties such as optimal viscosity and shorter photocrosslinking time to ensure continuous extrusion and to avoid untimely collapse of the printed structure. Here, a novel photocurable hydrogel made of acrylated poly(ethylene glycol)-co-poly(xylitol sebacate) (PEXS-A) is developed for tissue engineering and 3D printing applications. Synthesis of PEXS-A hydrogel with equilibrated water content above 90% is achieved via a quick and facile photopolymerization process. Changing the acrylation ratio of the PEXS-A hydrogel has an impact on its crosslinking density, mechanical properties and degradation rate, thus highlighting PEXS-A tunability. PEXS-A could be employed as ink as demonstrated by the 3D printing of a 30-layers cubic grid with high structural integrity. Furthermore, 3T3 fibroblast cells encapsulated into PEXS-A during photocrosslinking maintain a viability of 93.76% after seven days, which showed the good biocompatibility of this novel hydrogel. These results indicate that PEXS-A hydrogel could have multiple applications including as 3D printing ink and as tissue engineering scaffold.

The thermoresponsive ionic liquid diblock copolymer of poly[1-(4-vinylbenzyl)-3-methylimidazolium tetrafluoroborate]-block-poly(N-isopropylacrylamide) (P[VBMI][BF4]-b-PNIPAM) containing a hydrophilic poly(ionic liquid) block of P[VBMI][BF4] is prepared by sequential reversible addition-fragmentation chain transfer (RAFT) polymerization. This P[VBMI][BF4]-b-PNIPAM exhibits an abnormal thermoresponsive phase transition at a temperature above the phase transition temperature (PTT) of the PNIPAM block. For P[VBMI][BF4]-b-PNIPAM including a short P[VBMI][BF4] block, its aqueous solution becomes turbid at a temperature above the PTT of the thermoresponsive PNIPAM block, whereas for P[VBMI][BF4]-b-PNIPAM containing a relatively long P[VBMI][BF4] block even in the case of a relatively long PNIPAM block, the aqueous solution remains transparent at a temperature far above the PTT of the PNIPAM block, although a soluble-to-insoluble phase transition of the PINIPAM block is confirmed by dynamic light scattering (DLS) analysis and variable temperature 1H NMR analysis. The reason that P[VBMI][BF4]-b-PNIPAM exhibits an abnormal thermoresponse is discussed and ascribed to the highly hydrophilic and charged poly(ionic liquid) block of P[VBMI][BF4] leading to the formation of small-sized micelles at a temperature above the PTT.

In the present study, camptothecin grafted poly amino ester-methyl ether polyethylene glycol (CPT-PEA-MPEG) as a novel copolymer was synthesized by Michael reaction at different ratios of MPEG and CPT (60 : 40 and 80 : 20). The microemulsion was used to prepare nanomicelles, and in vitro cytotoxicity was performed on the HT29 cell line, and cell survival was measured by MTT assay. The syntheses were confirmed by 1H NMR and FT-IR. Several characterization methods including CMC, particle size, size distribution, and transmission electron microscopy were performed to evaluate features of prepared nanomicelles. Low critical micelle concentration, small particle size and IC50 of 0.1 mg ml-1 at MPEG to CPT ratio of 60 : 40 make this micelle a promising drug delivery carrier. CPT-PAE-MPEG nanomicelles at a MPEG : CPT ratio of 60 : 40 can be a suitable choice to improve the physiochemical properties of CPT and its therapeutic effect, while it can be potentially used as a nano-carrier for other anticancer drugs to purpose a dual drug delivery.

Sustained release dosage forms enable prolonged and continuous release of a drug in the gastrointestinal tract for medication characterized by a short half lifetime. In this study, the effect of blending polyamine on poly(3-hydroxybutyrate) (PHB) as a carrier for norfloxacin (NF) was studied. The prepared blend was mixed with different amounts of NiO nanoparticles and characterized using FTIR analysis, X-ray diffraction analysis, thermogravimetric analysis, dynamic light scattering, transmission electron microscopy and scanning electron microscopy. It was found that the drug released from the nanocomposite has a slow rate in comparison with NiO, PHB, and PHB/polyamine blend. The highest ratio of NiO content to the matrix (highest NF loading), leads to a slower rate of drug release. The release from the nanocomposites showed a faster rate at pH = 2 than that at pH = 7.4. The mechanisms of NF adsorption and release were studied on PHB/polyamine-3% NiO nanocomposite. In addition, the antimicrobial efficacy of nanocomposites loaded with the drug was determined and compared with the free drug. Inclusion of NiO into PHB/polyamine showed a higher efficacy against Streptococcus pyogenes and Pseudomonas aeruginosa than the free NF. Moreover, the cytotoxicity of PHB/polyamine-3% NiO against HePG-2 cells was investigated and compared with PHB and PHB/polyamine loaded with the drug. The most efficient IC50 was found for NF@PHB/polyamine-3% NiO (29.67 μg mL-1). No effect on cell proliferation against the normal human cell line (WISH) was observed and IC50 was detected to be 44.95 and 70 μg mL-1 for NiO nanoparticles and the PHB/polyamine-3% NiO nanocomposite, respectively indicating a selectivity of action towards tumor cells coupled with a lack of cytotoxicity towards normal cells.

The present work deals with the synthesis and characterization of a novel nucleoamino acid derivative based on a l-tyrosine moiety to which a thymine nucleobase was anchored by means of an amide bond to the N-alpha group. This derivative, denominated by us TyrT, belongs to the family of the nucleobase-amino acid conjugates that show a wide range of biological activities, frequently associated with their ability to interact with nucleic acids. In this respect, the interaction of TyrT with poly(A), a proposed RNA target for anticancer strategies, was studied by circular dichroism (CD) which suggested its ability to bind this RNA. Moreover, the modification of the morphology of a sample of TyrT in the presence of poly(A) was visualised by scanning electron microscopy (SEM) which was in agreement with the evidence that the thyminyl l-tyrosine interacts with poly(A). Finally, computational analyses have been performed to hypothesize the binding mode from a structural point of view, suggesting that the binding is mainly kept via hydrophobic contacts, reproducing a stacking-like interaction between the thymine ring of TyrT and the two successive adenine rings of a poly(A) model.

Aqueous self-assembly of amphiphilic block copolymers is studied extensively for biomedical applications like drug delivery and nanoreactors. The commonly used hydrophilic block poly(ethylene oxide) (PEO), however, suffers from several drawbacks. As a potent alternative, poly(glycidol) (PG) has gained increasing interest, benefiting from its easy synthesis, high biocompatibility and flexibility as well as enhanced functionality compared to PEO. In this study, we present a quick and well-controlled synthesis of poly(butylene oxide)-block-poly(glycidol) (PBO-b-PG) amphiphilic diblock copolymers together with a straight-forward self-assembly protocol. Depending on the hydrophilic mass fraction of the copolymer, nanoscopic micelles, worms and polymersomes were formed as well as microscopic giant unilamellar vesicles. The particles were analysed regarding their size and shape, using dynamic and static light scattering, TEM and Cryo-TEM imaging as well as confocal laser scanning microscopy. We have discovered a strong dependence of the formed morphology on the self-assembly method and show that only solvent exchange leads to the formation of homogenous phases. Thus, a variety of different structures can be obtained from a highly flexible copolymer, justifying a potential use in biomedical applications.

Self-assembly of block copolymers is a significant area of polymer science. The self-assembly of completely water-soluble block copolymers is of particular interest, albeit a challenging task. In the present work the self-assembly of a linear-brush architecture block copolymer, namely poly(N-vinylpyrrolidone)-b-poly(oligoethylene glycol methacrylate) (PVP-b-POEGMA), in water is studied. Moreover, the assembled structures are crosslinked via α-CD host/guest complexation in a supramolecular way. The crosslinking shifts the equilibrium toward aggregate formation without switching off the dynamic equilibrium of double hydrophilic block copolymer (DHBC). As a consequence, the self-assembly efficiency is improved without extinguishing the unique DHBC self-assembly behavior. In addition, decrosslinking could be induced without a change in concentration by adding a competing complexation agent for α-CD. The self-assembly behavior was followed by DLS measurement, while the presence of the particles could be observed via cryo-TEM before and after crosslinking.

Composite films containing poly(vinyl alcohol) filled with different amounts of graphene oxide (2 and 4 wt%) were prepared by the solution casting technique, and the mechanical properties of the resulting materials were modified with different amounts of glycerol as a plasticizer. Two series of pure poly(vinyl alcohol) and graphene oxide-loaded films with fixed amounts of water were used for modification with glycerol, since water can also serve as a plasticizer for poly(vinyl alcohol). The morphology and physical properties of the plasticized and non-plasticized composites were studied; tensile tests were performed to investigate and compare their mechanical properties. Glycerol addition does not affect the excellent compatibility of the filler with the polymer matrix and uniform distribution of graphene oxide in poly(vinyl alcohol). For poly(vinyl alcohol)/graphene oxide films an increase of the Young's modulus and yield stress was found with an increase of the filler content; the Young's modulus for poly(vinyl alcohol) filled with 4 wt% of graphene oxide is almost two times higher than that of the pure polymer. Simultaneously, a sharp decrease of the elongation at break from 80% for pure PVA to about 5% for the PVA/GO composite with 4 wt% of GO is observed, and the film's brittleness dramatically increases. It was shown that the addition of glycerol to the composite films leads both to the Young's modulus decrease and tensile energy at break increase; here the Young's modulus decreases by 18 times after addition of 20 wt% of glycerol to the poly(vinyl alcohol) film filled with 4 wt% of graphene oxide. Thus, the use of plasticizer results in a significant increase of the ductile properties of graphene oxide filled poly(vinyl alcohol) composite films, and the higher the water content in the composite film, the more drastic the increase of the ductile properties observed.

A two-photon absorbing (2PA) red emitter group was chemically conjugated onto amphiphilic poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-b-PCL) copolymers, and further grafted with cyclo (Arg-Gly-Asp) (cRGD) peptide to form micelle 1. Micelle 1 with cRGD targeting groups were used for targeted bioimaging. For comparison, micelle 2 without the cRGD targeting groups were also prepared and investigated. The micelles were characterized using dynamic light scattering (DLS), showing average diameters of around 77 nm. The cRGD targeting group is known to bind specifically with α v β 3 integrin in cancer cells. In this study, α v β 3 integrin overexpressed human glioblastoma U87MG cell line and α v β 3 integrin deficient human cervical cancer HeLa cell line were chosen. Results showed that the cRGD targeting group enhanced the cellular uptake efficiency of the micelles significantly in α v β 3 integrin rich U87MG cells. Higher temperature (37 °C versus 4 °C) and calcium ions (with 3M calcium chloride in the cell culture medium versus no addition of calcium ions) enhanced the cellular uptake efficiency, suggesting that the uptake of the micelles is through the endocytosis pathway in cells. A 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) viability assay was used to evaluate the cytotoxicity of the micelles and no significant cytotoxicity was observed. The BTD-containing two-photon absorbing emitter in the micelles showed a two-photon absorbing cross-section of 236 GM (1GM = 1 × 10-50 cm4 s photon-1 molecule-1) at 820 nm, which is among the highest values reported for red 2PA emitters. Because of the two-photon absorbing characteristics, micelle 1 was successfully used for two-photon fluorescence imaging targeted to U87MG cells under a two-photon fluorescence microscope. This study is the first report regarding the targeted imaging of a specific cancer cell line (herein, U87MG) using the BTD-conjugated-fluorophore-containing block copolymers.

Poly(propylene imine) dendromesogens (generations from 1 to 4) have been utilized for the synthesis and stabilization of ferrimagnetic Fe2O3 nanoparticles. Reduction of Fe(iii) with further oxidation of Fe(ii) results in the formation of highly soluble nanocomposites of iron oxides in a dendrimer, which are stable under a wide range of temperatures. The magnetic iron oxide nanoparticles were investigated by MALDI-ToF MS spectrometry and elemental analysis. To establish the type of mesophase, X-ray measurements were performed at different temperatures. The calculations of X-ray results demonstrate a hexagonal columnar packing of the molecules in the mesophase. Observation of the samples by TEM gives information about the size of the compounds as well as direct evidence of the implementation of Fe2O3 nanoparticles into dendrimers. Physical parameters of the magnetic nanoparticles (magnetic moment, effective magnetic anisotropy) have been determined from analyses of the EPR data.

A novel antibacterial agent was synthesized using 2-(dimethylamino)ethyl methacrylate (DM) and sodium 3-chloro-2-hydroxypropane sulfonate (CHPS). It was characterized by Fourier transform infrared spectroscopy (FTIR), NMR Spectroscopy (1H NMR), and X-ray photoelectron spectroscopy (XPS). This new agent DMCHPS was then grafted onto a polyurethane (PU) substrate via surface-initiated reverse atom transfer radical polymerization (SI-RATRP). The modified PU was characterized by FTIR and XPS. The hydrophilic properties of the PU surface before and after the incorporation of DMCHPS were determined by static contact angle (SCA) measurements. The results showed that the hydrophilicity of the PU surface after the modification was remarkably improved. MIC tests and bacterial adhesion confirmed that modified PU has good antibacterial properties. Protein adsorption experiments show that the material has a certain ability to resist pollution. Furthermore, the high survival rate of HEK293 human embryonic kidney cells shows that the modified PU has a potential use as a medicinal material.

A novel bio-based thermoplastic vulcanizate (TPV) material consisting of poly(lactic acid) (PLA) and a novel polymeric slide ring material (SeRM) was fabricated via isocyanate-induced dynamic vulcanization. The microscopic morphology, thermal properties, biocompatibility, and mechanical properties of the SeRM/PLA TPV material were comprehensively investigated, in turn by transmission electron microscopy, differential scanning calorimetry, in vitro cytotoxicity test, electron tension machine, and molecular dynamics simulations. Phase inversion in TPV was observed during the dynamic vulcanization, and TEM images showed that SeRM particles that were dispersed in PLA continuous phase had an average diameter of 1-4 μm. Results also indicated that an optimum phase inversion morphology was obtained at the SeRM/PLA blending ratio of 70/30 w/w. Glass transition temperature of PLA was found to be slightly decreased, owing to the improvement in interface compatibility by chemically bonding the PCL side chains (of SeRM molecules) and PLA chains. The tensile strength and elongation at break of TPVs were approximately 14.7 MPa and 164%, respectively, at SeRM/PLA blending ratio of 70/30, owing to the unique sliding effect of SeRM molecules when subjected to deformations. Cytotoxicity test results proved that the bio-based TPVs were fully non-toxic to L929 cells. In such aspects we believe that the bio-based TPV can be a promising material in the biomedical applications as an alternative of traditional commodity plastics.

Poly(allylamine hydrochloride)-methotrexate (PAH-MTX) nanoassemblies with novel morphologies (i.e. nanostrips, nanorolls, nanosheets, and nanospheres) were achieved for the first time via supramolecular self-assembly directed by the synergistic action of various non-covalent interactions between PAH and MTX molecules in aqueous solution. Herein, MTX acted in a versatile manner as both a morphology-regulating agent and a small molecular hydrophobic anticancer drug. Moreover, different morphologies presented diverse drug release profiles, which may be caused by the distinctive interactions between PAH and MTX molecules. Synergistically non-covalent interactions, including electrostatic interactions, van der Waals forces, and hydrogen bonding, favored easier matrix corrosion and more rapid drug release of non-spherical structures (i.e. nanostrips, nanorolls, and nanosheets) through the ligand exchange process. On the other hand, the highly sealed encapsulation mode for hydrophobic MTX molecules made the nanospheres exhibit slower and better controlled release. In addition, in vitro bioassay tests showed that nanostrips displayed the most obvious suppression on the viability of cancer cells among other morphologies, especially after a longer duration. The strategy of using small molecular anticancer drugs not as passively delivered cargoes but as effective molecular building blocks, opens up a new way to develop self-delivering drugs for anticancer therapy.

This work describes the suitability of a polyethylene styrene-DVB based interpolymer cation exchange membrane for use in a highly alkaline redox flow battery (RFB) with a [Fe(TEA)OH]2-/[Fe(TEA)OH]- and Fe(CN)6 3-/Fe(CN)6 4- redox couple. The alkaline stability of the membrane for 1440 h was evaluated in 5 N NaOH containing a 200 mM Fe(CN)6 3-/Fe(CN)6 4- redox couple. It was assessed according to the changes in the electrochemical and physicochemical properties. The performance of the membrane was evaluated over 40 charge-discharge cycles at a current density of 5 mA cm-2 current in a designed RFB cell. The obtained average coulombic efficiency (CE) was 92%, energy efficiency (EE) was 75%, voltage efficiency (VE) was 82% and volumetric efficiency was 34%. Under identical experimental conditions, the values of CE, EE, and VE for Nafion®-112 were 99%, 75%, and 76%, respectively. These results indicate the suitability of the polyethylene styrene-DVB based interpolymer cation exchange membrane for use in an alkaline RFB.

The environmentally friendly polymerization process was carried out using microwave irradiation without additional solvents or catalysts to produce poly(β-amino ester) (PβAE) which served as a drug delivery system. PβAE was synthesized through Michael addition polymerization of 1,4-butane diol diacrylate and piperazine. Swelling and biodegradation studies were conducted in various solvents and phosphate-buffered saline (PBS, pH 7.4) at 37 °C to evaluate the properties of the polymeric gel. The PβAE matrix demonstrated solubility enhancement for hydrophobic antimicrobial and antitumor-active nicotinamide derivatives (TEINH, APTAT, and MOAPM), controlling their release over 10 days in (PBS). The successful formation of free and loaded PβAE with nicotinamide active materials was confirmed by spectroscopic analysis including Fourier-transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). Optimization and physical descriptor determination via the DFT/B3LYP-631(G) basis set were performed to aid in the biological evaluation of these compounds with elucidation of their physical and chemical interaction between poly(β-amino ester) and nicotinamide drugs.

In this study, in order to obtain hydrogels with good properties for sustained release of hydrophobic drugs or for tissue engineering, poly(vinyl alcohol) (PVA)/silk fibroin (SF) semi-interpenetrating (semi-IPN) hydrogels with varied ratios of PVA/SF were enzymatically cross-linked using horseradish peroxidase. A vial inversion test determined approximate gelation times of PVA/SF hydrogels ranging from 5 to 10 min. The hydrogels with varied ratios showed differences in pore size and morphology. Mass loss rate of hydrogels increased from 15% to 58% with increasing PVA concentration. Stable hydrogels with PVA/SF at 0.5 : 1 w/w showed the best swelling ratio values in distilled water (7.36). FTIR analysis revealed that silk fibroin in these hydrogels exhibited the coexistence of amorphous and silk I crystalline structures and the SF and PVA molecules interacted with each other well. The mechanical properties of the composite hydrogels were controlled by the SF content. From the cell viability results, it was found that the hydrogels exerted very low cytotoxicity. Paeonol was chosen as the hydrophobic drug model for release studies from the hydrogels. Paeonol can be uniformly loaded into the composite hydrogels using the emulsifying property of PVA and paeonol release from the hydrogels was dependent on the PVA/SF ratio. This study applied a novel type of enzymatically crosslinked semi-IPN hydrogel that may have potential applications in drug delivery.

Electrospun polymer/inorganic biomimetic nanocomposite scaffolds have emerged for use in a new strategy for bone regeneration. In this study, a poly(ε-caprolactone) (PCL)/hydroxyapatite (HAp) nanocomposite mat with a HAp content as high as 60% was prepared via one-step electrospinning using trifluoroethanol as the solvent, and it has superior dispersibility and spinnability. The structure and physicochemical properties of the scaffolds were studied using scanning electron microscopy and spectroscopic techniques. X-ray diffraction and Fourier transformed infrared spectroscopy confirmed the presence of HAp in the composite PCL fibers. The results of cell culturing suggested that the incorporation of HAp with PCL could regulate the cytoskeleton and the differentiation of cells. More interestingly, the high content of HAp was also found to be conducive to the infiltration of MC-3T3 cells into the mat. The results indicated the potential of PCL/HAp scaffolds as a promising substitute for bone regeneration.

Folic acid tagged and hydrophilic polymer containing solid lipid nanoparticles (SLNs) were formulated for the controlled and targeted delivery of gemcitabine, a hydrophilic drug. Drug loaded SLNs were prepared by double emulsion method and optimized by 32 level factorial design. Then, a hydrophilic polymer, namely, poly(N-vinylcaprolactam) (PVCL) was incorporated in the optimized SLN batch in the first aqueous phase (W1) to obtain solid lipid polymer hybrid nanoparticles (SLPHNs) that were further decorated with folic acid (F-SLPHNs). TEM analysis of SLNs and SLPHNs revealed the spherical shape with no aggregation while SLPHNs showed higher % EE. SLPHNs exhibited limited burst release of gemcitabine compared to SLNs as well as lower overall % release. All the formulations showed good cytocompatibility against MDA-MB-231 cell lines and folic acid-tagged hybrid particles (F-SLPHNs) showed remarkably higher cellular uptake.

Thermo-responsive hyperbranched copoly(bis(N,N-ethyl acrylamide)/(N,N-methylene bisacrylamide)) (HPEAM-MBA) was synthesized by using reversible addition-fragmentation chain-transfer polymerization (RAFT). Interestingly, the zinc ion (Zn2+) was found to have a crucial influence on the lowest critical solution temperature (LCST) of the thermo-responsive polymer. The tetraphenylethylene (TPE) unit was then introduced onto the backbone of the as-prepared thermo-responsive polymer, which endows a Zn2+-responsive "turn-off" effect on the fluorescence properties. The TPE-bearing polymer shows a highly specific response over other metal ions and the "turn-off" response can even be tracked as the concentration of Zn2+ reduces to 2 × 10-5 M. The decrement of fluorescence intensity was linearly dependent on the concentration of Zn2+ in the range of 4-18 μmol L-1. The flexible, versatile and feasible approach, as well as the excellent detection performance, may generate a new type of Zn2+ probe without the tedious synthesis of the moiety bearing Zn2+ recognition units.