Glycerol-Based Copolyesters as Polymeric Nanocarriers for Drug Delivery

Abstract

Enzymatic polymerization of glycerol-based polyesters has emerged as a selective and sustainable strategy for the production of degradable, amphiphilic, PEG-free polymeric materials. In the present work, we exploited the ability to produce copolyester variants of poly(glycerol adipate) (PGA), by adding a second functionalized diol in a one-pot fashion. The produced glycerol-based copolyesters, with a variety of amphiphilic balances and chemical functionalities along the backbone, have been screened as nanocarriers for drug delivery. The stability of the produced nanoparticles (NPs) was tested in relevant biological fluids and after freeze-drying treatment. The new variants outperformed PGA homopolymers in the penetration through a gel-like barrier as well as in their efficiency to encapsulate a poorly water-soluble model drug. All the tested polymeric NPs formulations have demonstrated biocompatibility in both in vitro and in vivo experiments, that utilize Caenorhabditis elegans nematodes. Taken together, these preliminary results highlight the importance of introducing new chemistry along polyester backbones while tuning the amphiphilic nature of the final polymers to improve the performance of NP systems.