Guo Chen, Zhu Xichun, Yuan Haoyang, Liu Haoyu, Zhang Yu, Yin Tian, He Haibing, Gou Jingxin, Tang Xing
Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, Liaoning, People's Republic of China.
Center for Drug and Cosmetic Safety Evaluation and Research, Gansu Provincial Institute of Drug Control, 7 Yinan Road, Anning District, Lanzhou, 730070, Gansu, People's Republic of China.
AAPS PharmSciTech. 2022 Jun 10;23(5):163. doi: 10.1208/s12249-022-02308-7.
In recent years, the oral administration of vinorelbine has gradually replaced intravenous administration in the treatment of several types of tumors. Even though the risk of phlebitis is avoided with oral administration, oral vinorelbine is still not a highly patient-compliant route due to the severe gastrointestinal toxicity. Vinorelbine-loaded liposomes with high encapsulation efficiency and suitable particle size were prepared using the ammonium sulfate gradient method. Chitosan-coated liposomes showed the slowest in vitro release compared to uncoated liposomes and vinorelbine solution. No damage was observed in the intestinal epithelial cells of mice orally administered with coated vinorelbine liposomes due to the low presence of the free drug in the gastrointestinal tract and the LD was increased from 129.83 to 182.25 mg/kg compared to oral vinorelbine solution. In addition, the positive surface potential of chitosan-coating endowed liposomes with mucosal adhesive function, delaying the time to reach the peak plasma concentration of vinorelbine from 1 to 4 h after administration. And bioavailability was increased to 2.1-fold compared to vinorelbine solution. In short, a new strategy to address the severe gastrointestinal side effects of oral vinorelbine has been developed.
近年来，在几种肿瘤的治疗中，口服长春瑞滨已逐渐取代静脉给药。尽管口服给药可避免静脉炎风险，但由于严重的胃肠道毒性，口服长春瑞滨仍不是患者依从性很高的给药途径。采用硫酸铵梯度法制备了具有高包封率和合适粒径的长春瑞滨脂质体。与未包衣脂质体和长春瑞滨溶液相比，壳聚糖包衣脂质体的体外释放最慢。口服包衣长春瑞滨脂质体的小鼠肠道上皮细胞未观察到损伤，这是由于胃肠道中游离药物含量低，与口服长春瑞滨溶液相比，其半数致死量从129.83 mg/kg增加到182.25 mg/kg。此外，壳聚糖包衣的正表面电位赋予脂质体粘膜粘附功能，使长春瑞滨达到血浆浓度峰值的时间从给药后1小时延迟到4小时。与长春瑞滨溶液相比，生物利用度提高到2.1倍。简而言之，已开发出一种解决口服长春瑞滨严重胃肠道副作用的新策略。
