Bioavailability enhancement of paclitaxel via a novel oral drug delivery system: paclitaxel-loaded glycyrrhizic acid micelles

• Published in: Molecules (Basel, Switzerland) Switzerland), 2015-03, Vol.20 (3), p.4337-4356
• Main Authors: Yang, Fu-Heng, Zhang, Qing, Liang, Qian-Ying, Wang, Sheng-Qi, Zhao, Bo-Xin, Wang, Ya-Tian, Cai, Yun, Li, Guo-Feng
• Format: Article
• Language: English
• Subjects: Acids; Administration, Oral; Animals; Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - pharmacokinetics; Antineoplastic Agents, Phytogenic - administration & dosage; Antineoplastic Agents, Phytogenic - pharmacokinetics; Bioavailability; Biological Availability; Drug Carriers; Drug Delivery Systems; Drug dosages; Drug Liberation; glycyrrhizic acid; Glycyrrhizic Acid - administration & dosage; Glycyrrhizic Acid - pharmacokinetics; Intestinal Absorption; Intestinal Mucosa - metabolism; Jejunum - metabolism; Male; Micelles; Oral administration; oral bioavailability; paclitaxel; Paclitaxel - administration & dosage; Paclitaxel - pharmacokinetics; Permeability; Pharmacokinetics; Rats; Rats, Sprague-Dawley; Tissue Distribution; Toxicity; Tumors
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules20034337

Paclitaxel (PTX, taxol), a classical antitumor drug against a wide range of tumors, shows poor oral bioavailability. In order to improve the oral bioavailability of PTX, glycyrrhizic acid (GA) was used as the carrier in this study. This was the first report on the preparation, characterization and the pharmacokinetic study in rats of PTX-loaded GA micelles The PTX-loaded micelles, prepared with ultrasonic dispersion method, displayed small particle sizes and spherical shapes. Differential scanning calorimeter (DSC) thermograms indicated that PTX was entrapped in the GA micelles and existed as an amorphous state. The encapsulation efficiency was about 90%, and the drug loading rate could reach up to 7.90%. PTX-loaded GA micelles displayed a delayed drug release compared to Taxol in the in vitro release experiment. In pharmacokinetic study via oral administration, the area under the plasma concentration-time curve (AUC0→24 h) of PTX-loaded GA micelles was about six times higher than that of Taxol (p < 0.05). The significant oral absorption enhancement of PTX from PTX-loaded GA micelles could be largely due to the increased absorption in jejunum and colon intestine. All these results suggested that GA would be a promising carrier for the oral delivery of PTX.