Facile fabrication of poly(acrylic acid) coated chitosan nanoparticles with improved stability in biological environments

Chitosan is one of the most important and commonly used natural polysaccharides in drug delivery for its biocompatible and biodegradable properties. However, poor blood circulation of the chitosan nanoparticles due to their cationic nature is one of the major bottlenecks of chitosan-based drug delivery systems. To address this problem, a versatile platform based on poly(acrylic acid) (PAA) coated ionically cross-linked chitosan/tripolyphosphate nanoparticles (CTS/TPP-PAA NPs), is reported. The zeta potentials of CTS/TPP and CTS/TPP-PAA NPs are approximately 33   mV and −25   mV, respectively. CTS/TPP NPs quickly aggregate in PBS (phosphate buffered saline) and DMEM (Dulbecco’s modified Eagle’s medium). Conversely, CTS/TPP-PAA NPs exhibit excellent colloidal stability in plasma solution for more than 24   h. The PAA coating also endows CTS/TPP-PAA NPs with decreased protein adsorption capacity and improved buffering capacity. More importantly, the residual carboxyl and amino groups on CTS/TPP-PAA NPs provide abundant reactive sites for further functional modifications. Therefore, the CTS/TPP-PAA NPs reported here may be useful as an alternative drug delivery system.