Ding Dawei, Sun Bingjun, Cui Weiping, Chen Qin, Zhang Xuanbo, Zhang Haotian, He Zhonggui, Sun Jin, Luo Cong
Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China.
Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang 110042, China.
Asian J Pharm Sci. 2019 Sep;14(5):552-558. doi: 10.1016/j.ajps.2018.10.003. Epub 2018 Nov 20.
Self-nanoemulsifying drug delivery system (SNEDDS) has emerged as a promising platform to improve oral absorption of drugs with poor solubility and low permeability. However, large polarity molecules with insufficient lipid solubility, such as paclitaxel (PTX), would suffer from inferior formulation of SNEDDS due to poor compatibility. Herein, phospholipid-drug complex (PLDC) and SNEDDS were integrated into one system to facilitate oral delivery of PTX. First, PTX was formulated into PLDC in response to its inferior physicochemical properties. Then, the prepared PLDC was further formulated into SNEDDS by integrating these two drug delivery technologies into one system (PLDC-SNEDDS). After PLDC-SNEDDS dispersed in aqueous medium, nanoemulsion was formed immediately with an average particle size of ∼30 nm. Furthermore, the nanomulsion of PLDC-SNEDDS showed good colloidal stability in both HCl solution (0.1 mol/l, pH 1.0) and phosphate buffer solution (PBS, pH 6.8). , PTX-PLDC-SNEDDS showed distinct advantages in terms of oral absorption efficiency, with a 3.42-fold and 2.13-fold higher bioavailability than PTX-PLDC and PTX solution, respectively. Our results suggest that the integration of PLDC into SNEDDS could be utilized to facilitate the oral delivery of hydrophobic drugs with large polarity.
自纳米乳化药物递送系统（SNEDDS）已成为一种有前景的平台，可改善溶解度差和渗透性低的药物的口服吸收。然而，脂溶性不足的大极性分子，如紫杉醇（PTX），由于相容性差，其SNEDDS制剂效果不佳。在此，将磷脂-药物复合物（PLDC）和SNEDDS整合到一个系统中，以促进PTX的口服递送。首先，鉴于PTX较差的物理化学性质，将其制成PLDC。然后，通过将这两种药物递送技术整合到一个系统（PLDC-SNEDDS）中，将制备的PLDC进一步制成SNEDDS。PLDC-SNEDDS分散在水性介质中后，立即形成平均粒径约为30 nm的纳米乳液。此外，PLDC-SNEDDS的纳米乳液在盐酸溶液（0.1 mol/l，pH 1.0）和磷酸盐缓冲溶液（PBS，pH 6.8）中均表现出良好的胶体稳定性。PTX-PLDC-SNEDDS在口服吸收效率方面显示出明显优势，其生物利用度分别比PTX-PLDC和PTX溶液高3.42倍和2.13倍。我们的结果表明，将PLDC整合到SNEDDS中可用于促进大极性疏水药物的口服递送。
