High Loading, Reversible Disulfide Core-Cross-Linked Multifunctional Micelles for Triggered Release of Camptothecin
2018
Nanomedicines in polymeric therapeutics present a potential treatment for cancers. However, their clinical effectiveness still has room to be improved. Herein, reduction-responsive reversibly core-cross-linked micelles based on the poly(ethylene glycol)-dihydrolipoic acid (MeO-PEG2k-DHLA) conjugate were developed for triggered intracellular release of camptothecin (CPT). Coupling two molecules of dihydrolipoic acid (DHLA) to methyl-terminated PEG (Mw 2000) through a labile ester bond was performed by solution-phase condensation reactions. Due to the amphiphilic property, MeO-PEG2k-DHLA conjugate formed micelles that were readily cross-linked with disulfide formation dispersed in water. These sole cross-linked micelles were 74.9 nm in hydrodiameter, as analyzed by dynamic light scattering (DLS). The nanostructures demonstrated excellent stability against extensive dilution, while rapidly dissociated under 10 mM glutathione (GSH), highlighting their potential for drug delivery. Interestingly, CPT was modifi...
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