pH-Responsive polymers

We present an overview of existing theories of block polymer micelles. We focus here on the equilibrium structure of nanoaggregates formed by solvophobic/solvophilic diblock copolymers in a dilute solution and briefly address the association behavior of triblock terpolymer. We outline recent advances in the field and some challenging problems for theoretical developments.

Theory of Block Polymer Micelles: Recent Advances and Current Challenges

In this article, we highlight some recent developments in "smart" physical hydrogels achieved by self-assembling of block type macromolecules. More precisely we focus on two interesting types of gelators namely conventional ionic (or ionogenic) block copolymers and peptide-based polymers having as a common feature their responsiveness to pH and/or temperature which are the main triggers used for potential biomedical applications. Taking advantage of the immense skills of conventional block copolymer hydrogelators, namely macromolecular design, self-assembling mechanism, gel rheological properties, responsiveness to various triggers and innovative applications, the development of novel self-assembling gelators, integrating the new knowledge emerging from the peptide-based systems, opens new horizons towards bio-inspired technologies.

Recent trends in pH/thermo-responsive self-assembling hydrogels: from polyions to peptide-based polymeric gelators

A novel type of amphiphilic ionic copolymer comprising a hydrophilic poly(acrylic acid) (PAA) block and an amphiphilic poly(acrylic acid)-grad-poly(styrene) (PAA-grad-PS) copolymer block was synthesized using a one step direct nitroxide-mediated polymerization (NMP). A strong influence of the macroinitiator on the values of the reactivity ratios of the co-monomers is confirmed by 1H NMR. The aggregation behaviour of the copolymers in the aqueous medium was studied by small-angle neutron scattering (SANS) and dynamic light scattering (DLS) and by transmission electron microscopy (TEM) in a wide range of pHs and ionic strengths. It has been demonstrated that PAA-b-(PAA-grad-PS) copolymers are soluble in alkaline water at room temperature without the special experimental procedures (addition of co-solvent, heating, etc.) that are usually required for solubilisation of classical PAA-b-PS diblock copolymers. The self-assembly of the PAA-b-(PAA-grad-PS) copolymers into nano-scale aggregates at low/moderate pH and/or high ionic strength was demonstrated by SANS and DLS experiments. The SANS spectra for the copolymer solution exhibit a correlation peak pointing to the formation of micelles with repulsive coronae. TEM images indicate that the micelles have an approximately spherical shape and exhibit a wide size distribution. Our results prove, that in contrast to “frozen” aggregates formed by PAA-b-PS copolymers in aqueous media, the micelles of PAA-b-(PAA-grad-PS) amphiphilic copolymers exhibit “dynamic” pH-responsive properties, i.e. they can reversibly change their aggregation number upon a variation in the pH or salinity of the solution.

Synthesis and pH- and salinity-controlled self-assembly of novel amphiphilic block-gradient copolymers of styrene and acrylic acid

Introduction: Smart hydrogel systems present opportunities to not only provide hydrophobic molecule encapsulation capability but to also respond to specific delivery routes.Areas covered: An overview of the design principles, preparation methods and applications of hydrogel systems for delivery of hydrophobic drugs is given. It begins with a summary of the advantages of hydrogels as delivery vehicles over other approaches, particularly macromolecular nanocarriers, before proceeding to address the design and preparation strategies and chemistry involved, with a particular focus on the introduction of hydrophobic domains into (naturally) hydrophilic hydrogels. Finally, the applications in different delivery routes are discussed.Expert opinion: Modifications to conventional hydrogels can endow them with the capability to carry hydrophobic drugs but other functions as well, such as the improved mechanical stability, which is important for long-term in vivo residence and/or self-healing properties usef...

Hydrogels with smart systems for delivery of hydrophobic drugs

We demonstrate the possibility of reversible pH-controlled sol–gel transition in aqueous solution of associating amphiphilic triblock copolymer poly(styrene-grad-acrylic acid)-b-poly(acrylic acid)-b-poly(styrene-grad-acrylic acid), (PS-grad-PAA)-b-PAA-b-(PS-grad-PAA), synthesized vianitroxide-mediated (NM) radical copolymerization. The presence of pH-sensitive co-monomer units of the acrylic acid in the terminal blocks ensures the dynamic nature of the styrene-rich hydrophobic nano-domains which are formed at low pH. At small polymer concentrations the association triggered by lowering the pH gives rise to flower-like micelles stabilized by partially ionized PAA coronae. The pH-controlled association was monitored by DLS-titration and manifested in the evolution of a correlation peak in the SANS spectra. The resulting copolymer aggregates were visualized by TEM, which confirmed the spherical shape of the dense styrene-rich domains. Above the micelle overlap concentration a decrease in pH provokes macroscopic gelation. Here the styrene-reach domains perform as cross-links in the transient network. The pH-triggered sol-to-gel transition is manifested in an abrupt and strong (up to 3 orders of magnitude) increase in the zero-shear viscosity and in a characteristic change in the frequency dependence of the storage and loss moduli. The discovered effect can be used for efficient pH-control of the rheological properties of aqueous solutions.

Z.c. Bakaeva

Papers

Synthesis and pH- and salinity-controlled self-assembly of novel amphiphilic block-gradient copolymers of styrene and acrylic acid

pH-triggered reversible sol–gel transition in aqueous solutions of amphiphilic gradient copolymers