Nanonization of andrographolide by a wet milling method: the effects of vitamin E TPGS and oral bioavailability enhancement

作者：Du, Ping^*; Jiang, Qikun; Yang, Rujie; Liu, Cuiru; Li, Yingchao; Wang, Liyuan; Xue, Peng; Fu, Qiang; Zhang, Tianhong^*

来源：RSC Advances, 2016, 6(103): 101404-101414.

DOI：10.1039/c6ra16002f

• SOLID LIPID NANOPARTICLES
• IN-VITRO CYTOTOXICITY
• INTESTINAL-ABSORPTION
• DRUG NANOCRYSTALS
• PARTICLE-SIZE
• FORMULATION
• PHARMACOKINETICS
• EXTRACT
• NANOSUSPENSIONS
• INHIBITION

Andrographolide (AND) has wide prospects in clinical use, but suffers from the restriction of poor oral bioavailability, due to its low solubility, rapid and extensive metabolism and efflux by P-glycoprotein (Pgp). In this study, for the first time, nanocrystals of AND, a model of BCS class II, were obtained via the wet milling method, with TPGS as a stabilizer to enhance the bioavailability of AND; HPMC E5 nanocrystals (E5NCs) were fabricated as the negative control. Using the optimized formulation, AND/TPGS nanocrystals (TNCs) and E5NCs were prepared. Physical characterizations demonstrated that the two nanocrystals shared similar particle size, the same crystallinity and identical morphology. Both nanocrystals were physically stable at 4 degrees C and 25 degrees C, respectively, for at least 1 month. Significant increases in cumulative dissolution (90% and 70%) were obtained after the TNCs and E5NCs dissolved at 60 min, which were higher than for coarse AND (no more than 40%), indicating that TNCs were superior to E5NCs in dissolution. As elucidated in the single-pass intestinal perfusion studies of AND, the nanocrystals could facilitate intestinal uptake, and TPGS possessed improved intestine absorption properties. Oral administration of AND nanocrystals produced a substantial improvement in oral absorption, compared to the AND coarse suspension. Compared to E5NCs, there was a significant difference in AUC(0-24h) after the oral administration of TNCs. Compared to the model group, the TNCs and E5NCs inhibited xylene induced ear swelling by 59.98 and 48.06%, respectively. These results corroborated that TNCs were a promising formulation choice for the oral delivery of AND.

• 出版日期2016
• 单位沈阳药科大学