Amphiphilic polylactide-poly(ethylene oxide)-poly(propylene oxide) block copolymers: Self-assembly behavior and cell affinity

Polylactide (PLA) is a biodegradable polyester recognized for its potential use as a biomedical material. Poly(ethylene oxide) (PEO) and copolymers based on PEO and poly(propylene oxide) (PPO) are biocompatible polyethers widely applied in the biomedical field, particularly as macromolecular nonionic surfactants. In this work, PLA blocks were attached to the PEO and to the PEO and PPO-based triblock copolymer PEO–PPO–PEO, through ring-opening polymerization of racemic lactide (rac-LA) to obtain the amphiphilic triblock PLA–PEO–PLA and pentablock PLA–PEO–PPO–PEO–PLA copolymers containing hydrophilic/hydrophobic blocks with variable block mass ratios. The copolymers were evaluated for chemical composition, molar mass, and thermal properties, and they were used to prepare self-assemble aggregates in water from tetrahydrofuran polymer solutions. The combination of scattering light experiments and microscopy techniques revealed the spherical morphology of the aggregates with diameters around 180–200 nm, which comprises a hydrophobic PLA core and a hydrophilic polyether shell. The aggregates are nontoxic to human cervical cancer cell line — HeLa cells, as determined by MTS assay, and the aggregates are potential candidates to be applied in the encapsulation of hydrophobic compounds. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018 , 56, 2203–2213     

Block copolymer-directed metal nanoparticle morphogenesis and organization

Advances in the nanoscale design of polymeric, “soft” materials and of metallic, “hard” materials can converge at the “interfaces” to form hybrid nanomaterials with interesting features. Novel optical, magnetic, electronic, and catalytic properties are conferred by metal nanoparticles, depending on their morphology (size and shape), surface properties, and long-range organization. We review here the utilization of block copolymers for the controlled synthesis and stabilization of metal nanoparticles. Solvated block copolymers can provide nanoscale environments of varying and tunable shape, dimensions, mobility, local polarity, concentration, and reactivity. In particular, block copolymers containing poly(ethylene oxide) can exhibit multiple functions on the basis of their organization at the intra-polymer level (i.e., crown ether-like cavities that bind and reduce metal ions), and at the supramolecular level (surface-adsorbed micelles, and ordered arrays of micelles). These block copolymers can thus initiate metal nanoparticle formation, and control the nanoparticle size and shape. The physically adsorbed block copolymers, which can be subsequently removed or exchanged with other functional ligands, stabilize the nanoparticles and can facilitate their integration into diverse processes and products. Block copolymers can be further useful in promoting long-range nanoparticle organization. Several studies have elucidated the nanoparticle synthesis and stabilization mechanism, optimized the conditions for different outcomes, extended the ranges of materials obtained and applications impacted, and generalized the scope of this functional polymer-based nanoparticle synthesis methodology.     

Micellization-induced deprotonation of thermoresponsive surfactant CAE-85 — the telechelic carboxylic group derivative of Pluronic P85

Temperature-induced micellization of CAE-85, a carboxylic acid end-standing derivative of a triblock copolymer Pluronic P85, was studied by attenuated total reflectance Fourier-transform infrared spectroscopy (ATR FTIR) and density functional theory (DFT) model calculations. It was found that in polymer micelles carboxyl end groups dissociated and it was a two stage process. The first stage of deprotonation appeared with the onset of micellization and it was in agreement with predictions of existing models and theories for ionization processes in micellar corona. In micelles well above the critical micellization temperature, the degree of CAE-85 deprotonation increased further to values significantly higher compared to unimer solution. It is proposed that such deprotonation correlates with the formation of hydrogen bonded carboxyl end groups enabled by sufficient density of chains in the corona of developing micelles. It was demonstrated that the proton dissociation constant, pK_m, specific to the micellar form existed and was different from the proton dissociation constant of solution of unimers, pK_a.     

Synthesis and characterization of novel amphiphilic copolymer stearic acid-coupled F127 nanoparticles for nano-technology based drug delivery system

Pluronic, F127, amphiphilic block copolymers, are used for several applications, including drug delivery systems. The critical micelle concentration (CMC) of F127 is about 0.26-0.8 wt% so that the utility of F127 in nano-technology based drug delivery system is limited since the nano-sized micelles could dissociate upon dilution. Herein, stearic acid (SA) was simply coupled to F127 between the carboxyl group of SA and the hydroxyl group of F127, which formed a novel copolymer named as SA-coupled F127, with significantly lower CMC. Above the CMC 6.9 × 10(-5)wt%, SA-coupled F127 self-assembled stable nanoparticles with Zeta potential -36 mV. Doxorubicin (DOX)-loaded nanoparticles were made, with drug loading (DL) 5.7 wt% and Zeta potential -36 to -39 mV, and the nanoparticles exhibited distinct shape with the size distribution from 20 to 50 nm. DOX-loaded nanoparticles were relatively stable and exhibited DOX dependant cytotoxicity toward MCF-7 cells in vitro. These results suggest that SA-coupled F127 potentially could be applied as a nano-technology based drug delivery method.     

Comparative effects of different cosurfactants on sterile prednisolone acetate ocular submicron emulsions stability and release

Pluronic F68 is a nonionic, thermogelling block copolymer showing a high dehydration resistance during autoclaving due to its high cloud point (>100 °C). Tween 80 (with cloud point of 72.5 °C), is a polyoxyethylene-based cosurfactant, susceptible to temperature because of a decrease in its solubility by temperature increase. This study was done to explore whether or not, when compared with Tween 80, Pluronic F68 could be used blindly as a suitable cosurfactant for the preparation of terminally sterilized ocular submicron emulsions containing a lipid soluble drug, prednisolone acetate (PA). Various oils of variable viscosities were also tried. The results proved that no prediction can be made based on previously known physico-chemical properties alone and that emulsion stability depends on the contribution of the various emulsion components including: oil, surfactant and cosurfactant, in addition to the drug properties.     

Synthesis and Characterization of pH- and Temperature-sensitive Hydrogels of Poly (Styrene-alt-Maleic Anhydride)-co-Pluronic for Drug Release

A pH- and temperature-sensitive hydrogel of poly(styrene-alt-maleic anhydride) -co-Pluronic P123 (PSMA-P123) was prepared by the reaction of anhydride groups (MA) on PSMA with the hydroxyl groups on Pluronic (triblock polyethylene oxide-co-polypropylene oxide-co-polyethylene oxide, HO(CH₂CH₂O)₂₀(CH₂CH(CH₃)O)₇₀ (CH₂CH₂O)₂₀OH). The effect of proportions between PMSA and P123 on the gel fraction was determined. The effects of pH value and temperature on swelling ratio of the hydrogels were evaluated. Scanning electron microscopy was used to observe the morphology of the hydrogels. Differential scanning calorimetry was employed to characterize the thermo-sensitivity of the hydrogel. The drug-release behavior of the hydrogels was investigated by using chloromycetin as a model drug. The effect of temperature and pH on the release of chloromycetin from the hydrogels was studied. These results showed that PSMA-P123 hydrogels, being pH- and temperature-sensitive and reversible, appeared to be of potential for biomedical materials, especially for drug release applications.     

Characterizing the impact of thermal gels on isotachophoresis in microfluidic devices

Thermally reversible Pluronic gels have been employed as separation matrices in microfluidic devices in the analysis of biological macromolecules. The phase of these gels can be tuned between liquid and solid states using temperature to vary fluidic resistance and alter peak resolution. Although separations in thermal gels have been characterized, their effect on isotachophoresis has not. This study used fluorescein as a model analyte to evaluate isotachophoretic preconcentration as a function of thermal polymer concentration and temperature. Results demonstrated that increasing polymer concentration in microfluidic channels increased the apparent analyte concentration. A critical minimum of 10% (w/v) Pluronic was required to achieve efficient preconcentration with maximum focusing occurring in 20 and 25% polymer gels. Temperature of the thermal gel also impacted analyte focusing. Most efficient focusing was achieved at 25°C with diminishing analyte accumulation at higher and lower temperatures. Under optimal conditions, isotachophoretic preconcentration increased an additional threefold simply by including thermal gels in the system. This approach can be readily implemented in other applications to increase detection sensitivity and measure low-concentration analytes within simple microfluidic devices.     

Temperature Dependence in the Synthesis of SBA-16-Type Mesoporous Silica with Pluronic F68 Block Copolymer

By adjusting the local effective surfactant packing parameter through synthesis temperature, highly ordered SBA-16-type mesoporous silica materials have been synthesized by templating with a nonionic triblock copolymer Pluronic F68 in strongly acidic conditions at temperature 30～40°C with the addition of K₂SO₄. The prepared SBA-16-type mesoporous silica materials having Im3m cubic mesostructure were proved by the well-defined x-ray diffraction patterns combined with transmission electron microscopy. Scanning electron microscopy indicated that a transformation from faced-sphere to faced-polyhedron shape morphologies could be induced with increasing of the synthesis temperature. The nitrogen adsorption–desorption analysis revealed that the mean pore size (5.50～6.13 nm) of the prepared materials increased with increasing synthesis temperature. However, when the synthesis temperature exceeded 46°C, only disordered mesoporous silca was obtained. Our synthesis strategies by adjusting the local effective surfactant packing parameter through synthesis condition, even in a narrow range, would be used not only to optimize the synthesis conditions of reported mesoporous silca, but also to fabricate new mesoporous silica materials with well-ordered channel and anticipated morphologies.