Preparation and cytotoxicity evaluation of folic acid-modified YF8-OA self-assembled lipid prodrug nanoparticles

• Published in: Pharmaceutical development and technology Vol. 28; no. 5; p. 452
• Main Authors: Li, Fu, Yang, Fangfang, Guan, Chenxi, Wei, Pengcheng, He, Dongqiong, Li, Qingwen, Wang, Lisheng, Yuan, Mingqing
• Format: Journal Article
• Language: English
• Published: England 28.05.2023
• Subjects: Antineoplastic Agents - chemistry; Drug Delivery Systems - methods; Folic Acid - chemistry; HeLa Cells; Humans; Lipopolysaccharides; Nanoparticles - chemistry; Oleic Acid; Prodrugs - chemistry; Prodrugs - pharmacology; Matrine derivative YF8; lipid prodrug nanoparticles (LPs); drug release; folic acid; cytotoxicity
• ISSN: 1097-9867
• DOI: 10.1080/10837450.2023.2206487

This study aimed to improve the use of YF8, a matrine derivative obtained through chemical transformation of matrine extracted from . YF8 has demonstrated improved cytotoxicity compared to matrine, but its hydrophobic nature hinders its application. To overcome this, the lipid prodrug YF8-OA was synthesized by linking oleic acid (OA) to YF8 through an ester bond. Although YF8-OA could self-assemble into unique nanostructures in water, it was not sufficiently stable. To enhance the stability of YF8-OA lipid prodrug nanoparticles (LPs), we employed the strategy of PEGylation using DSPE-mPEG or DSPE-mPEG conjugated with folic acid (FA). This resulted in the formation of uniform spherical nanoparticles with greatly improved stability and a maximum drug load capacity upto 58.63%. Cytotoxicity was evaluated in A549, HeLa, and HepG2 cell lines. The results showed that in HeLa cells, the IC value of YF8-OA/LPs with FA-modified PEGylation was significantly lower than that of YF8-OA/LPs modified by PEGylation alone. However, no significant enhancement was observed in A549 and HepG2 cells. In conclusion, the lipid prodrug YF8-OA can form nanoparticles in aqueous solution to address its poor water solubility. Modification with FA resulted in further enhanced cytotoxicity, providing a potential avenue for exerting the antitumor activity of matrine analogs.