Thiol-ene Reaction: An Efficient Tool to Design Lipophilic Polyphosphoesters for Drug Delivery Systems

Abstract

Poly(ethylene glycol)-b-polyphosphoester (PEG-b-PPE) block copolymer nanoparticles are promising carriers for poorly water soluble drugs. To enhance the drug loading capacity and efficiency of such micelles, a strategy was investigated for increasing the lipophilicity of the PPE block of these PEG-b-PPE amphiphilic copolymers. A PEG-b-PPE copolymer bearing pendant vinyl groups along the PPE block was synthesized and then modified by thiol-ene click reaction with thiols bearing either a long linear alkyl chain (dodecyl) or a tocopherol moiety. Ketoconazole was used as model for hydrophobic drugs. Comparison of the drug loading with PEG-b-PPE bearing shorter pendant groups is reported evidencing the key role of the structure of the pendant group on the PPE backbone. Finally, a first evidence of the biocompatibility of these novel PEG-b-PPE copolymers was achieved by performing cytotoxicity tests. The PEG-b-PPE derived by tocopherol was evidenced as particularly promising as delivery system of poorly water-soluble drugs.

Accelerating the end-to-end production of cyclic phosphate monomers with modular flow chemistry

“…Cytotoxicity assays of MeO-PEO-b-PEEP on bovine broblast cells and human umbilical vein endothelial cells revealed that no cytotoxic effects were observed for a concentration of up to 0.1 mg mL À1 of copolymer (see ESI, Section 2.5.12 †). These results are in agreement with data collected in a previous study regarding PEO-PPE diblock copolymers, 55 which paves the way for a potential biomedical application.…”

Antibacterial Efficacy of Silver or Arsenic Doped Polymer Composites Against Several Kinds of Bacteria

“…14 The first attempts to obtain phosphorus-containing polymers were made in the 1950s when scientists tried to mimic the properties of natural phosphorus-containing macromolecules. 15 To date, synthetic approaches to phosphorus-containing polyesters based on a number of monomers (PEG, lactic acid) have been developing, [16][17][18] which largely confirms the relevance of this task. Common methods for the synthesis of polyphosphoesters are polycondensation, transesterification, and ringopening polymerization.…”

Phosphorus and Silicon‐Based Macromolecules as Degradable Biomedical Polymers

“…[ 93 ] reported the synthesis of micelles for drug encapsulation based on PPE block copolymers by ROP and subsequent modification of the backbone by thiol‐yne click chemistry to create amphiphilic PPE polymers. A similar approach has been taken by Jerome et al., [ 94 ] who reported the synthesis of PEG‐PPE block copolymer self‐assembling nanoparticles for drug carrier systems. It was shown that the poorly water‐soluble drug ketoconazole could be encapsulated, thus increasing the concentration in aqueous systems.…”