A cyclic brush zwitterionic polymer based pH-responsive nanocarrier-mediated dual drug delivery system with lubrication maintenance for osteoarthritis treatment

Enhanced joint synergistic lubrication combined with anti-inflammatory therapy is an effective strategy to delay the progression of early osteoarthritis (OA) but has been rarely reported. The hydration lubrication of zwitterions and inherent super-lubrication properties of the cyclic brush, as well as the enhancement of the steric stability of the cyclic topology, can effectively improve the drug loading and utilization; herein we report a pH-responsive cyclic brush zwitterionic polymer (CB) with SBMA and DMAEMA as brushes and a cyclic polymer (c-P(HEMA)) as the core template, possessing a low coefficient of friction (0.017). After loading with hydrophobic curcumin and hydrophilic loxoprofen sodium it demonstrates high drug-loading efficiency. In vitro and in vivo experiments confirmed the triple function of the CB on superlubrication, sequence controlled release and anti-inflammatory effects demonstrated by Micro CT, histological analysis and qRT-PCR. Overall, the CB is a promising long-acting lubricating therapeutic agent, with potential for OA treatment or other diseases.