Release of quercetin from micellar nanoparticles with saturated and unsaturated core forming polyesters — A combined computational and experimental study

Computational and experimental studies were combined to obtain new insight into the widely reported anomalous release mechanism of hydrophobic drug (quercetin) from polymeric micellar nanoparticles. Saturated and unsaturated amphiphilic triblock copolymers from monomethoxy polyethylene glycol (mPEG), poly(butylene adipate) (PBA) and poly(cis-2-butene adipate) (PCBA) (mPEG-PBA-mPEG and mPEG-PCBA-mPEG) were utilized as model polymers to specify the contribution of polymer-micelle degradation and polymer–drug interactions on the observed differences in the release rates by applicable computational investigation and experimental evaluations. Monitoring the size of the micelles through the releasing process together with hydrolytic degradation studies of the core forming polymers proved that the contribution of polymer hydrolysis and micelle degradation on the observed differences in the release rates during the release time window was minimal. The compatibility between quercetin and the core forming polymer is another factor influencing the drug encapsulation and the relative release rate and it was therefore investigated theoretically (using density functional theory (DFT) at B3LYP/6-311++G level of theory) and experimentally (FT-IR imaging). The drug–polymer interactions in the core were shown to be much more important than the polymer and/or micelle swelling–dissociation–degradation processes under the studied conditions.