Efficient Intestinal Digestion and On Site Tumor-Bioactivation are the Two Important Determinants for Chylomicron-Mediated Lymph-Targeting Triglyceride-Mimetic Docetaxel Oral Prodrugs.

ABSTRACT: The oral absorption of chemotherapeutical drugs is restricted by poor solubility and permeability, high first-pass metabolism, and gastrointestinal toxicity. Intestinal lymphatic transport of lipophilic prodrugs is a promising strategy to improve the oral delivery efficiency of anticancer drugs via entrapment into a lipid formulation and to avoid first-pass metabolism. However, several basic principles have still not been clarified, such as intestinal digestibility and stability and on-site tumor bioactivation. Herein, triglyceride-mimetic prodrugs of docetaxel (DTX) are designed by conjugating them to the sn-2 position of triglyceride (TG) through different linkage bonds. The role of intestinal digestion in oral absorption of TG-like prodrugs is then investigated by introducing significan

SUBMITTER: Tian C 

PROVIDER: S-EPMC6918103 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature