Glutathione Encapsulation in Core-Shell Drug Nanocarriers (Polymersomes and Niosomes) Prevents Advanced Glycation End-products Toxicities.

The clinical application of some natural molecules in therapy is usually limited due to the lack of feasible delivery systems. Core–shell nanocarriers (polymersomes and niosomes) are interesting stable nanocarriers that are biocompatible, biodegradable, and able to produce sustainable delivery. They can be modified and functionalized according to the application needed. In this report, we describe the synthesis of a smart and pH-responsive poly(ethylene oxide)-poly(lactide) polymersome (PEO-PL) and niosomes (NIO) loaded with GSH for efficient peptide delivery and potent application against advanced glycation end-products-related damages and toxicities. PEO-PL was constructed using the one-pot sequential anionic ring-opening polymerization method, while the niosomes were prepared via the thin film layer technique. The nanocarriers were characterized for their size and morphology by DLS and SEM. The formulations demonstrated a high encapsulation rate reaching 95% and showed increased sensitivity to release their content in acidic conditions (pH 5.5) compared with physiological media. PEO-PL showed a higher retention rate compared with the NIO. The nanocarriers showed no apparent toxicity even at high concentrations (400 µg/mL). The MTT test demonstrated that HeLa cell lines were more sensitive to GSH than U87 cell lines starting from 100 and 400 µg/mL, respectively. Testing the synthesized core–shell nanocarriers on altered proteins showed prolonged and high prevention rates of glycation, aggregation, and oxidation without hindering the effect of GSH. These bioresponsive nanocarriers appear as an interesting platform for biomedicine and therapy. [ABSTRACT FROM AUTHOR]