Divide and Comprehend: Separating the Effects of Hydrophobicity / Hydrophilicity and Crystallinity on the Thermal Properties of Polyester Based Drug Delivery SystemsPart of:
Biodegradable polymer nanoparticles (NPs) are of great interest for drug delivery systems due to their outstanding biocompatibility and easy preparation. The major challenge for these systems is to tailor their degradation and drug release to the application they are aimed for. It is reported that tuning the thermal properties (TPs) of polyesters via changing their crystallinity affects those properties but is also mostly accompanied by a variation of the hydrophilic / hydrophobic balance (HHB). This causes a knowledge gap on how the TPs of polymers affect their degradation and drug release without the influence of the HHB as third variable. In order to tackle that issue, our approach is to create novel polyester based NPs with different TPs, where the HHB is kept constant. Here we present first results of polymer synthesis and NP formation.
Polylactic acid (PLA) and a novel polymer “Poly Ethylene Glycolide” (PEtGly), with comparable structural features as PLA, as well as statistical copolymers PLA-co-EtGly with varying EtGly contents were synthesized by ring opening polymerization. Stereocomplexation was performed via casting method using tetrahydrofuran (THF). NPs in aqueous suspension were prepared by nanoprecipitation from THF into ultrapure water. The TPs were measured by differential scanning calorimetry (DSC). DLS was used to estimate the particle sizes of NPs and stereo complexes (SCs). NPs and SCs were characterized by AFM as well as with SEM and TEM. Pyrene fluorescence was used to determine the HHBs of PLA and PEtGly, which turned out to be the same. DSC measurements showed that the presence of EtGly significantly lowered both, the crystallinity of the copolymers compared to the homopolymers as well as the formation of SCs. AFM, SEM and TEM investigations of the NPs from copolymers, SCs and the bulk polymers consistently point towards a change of crystallinity induced by EtGly and an internal hollow structure of the NPs prepared via nanoprecipitation while the HHB is kept constant.
These polymeric NPs will lay the foundation for a new type of polymeric drug delivery systems which allows tailoring the degradation and release kinetics by changing their TPs.
This work is part of the Collaborative Research Center 1278: “Polytarget: Polymer-based nanoparticle libraries for targeted anti-inflammatory strategies” – project A06 which is funded by the Deutsche Forschungsgemeinschaft (DFG).