Francisco Fernández-Trillo

Synthetic polymers for biopharmaceutical delivery

The increasing complexity of biological molecules being developed for medical applications requires more sophisticated carrier materials to take these potent but delicate therapeutics to in vivo targets. Recent advances in polymer synthesis chemistries are enabling carrier vehicles of greater sophistication in architecture and function to be prepared. In this outline review, the application of polymer chemistries to protein and nucleic acid therapeutics are considered.

Directed Assembly of Inorganic Polyoxometalate‐based Micrometer‐Scale Tubular Architectures by Using Optical Control

Go with the flow: Laser-induced flow patterns are used to direct the self-assembly of dissolved inorganic polyoxometalate clusters into robust, hollow tubular networks and micro-materials (see picture; scale bar: 500u2005μm) in real time. The hollow nature of these materials can be exploited to develop devices in which the self-assembled tubes act as microscopic flow channels.

Synthetic Polymers for Simultaneous Bacterial Sequestration and Quorum Sense Interference

Double agents: dual-action polymers are able to sequester rapidly the marine organism Vibrio harveyi from suspension, while at the same time quenching bacterial quorum sense (QS) signals. The potency of the polymers is assessed by cell aggregation experiments and competitive binding assays against a QS signal precursor, and their effect on bacterial behavior is shown by means of bioluminescence.

Dually sensitive dextran-based micelles for methotrexate delivery

Temperature-sensitive polymeric micelles were prepared from dextran grafted with poly(N-isopropylacrylamide) (PNIPAAm) or polyethylene glycol methyl ether (PEGMA) via controlled radical polymerization and evaluated as delivery systems of the anticancer drug methotrexate (MTX). Polymer-grafting was carried out after introduction of initiating groups onto the polysaccharide backbone, without the need for protection of hydroxyl groups and avoiding the use of toxic solvents. Temperature-responsive dextran-based copolymers were designed to exhibit self-aggregation behaviour, affinity for MTX and high cellular internalization. In addition, some grafted polymers incorporated 2-aminoethyl methacrylate to reinforce MTX encapsulation in the micelles by means of ionic interactions. Dextran-based micelles were cytocompatible and had an appropriate size to be used as drug carriers. MTX release was dependent on the pH and temperature. The combination of poly(2-aminoethylmethacrylate) and PNIPAAm with the dextran backbone permitted the complete release of MTX at normal physiological temperature. Co-polymer micelles were highly internalized by tumour cells (CHO-K1) and, when loaded with MTX, led to enhanced cytotoxicity compared to the free drug.

Well-defined polymeric vesicles with high stability and modulation of cell uptake by a simple coating protocol

Amphiphilic polymers have been synthesised by controlled free radical polymerisation techniques. These polymers self-assemble into well-defined vesicles in aqueous conditions, enabling encapsulation of a model hydrophilic molecule. The polymeric vesicles show high stability against a range of aqueous conditions with marginal release of cargo, even in the presence of known cell-membrane disruptive polymers such as branched poly(ethylene imine) (b-PEI). This stability allows for inversion of the surface charge of the polymeric vesicles by a simple coating protocol leading to an enhanced uptake by mammalian cells.