Self-coacervation of carboxymethyl chitosan as a pH-responsive encapsulation and delivery strategy

Carboxymethyl chitosan (CMCS)-based complex coacervate has attracted much attention in drug oral delivery due to its pH-responsive property. As a unique ampholyte polymer, the self-coacervation of CMCS has great research potential. In this work, CMCS self-coacervates were prepared by adjusting the pH of the CMCS aqueous solution close to its isoelectric point. The Fourier-transformed infrared spectroscopy (FTIR) results revealed that electrostatic interactions, hydrogen bonding, and hydrophobic interactions were involved in the self-coacervation of CMCS. The obtained self-coacervates presented a dense surface structure, and were stable at a wide pH range of 3.0-6.0, and gradually dissolved under basic conditions. Although self-coacervation decreased the crystallinity and thermal stability of CMCS, the obtained coacervates showed excellent pH-responsive properties and ionic strength stability. We also investigated its potential in lactoferrin (LF) encapsulation and oral delivery. The CMCS self-coacervates exhibited a high encapsulation efficiency (EE) of 94.79 +/- 0.49% and loading capacity (LC) of 26.29 +/- 0.52% when the addition amount of LF was 2 mg. The simulated gastric digestion results demonstrated that CMCS self-coacervates could protect more than 80% of LF from hydrolysis and maintain the bioactivities of LF. Accordingly, the self-coacervation of CMCS could be used as a pH-responsive encapsulation and delivery strategy.