Paclitaxel-loaded Nanoparticles of Cholanic Acid-Modified Hyaluronan Oligosaccharide for Tumor-site Specific Delivery

We have demonstrated that introduction of 5-beta-cholanic acid into low molecular weight hyaluronic acid oligosaccharide produces self-assembled nanoparticles with enhanced permeability to a tumor site in vivo. We have found that hyaluronic acid of molecular weight 16000 g/mol has appropriate injectable viscosity. For making self-assembled nanoparticles with the selected hyaluronic acid, the optimal degree of substitution value of cholanic acid was 14%, which was selected by considering the size and stability of nanoparticles after loading with paclitaxel. 30% paclitaxel was selected as the optimal feed amount to make the paclitaxel-loaded hyaluronic acid-cholanic acid nanoparticles. Importantly, the optimal formulation of paclitaxel-loaded nanoparticles showed less liver uptake than the reported formula, along with long circulation as well as tumor-site specific accumulation in the in vivo biodistribution study. In the antitumor efficacy study, the paclitaxel-loaded nanoparticles showed higher efficacy to inhibit tumor growth than a positive control in the breast cancer cell xenograft model.