Redox/pH-Responsive Biodegradable Thiol-Hyaluronic Acid/Chitosan Charge-Reversal Nanocarriers for Triggered Drug Release

Biodegradable nanoparticles and micelles are promising nanosystems for the targeted delivery of potent anticancer drugs. By using specialized polymers as nanocarriers, targeted drug delivery and release can be developed. We developed thiol-hyaluronic acid (HA-SH)/chitosan (CS) nanoparticles with redox/pH dual-responsiveness via electrostatic self-assembly followed by spontaneous chemical cross-linking. The nanoparticle surface charges were reversible through different HA-SH and CS mass ratios. Doxorubicin (DOX) was used as a model drug. Dual cross-linked nanoparticles with diameters of approximately 300 nm exhibited superior stability under physiological conditions compared with nanoparticles without disulfide cross-linking. DOX was loaded more efficiently into negative nanoparticles (45.7 wt%) than positive nanoparticles (14.2 wt%). Drug release from negative nanoparticles (zeta potential of approximately -20) was higher (87.8 wt%) at pH 4.5 and in the presence of 10 mM glutathione. Positive nanoparticles (zeta potential of approximately +20) showed the same trend, but the release rate was slower than that of negative nanoparticles. DOX-loaded HA-SH/CS particles were taken up by human breast cancer cells (SKBR3), and the loaded drug was released, exhibiting potential antitumor efficacy. The HA-SH/CS nanoparticles in this study were stable under physiological conditions and are promising candidates for the targeted delivery and release of anticancer drugs.