Porous pH-responsive calcium alginate self-emulsifying gel microspheres as a multistage delivery system: Enhanced oral bioavailability of nintedanib via lymphatic absorption

Authors:
  • SHShiqi Huang
    Shiqi Huang
  • JCJiajing Che
    Jiajing Che
  • RPRui Pan
    Rui Pan
  • YLYehan Li
    Yehan Li
  • TYTian Yin
    Tian Yin
  • JGJingxin Gou
    Jingxin Gou
  • YWYanjiao Wang
    Yanjiao Wang
  • XTXing Tang
    Xing Tang
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Abstract
This study developed a liquid self-emulsifying drug delivery system (BIBF-SEDDS, size 23.83 nm, zeta 20.5 mV) to enhance nintedanib (BIBF) oral bioavailability. BIBF-SEDDS was encapsulated in pH-sensitive calcium alginate gel microspheres (BIBF-S-SEDDS). Eudragit L100 (precipitation inhibitor) and PEG 400 (porogenic agent) were further added to obtain porous BIBF-S-SEDDS. In vitro dissolution and in vivo pharmacokinetics in rats were compared with imitation soft capsules. Porous BIBF-S-SEDDS increased oral bioavailability by 2.11-fold, prolonged Tmax, reduced gastric irritation (HE staining), and improved intestinal absorption. Liver enzyme (ALT/AST) levels suggested better safety. A chylomicron blockade model indicated lymphatic transport as an auxiliary absorption pathway. Accelerated stability (6 months, 40°C/75% RH) showed no significant changes in appearance, drug content, or dissolution. This multistage delivery system offers a promising strategy for oral BIBF administration.