A "Trojan Horse" Strategy: The Preparation of Bile Acid-Modifying Irinotecan Hydrochloride Nanoliposomes for Liver-Targeted Anticancer Drug Delivery System Study

• Published in: Molecules (Basel, Switzerland) Switzerland), 2023-02, Vol.28 (4), p.1577
• Main Authors: Zhou, Tao, Liu, Yushi, Lei, Kelu, Liu, Junjing, Hu, Minghao, Guo, Li, Guo, Yiping, Ye, Qiang
• Format: Article
• Language: English
• Subjects: Acids; Analysis; Animals; Antineoplastic Agents; Bile; Bile acids; Bile Acids and Salts; Cancer therapies; Carcinoma, Hepatocellular; Cholesterol; Cholic acid; Cholic Acids; Colorectal cancer; Drug delivery; Drug Delivery Systems; Drug dosages; Drugs; Encapsulation; Hepatocellular carcinoma; Hepatocytes; High performance liquid chromatography; Intestine; Irinotecan; irinotecan hydrochloride; Ligands; Liposomes; Liposomes - chemistry; Liquid chromatography; Liver; Liver cancer; Liver Neoplasms; Mice; Nanoparticles; Particle size; Permeability; Physiological aspects; Polypeptides; Protein transport; Proteins; Small intestine; Spyware; targeted modification; Toxicity; Transportation systems; Tumors; Vehicles; “Trojan Horse” Strategy
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules28041577

The bile acid transport system is a natural physiological cycling process between the liver and the small intestine, occurring approximately 6-15 times during the day. There are various bile acid transporter proteins on hepatocytes that specifically recognize bile acids for transport. Therefore, in this paper, a novel liposome, cholic acid-modified irinotecan hydrochloride liposomes (named CA-CPT-11-Lip), was prepared based on the "Trojan horse" strategy. The liposomes preparation process was optimized, and some important quality indicators were investigated. The distribution of irinotecan hydrochloride in mice was then analyzed by high-performance liquid chromatography (HPLC), and the toxicity of liposomes to hepatocellular carcinoma cells (HepG-2) was evaluated in vitro. As a result, CA-CPT-11-Lip was successfully prepared. It was spherical with a particle size of 154.16 ± 4.92 nm, and the drug loading and encapsulation efficiency were 3.72 ± 0.04% and 82.04 ± 1.38%, respectively. Compared with the conventional liposomes (without cholic acid modification, named CPT-11-Lip), CA-CPT-11-Lip had a smaller particle size and higher encapsulation efficiency, and the drug accumulation in the liver was more efficient, enhancing the anti-hepatocellular carcinoma activity of irinotecan hydrochloride. The novel nanoliposome modified by cholic acid may help to expand the application of irinotecan hydrochloride in the treatment of hepatocellular carcinoma and construct the drug delivery system mode of drug liver targeting.