Enzymatic synthesis of unique PEG-free copolymers and their application in biomedical fields

Drugs that are poorly water-soluble present a critical bottleneck in the implementation of new therapeutic treatments, with 90% of drugs in development being classed as such. Adequate aqueous drug solubility is vital to achieving desired therapeutic drug concentration and generate a pharmacological response.

Aliphatic, biodegradable polyesters are of particular interest due their ability to be hydrolysed in vivo - making them ideal for biodegradable drug delivery systems (DDS). Furthermore, aliphatic polyesters have shown great potential in nanomaterial DDS through encapsulation of the drug within a polymeric nanoparticle matrix. However, the limited choice of commercially available, biodegradable polyesters remains a critical limitation. The biomedical industry relies heavily on unfunctionalised polyesters, namely polylactic acid in medical devices, and polyglycolide used in sutures, whilst amphiphilic block copolymers such as poly(ethylene glycol)-polycaprolactone are used due to their ability to self-assemble.

PEG and its copolymers (in particular with aliphatic polyesters) are used extensively in drug delivery/nanotechnology due to so called "stealth behaviour". 'PEGylated' systems increase retention time therapeutics in the bloodstream to improve long-term systemic circulation and bioavailability through avoidance of opsonization. To date, the majority of the polymeric nanomedicine drug products that have been approved by the FDA contain PEG. Despite PEG's vast usage, there are a several drawbacks: it is non-biodegradable in vivo; there are increasing reports of PEG hypersensitivity; PEG has limited chemical functionality and finally, PEG is fossil-derived which poses sustainability concerns.

Evidently there is a need to develop biodegradable PEG-alternatives that improve therapeutic water solubility. Therefore, replacing PEG with bioresourcesed polyols in copolymer systems is a promising strategy to produce functionalised polyesters for biomedical applications.
The project aims to create novel polyesters by combining a range of mechanisms (ring opening/polycondensation) with tuneable microstructure and physiochemical properties, for drug delivery applications.

Enzymatic catalysis provides a controlled route towards such polyesters. Not only are biocatalysts regio- and chemo selective, their use employs mild, low energetically demanding synthesis. Furthermore, the use of bio-derived monomers ensures a more sustainable process.