Chitosan-based bone-targeted nanoparticles delivery of cyclolinopeptide J for the synergistic treatment of osteoporosis.

Abstract

The chitosan-based bone-targeted delivery system was designed to enhance the therapy efficacy of Cyclolinopeptide J (CLJ), a bioactive peptide derived from flaxseed, for the treatment of osteoporosis. The bone-targeting polymer conjugates (CSD8) were prepared via a crosslinking reaction between carboxylated chitosan (CMCS) and functional peptide (ASP8). The CSD8 was then modified on the surface of CLJ-loaded nanoparticles to form novel nanoparticles (JCA/CSD8). The particle size of JCA/CSD8 was 122.40 ± 1.8 nm and the loading capacity of CLJ was 22.7 %. The results showed that the in vitro bone affinity and in vivo bone targeting efficiency of JCA/CSD8 increased 11.7-fold and 13.6-fold, respectively, achieving systemic targeting. Moreover, in vitro studies revealed that JCA/CSD8 could degrade within lysosomes under acidic conditions, thereby releasing CLJ and Ca²⁺ for synergistically promoting osteogenesis to realize the local targeting. The JCA/CSD8 group increased the transcription levels of osteogenic-related markers, including OPG, ColI, OCN, OPN, RUNX2, and ALP. Furthermore, in vivo studies demonstrated the impressive capability of JCA/CSD8 to increase bone density and restore trabecular bone architecture in the OVX mice model, which was superior to the positive control group. In conclusion, using chitosan-based bone-targeted nanoparticles presents a highly promising and efficient clinical therapy for addressing osteoporosis.