Wang Guanru, Xie Yaru, Qian Xindi, Zhang Xinyue, Shan Yanqiang, Zhang Minghui, Li Jie, Zhang Zhiwen, Li Yaping
State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
School of Pharmacy, Yantai University, Yantai, China.
Drug Dev Ind Pharm. 2022 Mar;48(3):109-116. doi: 10.1080/03639045.2022.2098316. Epub 2022 Jul 14.
The poor water solubility and inadequate oral bioavailability of gefitinib (Gef) remain a critical issue to achieve the therapeutic outcomes. Herein, we designed a poly(maleic anhydride-alt-1-octadecene) (PMA/C18) based lipid nanovehicle (PLN) to improve the intestinal absorption and oral bioavailability of poorly water-soluble Gef. PLN was nanometer-sized particles, and Gef was dispersed in the PLN formulation as amorphous or molecular state. At 4 h of oral administration, the tissue concentration of Gef in duodenum, jejunum, and ileum was profoundly enhanced 3.37-, 8.94-, and 8.09-fold by PLN when comparing to the counterpart lipid nanovehicle. Moreover, the oral bioavailability of Gef was significantly enhanced 2.48-fold by the PLN formulation when comparing to the free drug suspension. Therefore, this study provides an encouraging bioadhesive delivery platform to improve the oral delivery of poorly water-soluble drugs.
吉非替尼(Gef)较差的水溶性和口服生物利用度仍然是实现治疗效果的关键问题。在此,我们设计了一种基于聚(马来酸酐-alt-1-十八烯)(PMA/C18)的脂质纳米载体(PLN),以改善难溶性吉非替尼的肠道吸收和口服生物利用度。PLN为纳米级颗粒,吉非替尼以无定形或分子状态分散在PLN制剂中。口服给药4小时时,与相应的脂质纳米载体相比,PLN使吉非替尼在十二指肠、空肠和回肠中的组织浓度显著提高了3.37倍、8.94倍和8.09倍。此外,与游离药物混悬液相比,PLN制剂使吉非替尼的口服生物利用度显著提高了2.48倍。因此,本研究提供了一个令人鼓舞的生物黏附递送平台,以改善难溶性药物的口服递送。