Amphiphilic Block Copolymers

Chitosan is a natural polymer composed of randomly distributed 􀀂-(1-4)-linked D-glucosamine (deacetylated unit) and Nacetyl- D-glucosamine (acetylated unit). It has been described as a non-toxic, biodegradable and biocompatible polymer with very interesting biological properties, such as permeation-enhancing and mucoadhesive properties, anticoagulant and antimicrobial activity and so on. Chitosan has been used in several areas such as biomedical, pharmaceutical and biotechnological fields as well as in the food industry.
Recently, there has been a growing interest in the modification of chitosan to improve its solubility in physiological conditions, to introduce new applications or to improve chitosan biological properties. Research and development on a variety of amphiphilic copolymers containing hydrophobic and hydrophilic segments, have been very active due to their spontaneous self-assembly behaviour in aqueous media These smart transitions often lead to diverse functional compartment structures like micelles, vesicles and gels, which represent promising applications in the field of biotechnology and
pharmaceutics. The aim of the present paper is to review the latest advances in the synthesis of chitosan amphiphilic derivatives with a special emphasis in their applications.

Cyclobutenes containing pendant groups of varying sizes were polymerized via ROMP using Grubbs catalyst 2nd generation (G2). The rate of polymerization depended on the size of the pendant groups attached to the cyclobutene rings, with longer side-chains producing slower polymerization rates and narrower molecular weight distributions.  The polymerization of these new molecules proceeded with first order kinetics, consistent with a living polymerization. Chain extension experiments produced cyclobutene-based diblock copolymers with PDIs below 1.33. The synthetic methods in this report will allow the use of G2 to access new complex polymeric architectures with a higher density of  pendant groups than those derived from norbornene analog and cyclooctene moieties.

In this article, we outline the principles and application of several time-resolved fluorescence techniques for studying the behavior of stimuliresponsive self-assembled polymer systems. We demonstrate the high research potential of fluorescence using results of several published studies performed by the research team at the Charles University in Prague in the framework of the Marie Curie Research Training Network "Self-Organized Nanostructures of Amphiphilic Copolymers" (MRTN-CT-2003-505027). We have chosen several interesting examples of complex self-assembling systems, the behavior of which could not have been understood without the help of targeted fluorescence studies. We have chosen four different techniques, two of them relatively popular (fluorescence anisotropy and nonradiative excitation energy transfer) and two only little used in polymer science (the solvent relaxation method and fluorescence correlation spectroscopy). The last part of the article is devoted to computer simulations (Monte Carlo and molecular dynamics) aimed at the interpretation of fluorescence data.

A facile synthetic route to poly(ethylene imine)-graft-poly(oligo(ethylene glycol methyl ether)) (PEI-graft-POEGMA) functionalised superparamagnetic magnetite nanoparticles is described. The polymerisation of OEGMA from a model molecular amide demonstrated the feasibility of POEGMA synthesis under mild ATRP conditions (20 C in ethanol) albeit with low initiator efficiencies. DFT studies suggest that the amide functionality is intrinsically of lower activity than ester functional monomers and initiators for atom transfer polymerisation (ATRP) as a consequence of higher bond dissociation energies and bond dissociation free energies (BDFE). However these studies further highlighted that use of an appropriate solvent could reduce the free energy of dissociation thereby reducing the relative difference in BDFE between the ester and amide groups. A commercial branched PEI sample was functionalised by reaction with 2-bromo-2-methylpropanoyl bromide giving an amide macroinitiator suitable for the atom transfer radical polymerisation (ATRP) of oligo(ethylene glycol methyl ether) methacrylate. The resulting PEIgraft-POEGMA copolymers were characterised by SEC, FT-IR and 1 H and 13 C NMR spectroscopy. PEI-graft-POEGMA coated magnetite nanoparticles were synthesised by a basic aqueous co-precipitation method and were characterised by transmission electron microscopy, thermogravimetric analysis and vibrating sample magnetometry and dynamic light scattering. These copolymer coated magnetite nanoparticles were demonstrated to be effectively stabilised in an aqueous medium. Overall the particle sizes and magnetic and physical properties of the coated samples were similar to those of uncoated samples. Electronic supplementary information (ESI) available: Plots of Cu(II) function with time; UV-vis absorption spectra of Cu(I)Cl, Cu(II)Cl 2 and Cu(II)Br 2 solutions with DiMePiVA; X-ray diffraction pattern of PEI-gra-POEGMA stabilised nanoparticles; high magnication TEM images of magnetite nanoparticles; pictures of particle suspensions; X-ray diffraction pattern and TEM of bare (unstabilised) nanoparticles 2D 1 H-13 C and 1 H-15 N NMR spectra of PEI; inputs for DFT calculations; Cartesian co-ordinates of energy minimised conformations of initiators. See

The present study reports a promising antioxidant protection by a recently developed micellar propolis formulation, against oxidative stress in in vitro and in vivo models of toxicity. The formulation, based on poplar propolis encapsulated in poly(ethylene oxide)–-poly(propylene oxide)–-poly(ethylene oxide) triblock copolymer (PEO26–PPO40–PEO26) micelles is characterized by small size (Dh = 20 nm), enhances
aqueous solubility and good colloidal stability. In vitro, propolis-loaded PEO26–PPO40–PEO26 micelles (20–100 g/ml) significantly increased the cell viability of human hepatoma HepG2 cells, subjected to H2O2-induced cell injury (0.1 mM, 1 h). Antioxidant activity and protection of the micellar propolis were evaluated in a model of carbon tetrachloride-induced hepatotoxicity in rats (10% CCl4 solution, 1.25 ml/kg,
p.o.) by measurement of non-enzyme (malondialdehyde and glutathione) and enzyme (catalase and superoxide dismutase) biomarkers of oxidative stress. Clinic observations, hematological, biochemical parameters and histological analysis were also performed. In vivo, micellar propolis (20 mg/kg b.w., p.o., 14 days) ameliorated CCl4-induced acute liver injury in rats. The oral administration of micellar propolis significantly prevented serum transaminase increases, as well as brought the levels of malondialdehyde, glutathione, and antioxidant enzymes catalase and superoxide dismutase toward the controls
levels. Therefore, PEO26–PPO40–PEO26 micelles could be considered as a promising oral delivery system
of propolis against oxidative stress injury in liver cells

A series of cyclodextrin-based star polymers were synthesized using -cyclodextrin (CD) as hydrophiliccore, methyl methacrylate (MMA) and tert-butyl acrylate (tBA) as hydrophobic arms. Star polymers, eitherhomopolymers or random/block copolymers, showed narrow molecular weight distributions. Graftinghydrophobic arms created CD-based nanoparticles (CD-NPs) in the size range (130–200 nm) with narrowPdI <0.15 and slightly negative -potential. Particle surface could be modified with chitosan to impart apositive surface charge. Colloidal stability of CD-NPs was a function of pH as revealed by the pH-titrationcurves. CD-NPs were used as carrier for the chemotherapeutic drug idarubicin (encapsulation efficiency,EE ∼40%) ensuring prolonged release profile (∼80% after 48 h). For cell-based studies, coumarin-6 wasencapsulated as a fluorescent marker (EE ∼75%). Uptake studies carried out on A549 and Caco-2 celllines proved the uptake of coumarin-loaded NPs as a function of time and preferential localization in thecytoplasm. Uptake kinetics revealed no saturation or plateau over 6 h. Chitosan-modified NPs showed sig-nificantly improved, concentration-dependent cellular uptake. Meanwhile, CD-NPs were non-cytotoxicon both cell lines over the concentration range (0.25–3 mg/ml) as studied by MTT and LDH assays. Inconclusion, CD star polymers can be considered a versatile platform for a new class of biocompatiblenanochemotherapy.

A facile synthetic route to poly(ethylene imine)-graft-poly(oligo(ethylene glycol methyl ether)) (PEI-graft-POEGMA) functionalised superparamagnetic magnetite nanoparticles is described. The polymerisation of OEGMA from a model molecular amide demonstrated the feasibility of POEGMA synthesis under mild ATRP conditions (20 °C in ethanol) albeit with low initiator efficiencies. DFT studies suggest that the amide functionality is intrinsically of lower activity than ester functional monomers and initiators for atom transfer polymerisation (ATRP) as a consequence of higher bond dissociation energies and bond dissociation free energies (BDFE). However these studies further highlighted that use of an appropriate solvent could reduce the free energy of dissociation thereby reducing the relative difference in BDFE between the ester and amide groups. A commercial branched PEI sample was functionalised by reaction with 2-bromo-2-methylpropanoyl bromide giving an amide macroinitiator suitable for the atom transfer radical polymerisation (ATRP) of oligo(ethylene glycol methyl ether) methacrylate. The resulting PEI-graft-POEGMA copolymers were characterised by SEC, FT-IR and 1H and 13C NMR spectroscopy. PEI-graft-POEGMA coated magnetite nanoparticles were synthesised by a basic aqueous co-precipitation method and were characterised by transmission electron microscopy, thermogravimetric analysis and vibrating sample magnetometry and dynamic light scattering. These copolymer coated magnetite nanoparticles were demonstrated to be effectively stabilised in an aqueous medium. Overall the particle sizes and magnetic and physical properties of the coated samples were similar to those of uncoated samples.

Self‐standing isoporous membranes based on amphiphilic block copolymers (BCPs) are an outstanding candidate for efficient separation processes. Such fascinating membranes have been generated through combining the BCP self‐assembly (micro‐phase separation) together with the classical non‐solvent induced phase separation (macro‐phase separation), known as SNIPS process. However, the controllability, reproducibility and cost‐effectiveness of the process along with the mechanism for pores generation are still challenging in the SNIPS strategy, especially when a new BCP or conditions utilized. It is mainly due to the narrow efficacy window of numerous variables influencing on the desired structure formation. In this review, first an overview of the one‐step readily scalable SNIPS technique and the stepwise explanation of the process is given. Then the formation mechanism of SNIPS membranes, according to the related hypotheses and assumptions proposed on the basis of experimental evidence so far, is presented and discussed. As the main focus of this paper, governing factors in the SNIPS process in which affect the preparation and structural characteristics of final membrane structures are entirely reviewed and interpreted. This review will help to have a better understanding of the connection between determinant factors and final membrane structure, which facilitate successful preparation of BCP membranes via SNIPS. This article is protected by copyright. All rights reserved

There is a growing demand on the studies of the wound healing potentials of photodynamic therapy. Here we analyze the effects of Fotoditazin, an e6 chlorine derivative, and its complexes with amphiphilic polymers, on the early stage of wound healing in a rat model. A skin excision wound model with prevented contraction was developed in male albino rats divided into eight groups according to the treatment mode. All animals received injections of one of the studied compositions into their wound beds and underwent low-intensity laser irradiation or stayed un-irradiated. The clinical monitoring and histological examination of the wounds were performed. It has been found that all the Fotoditazin formulations have significant effects on the early stage of wound healing. The superposition of the inflammation and regeneration was the main difference between groups. The aqueous solution of Fotoditazin alone induced a significant capillary hemorrhage, while its combinations with amphiphilic polymers did not. The best clinical and morphological results were obtained for the Fotoditazin-Pluronic F127 composition. Compositions of Fotoditazin and amphiphilic polymers, especially Pluronic F127, probably, have a great potential for therapy of wounds. Their effects can be attributed to the increased regeneration and suppressed reactions changes at the early stages of repair.

Strongly segregated diblock copolymer of polystyrene-block-poly (acrylic acid) (PS-b-PAA) was used to fabricate asymmetric isoporous membranes through self-assembly and nonsolvent induced phase separation (SNIPS) process. However, thus far, PS-b-PAA isoporous membrane could not be fabricated directly through the SNIPS method without the aid of a foreign additive. Accordingly, herein additive-free isoporous PS-b-PAA membranes were directly prepared through SNIPS process in the simplest possible way. The casting solution prepared by only a single solvent and relatively low polymer concentrations were used to produced the membranes. The highly ordered surface pores with monodispersed diameters in the sub-10 nm range and lengths in the 150 nm range were formed with high pore density (pore density > 3 × 1014 pores per m2) based on a macro-porous sublayer, resulting in a high performance for the membranes.

Micellization and micellar gel formation of poly(styrene)block-poly(methyl methacrylate) [PS-b-PMMA] are demonstrated in a water-ethanol solvent mixture; full hydration of the PMMA causes a large radius of gyration resulting in micellar gel formation at only 1 wt% polymer concentration.

The objective of the present study is the introduction of well known and readily accessible analytical methods as FTIR, thermogravimetric (TGA) and evolved gas analysis (EGA) for quantitative determination of the degree of polymerization (DP) and degree of quaternization (DQ)/betainization (DB) of amino-based amphiphilic block copolymers. For this purpose a series of amphiphilic poly(dimethylsiloxane)-b-poly[2-{dimethylamino)ethyl methacrylate] (PDMS-b-DMAEMA) diblock copolymers with DP of the PDMAEMA-block ranging from 22 to 162 was synthesized by atom transfer radical polymerization and analyzed by 1 H NMR, ATR-FTIR and TGA-co-EGA. The determined composition results have shown linear correlation between the FTIR or TGA and the 1 H NMR data and equations allowing the quantitative calculation of PDMAEMA-block DP were found. The errors estimated by ATR-FTIR were less than 1.5%. Further, the PDMAEMA-block was quaternized (or betainized) with DQ (or DB) from 25 % to 100 % and analyzed by TGA-co-EGA. Again, a linear correlation between the quaternized (betainized) PDMAEMA-block mass fraction and the DQ (DB) degrees was obtained by 1 H NMR.

The objective of the present study is the introduction of well known and readily accessible analytical methods as FTIR, thermogravimetric (TGA) and evolved gas analysis (EGA) for quantitative determination of the degree of polymerization (DP) and degree of quaternization (DQ)/betainization (DB) of amino-based amphiphilic block copolymers. For this purpose a series of amphiphilic poly(dimethylsiloxane)-b-poly[2-{dimethylamino)ethyl methacrylate] (PDMS-b-DMAEMA) diblock copolymers with DP of the PDMAEMA-block ranging from 22 to 162 was synthesized by atom transfer radical polymerization and analyzed by 1 H NMR, ATR-FTIR and TGA-co-EGA. The determined composition results have shown linear correlation between the FTIR or TGA and the 1 H NMR data and equations allowing the quantitative calculation of PDMAEMA-block DP were found. The errors estimated by ATR-FTIR were less than 1.5%. Further, the PDMAEMA-block was quaternized (or betainized) with DQ (or DB) from 25 % to 100 % and analyzed by TGA-co-EGA. Again, a linear correlation between the quaternized (betainized) PDMAEMA-block mass fraction and the DQ (DB) degrees was obtained by 1 H NMR.