Effect of Hydrophilic Monomer Distribution on Self-Assembly of a pH-Responsive Copolymer: Spheres, Worms and Vesicles from a Single Copolymer Composition.

A series of copolymers containing 50 mol % acrylic acid (AA) and 50 mol % butyl acrylate (BA) but with differing composition profiles ranging from an AA-BA diblock copolymer to a linear gradient poly(AA-grad-BA) copolymer were synthesized and their pH-responsive self-assembly behavior was investigated. While assemblies of the AA-BA diblock copolymer were kinetically frozen, the gradient-like compositions underwent reversible changes in size and morphology in response to changes in pH. In particular, a diblock copolymer consisting of two random copolymer segments of equal length (16 mol % and 84 mol % AA content, respectively) formed spherical micelles at pH >5, a mix of spherical and wormlike micelles at pH 5 and vesicles at pH 4. These assemblies were characterized by dynamic light scattering, cryo-transmission electron microscopy and small angle neutron scattering.

All-Aqueous, Surfactant-Free, and pH-Driven Nanoformulation Methods of Dual-Responsive Polymer Nanoparticles and their Potential use as Nanocarriers of pH-Sensitive Drugs.

All-aqueous, surfactant-free, and pH-driven nanoformulation methods to generate pH- and temperature-responsive polymer nanoparticles (NPs) are described. Copolymers comprising a poly(methyl methacrylate) (PMMA) backbone with a few units of 2-(dimethylamino)ethyl methacrylate (DMAEMA) are solubilized in acidic buffer (pH 2.0) to produce pH-sensitive NPs. Copolymers of different molar mass (2.3-11.5 kg mol-1 ) and DMAEMA composition (7.3-14.2 mol%) are evaluated using a "conventional" pH-driven nanoformulation method (i.e., adding an aqueous polymer solution (acidic buffer) into an aqueous non-solvent (basic buffer)) and a robotized method for pH adjustment of polymer dispersions. Dynamic light scattering, zeta-potential (ζ), and sedimentation-diffusion analyses suggest the formation of dual-responsive NPs of tunable size (from 20 to 110 nm) being stable for at least 28 days in the pH and temperature intervals from 2.0 to 6.0 and 25 to 50 °C, respectively. Ultraviolet-visible spectroscopic experiments show that these NPs can act as nanocarriers for the pH-sensitive dipyridamole drug, expanding its bioavailability and potential controlled release as a function of pH and temperature. These approaches offer alternative strategies to prepare stimuli-responsive NPs, avoiding the use of harmful solvents and complex purification steps, and improving the availability of biocompatible polymer nanoformulations for specific controlled release of pH-sensitive cargos.

Automated Parallel Dialysis for Purification of Polymers.

The implementation of a dialysis method for the simultaneous purification of different polymer materials in a commercially available automated parallel synthesizer (APS) is discussed. The efficiency of this "unattended" automated parallel dialysis (APD) method was investigated by means of proton nuclear magnetic resonance (1H-NMR) measurements, which confirmed that the method enables the removal of up to 99% of the unreacted monomer derived from the synthesis of the corresponding polymers in the APS. Size-exclusion chromatography (SEC) revealed that the molar mass and molar mass distribution of the investigated polymers did not undergo significant changes after the application of the APD method. The method discussed herein can be regarded as a good alternative to the "unattended" and reliable purification of polymer libraries prepared in APS. This method may be useful for overcoming current limitations of high-throughput/-output (HT/O) synthesis of polymer libraries, where purification of the generated materials currently represents a significant constraint for establishing fully automated experimental workflows necessary to advance towards a full digitalization of research and development of new polymers for diverse applications.