Self-assembled micelles stabilized by covalent α-lipoic acid-carboxymethyl chitosan conjugates: Enabling stable delivery and glutathione-responsive release of coenzyme Q10.

Coenzyme Q10 (CoQ10) participates in and maintains the mitochondrial respiratory chain, serving as an essential antioxidant in the human body. In this study, an advanced delivery system was developed to address the poor stability, lack of targeted release specificity, and low bioavailability of CoQ10. Disulfide bonds (S-S) were incorporated into the delivery system to enhance CoQ10 stability and enable triggered release in pathological microenvironments, thereby improving its bioavailability and bioactivity. The delivery system was constructed from an amphiphilic copolymer consisting of carboxymethyl chitosan and α-lipoic acid at a 1:1 molar ratio (CMCS-LA), which was driven by both amide and ester bonds. An ultrasound-assisted method was used to create self-assembled CoQ10-loaded micelles. These CoQ10-loaded micelles were relatively small spheroidal particles (≈ 600 nm) with excellent water dispersibility and high encapsulation efficiency (≈ 80%) for CoQ10. The delivery system enhanced the photothermal stability, gastrointestinal stability, and bioaccessibility of CoQ10, as well as increased its free radical-scavenging activity. In simulated pathological microenvironments with high reduced glutathione concentration, the micelles rapidly released CoQ10 via S-S cleavage. In summary, we successfully developed an advanced colloidal delivery system for CoQ10, which significantly increased its dispersibility, stability, bioaccessibility, and bioactivity.