Reduction‐Sensitive Self‐Aggregates as a Novel Delivery System

Abstract

Abstract Methoxy PEG amine with molecular weight of 5k and ε ‐caprolactone with molecular weight of 1 960 were conjugated to a peptide comprising three cysteine residues. The shift of peak molecular weight and narrow molecular weight distribution in GPC trace without any noticeable shoulder as well as 1 H NMR analysis confirmed the successful synthesis of the copolymer. A modified O/W dialysis system was employed to prepare self‐aggregates having the size around 210 nm. During the dialysis, stabilized aggregates were obtained by intermolecular disulfide bonds via oxidation. Critical aggregate concentration (CAC) of the copolymer was determined as 0.07 mg · mL −1 and disulfide‐stabilized self‐aggregates remained stable regardless of the concentration without displaying CAC. Doxorubicin‐loading amount and efficiency was 8.7 and 26.0%, respectively. Release profile of doxorubicin below CAC at 37 °C showed a sustained release and the addition of D , L ‐dithiothreitol (DTT) after 24 h triggered a burst release of doxorubicin. Intermolecular disulfide bonds via oxidation stabilized the polymeric aggregates even in the diluted condition similar to that in the bloodstream and addition of DTT destabilized the aggregates to burst encapsulated doxorubicin in the reductive condition. magnified image