Paclitaxel-loaded redox-sensitive nanoparticles based on hyaluronic acid-vitamin E succinate conjugates for improved lung cancer treatment

• Main Authors: Song Y, Cai H, Yin T, Huo M, Ma P, Zhou J, Lai W
• Format: Article
• Language: English
• Published: Dove Medical Press 2018-03-01
• Series: International Journal of Nanomedicine
• Subjects: tumor targeting; nanoparticles; redox-sensitive
• Online Access: https://www.dovepress.com/paclitaxel-loaded-redox-sensitive-nanoparticles-based-on-hyaluronic-ac-peer-reviewed-article-IJN

Yu Song,1,2 Han Cai,1 Tingjie Yin,1 Meirong Huo,1 Ping Ma,3 Jianping Zhou,1 Wenfang Lai2 1Department of Pharmaceutics, China Pharmaceutical University, Nanjing, People’s Republic of China; 2College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, People’s Republic of China; 3Formulation Development, Tolmar Inc, Fort Collins, CO, USA Background: Lung cancer is the primary cause of cancer-related death worldwide. A redox-sensitive nanocarrier system was developed for tumor-targeted drug delivery and sufficient drug release of the chemotherapeutic agent paclitaxel (PTX) for improved lung cancer treatment.Methods: The redox-sensitive nanocarrier system constructed from a hyaluronic acid-disulfide-vitamin E succinate (HA-SS-VES, HSV) conjugate was synthesized and PTX was loaded in the delivery system. The physicochemical properties of the HSV nanoparticles were characterized. The redox-sensitivity, tumor-targeting and intracellular drug release capability of the HSV nanoparticles were evaluated. Furthermore, in vitro and in vivo antitumor activity of the PTX-loaded HSV nanoparticles was investigated in a CD44 over-expressed A549 tumor model.Results: This HSV conjugate was successfully synthesized and self-assembled to form nanoparticles in aqueous condition with a low critical micelle concentration of 36.3 µg mL-1. Free PTX was successfully entrapped into the HSV nanoparticles with a high drug loading of 33.5% (w/w) and an entrapment efficiency of 90.6%. Moreover, the redox-sensitivity of the HSV nanoparticles was confirmed by particle size change of the nanoparticles along with in vitro release profiles in different reducing environment. In addition, the HA-receptor mediated endocytosis and the potency of redox-sensitivity for intracellular drug delivery were further verified by flow cytometry and confocal laser scanning microscopic analysis. The antitumor activity results showed that compared to redox-insensitive nanoparticles and Taxol®, PTX-loaded redox-sensitive nanoparticles exhibited much greater in vitro cytotoxicity and apoptosis-inducing ability against CD44 over-expressed A549 tumor cells. In vivo, the PTX-loaded HSV nanoparticles possessed much higher antitumor efficacy in an A549 mouse xenograft model and demonstrated improved safety profile. In summary, our PTX-loaded redox-sensitive HSV nanoparticles demonstrated enhanced antitumor efficacy and improved safety of PTX.Conclusion: The results of our study indicated the redox-sensitive HSV nanoparticle was a promising nanocarrier for lung cancer therapy. Keywords: tumor targeting, nanoparticles, redox-sensitive