Microgels with controlled network topologies by photocrosslinking-assisted continuous precipitation polymerization.

In this study, we present a new synthesis methodology based on photo-crosslinking-assisted continuous precipitation polymerization which allows controlling the distribution of crosslinks in microgels. In our approach we substituted conventional crosslinking agent by a comonomer carrying photo-crosslinkable 4-oxocyclopent-2-en-1-yl group. Microgel size, morphology, distribution of crosslinks and packing density of the polymer chains are studied as a function of retention time (Rt) in the flow reactor. Dynamic and static light scattering (DLS and SLS) as well as small angle X-ray scattering (SAXS) proved an excellent level of control over the distribution of crosslinks in microgels during the polymerization process. These results were confirmed by atomic force microscopy (AFM), indicating a difference in microgel stiffness and arrangement of the polymer network as resulting from increased Rt.

Polyelectrolyte-protein synergism: pH-responsive polyelectrolyte/insulin complexes as versatile carriers for targeted protein and drug delivery.

The co-assembly of polyelectrolytes (PE) with proteins offers a promising approach for designing complex structures with customizable morphologies, charge distribution, and stability for targeted cargo delivery. However, the complexity of protein structure limits our ability to predict the properties of the formed nanoparticles, and our goal is to identify the key triggers of the morphological transition in protein/PE complexes and evaluate their ability to encapsulate multivalent ionic drugs. A positively charged PE can assemble with a protein at pH above isoelectric point due to the electrostatic attraction and disassemble at pH below isoelectric point due to the repulsion. The additional hydrophilic block of the polymer should stabilize the particles in solution and enable them to encapsulate a negatively charged drug in the presence of PE excess. We demonstrated that diblock copolymers, poly(ethylene oxide)-block-poly(N,N-dimethylaminoethyl methacrylate) and poly(ethylene oxide)-block-poly(N,N,N-trimethylammonioethyl methacrylate), consisting of a polycation block and a neutral hydrophilic block, reversibly co-assemble with insulin in pH range between 5 and 8. Using small-angle neutron and X-ray scattering (SANS, SAXS), we showed that insulin arrangement within formed particles is controlled by intermolecular electrostatic forces between protein molecules, and can be tuned by varying ionic strength. For the first time, we observed by fluorescence that formed protein/PE complexes with excess of positive charges exhibited potential for encapsulating and controlled release of negatively charged bivalent drugs, protoporphyrin-IX and zinc(II) protoporphyrin-IX, enabling the development of nanocarriers for combination therapies with adjustable charge, stability, internal structure, and size.