posted on 2017-08-30, 00:00authored byRa-Hye Kang, Ji-Yeong Kwon, Yeojin Kim, Sang-Min Lee
Chitosan
is a biocompatible natural polysaccharide, which has been
employed as a polymeric scaffold for versatile, systemic delivery
platforms and for locally injectable gels with temperature-sensitive
viscosity modulation. Despite the extensive investigation on the chemical
modification strategies, however, most of the chitosan-based delivery
platforms have been focused on the encapsulation of hydrophobic drugs,
which can be simply adsorbed on the chitosan scaffolds by hydrophobic
interaction via the postparticle-formation drug-loading process. Herein,
we present the facile formation of a cisplatin-coordinated chitosan
nanoplatform by exploiting the divalent metal (PtII)-mediated
conformational changes of chitosan chains, which allows for the simultaneous
drug-loading and nanoparticle formation. To this end, the native chitosan
has been chemically modified with short polyethylene glycol and malonic
acid as a colloidal stabilizer and a bidentate chelating ligand for
PtII coordination, respectively. The resulting PtII-modified polyampholytic chitosan (PtII-MPC) has been
self-associated in aqueous media by hydrophobic segregation into a
compact nanostructure, which exhibited an attenuated viscosity and
pH-sensitive release of PtII compounds. Once the cationic
drug molecules have been released under mild acidic conditions, the
neutralized PtII-free MPC undergoes interchain flocculation
near the isoelectric point because of the polyampholytic property,
possibly allowing for the facilitated endosomal escape during the
cellular endocytosis by the known membrane perturbation property of
chitosan.