A novel redox-responsive ursolic acid polymeric prodrug delivery system for osteosarcoma therapy. (1st January 2021)

• Record Type: Journal Article
• Authors: Fu, Daijie; Ni, Zhe; Wu, Kerong; Cheng, Peng; Ji, Xiaofeng; Li, Guoyuan; Shang, Xifu
• Is Part Of: Drug delivery. Volume 28:Number 1(2021)
• Page Start: 195
• Page End: 205
• Publication Date: 2021-01-01
• Subjects: Ursolic acid -- redox-responsive -- pH-responsive -- polymeric prodrug -- micelles -- osteosarcoma; Drug delivery systems -- Periodicals; Drug targeting -- Periodicals; 615.05
• DOI: 10.1080/10717544.2020.1870583
• Languages: English
• ISSNs: 1071-7544

Abstract

Abstract: Ursolic acid (UA), found widely in nature, exerts effective anti-tumoral activity against various malignant tumors. However, the low water solubility and poor bioavailability of UA have greatly hindered its translation to the clinic. To overcome these drawbacks, a simple redox-sensitive UA polymeric prodrug was synthesized by conjugating UA to polyethylene glycol using a disulfide bond. This formulation can self-assemble into micelles (U-SS-M) in aqueous solutions to produce small size micelles (∼62.5 nm in diameter) with high drug loading efficiency (∼16.7%) that exhibit pH and reduction dual-sensitivity. The cell and animal studies performed using the osteosarcoma MG-63 cell line and MG-63 cancer xenograft mice as the model systems consistently confirmed that the U-SS-M formulation could significantly prolong the circulation in blood and favor accumulation in tumor tissue. Targeted accumulation allows the U-SS-M to be effectively internalized by cancer cells, where the rapid release of UA is favored by a glutathione-rich and acidic intracellular environment, and ultimately achieves potent antitumor efficacy.