Oral metronomic therapy of pancreatic cancer with gemcitabine and paclitaxel co-loaded in lecithin-based Self-Nanoemulsifying preconcentrate (LBSNEP)

Chien-Ju Lin; Wen-Ting Cheng; Ling-Chun Chen; Tzu-Ling Chen; Ming-Thau Sheu; Hong-Liang Lin

doi:10.1016/j.ijpharm.2023.123370

Oral metronomic therapy of pancreatic cancer with gemcitabine and paclitaxel co-loaded in lecithin-based Self-Nanoemulsifying preconcentrate (_LBSNEP)

Int J Pharm. 2023 Oct 15:645:123370. doi: 10.1016/j.ijpharm.2023.123370. Epub 2023 Sep 2.

Authors

Chien-Ju Lin¹, Wen-Ting Cheng², Ling-Chun Chen³, Tzu-Ling Chen⁴, Ming-Thau Sheu⁵, Hong-Liang Lin⁶

Affiliations

¹ School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address: mistylin@kmu.edu.tw.
² Department of Biotechnology and Pharmaceutical Technology, Yuanpei University of Medical Technology, Hsinchu, Taiwan. Electronic address: d301104004@tmu.edu.tw.
³ Department of Biotechnology and Pharmaceutical Technology, Yuanpei University of Medical Technology, Hsinchu, Taiwan. Electronic address: d8801004@mail.ypu.edu.tw.
⁴ School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan. Electronic address: m301108015@tmu.edu.tw.
⁵ School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan. Electronic address: mingsheu@tmu.edu.tw.
⁶ School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address: hlglin@kmu.edu.tw.

PMID: 37666310
DOI: 10.1016/j.ijpharm.2023.123370

Abstract

This study aimed to evaluate gemcitabine (GEM)/paclitaxel (PTX) co-loaded into a lecithin-based self-nanoemulsifying preconcentrate (_LBSNEP) orally administered in a metronomic therapeutic manner against pancreatic cancer. _LBSNEP was developed and evaluated, composed of Caproyl 90, Tween80, lecithin, TPGS, and propyl glycol at a ratio of 20:20:30:5:25, resulting in a droplet diameter of approximately 180 nm. Cell viability studies on MIA PaCa-2 demonstrated a synergetic effect at a proportion of 1:2 between PTX and GEM. Additionally, _LBSNEP and baicalein (BAI) were demonstrated to prevent GEM from being deaminated by cytidine deaminase. The combination of GEM, PTX, and BAI in the _LBSNEP showed good dissolution in simulated gastric fluid. The pharmacokinetic study conducted on rats showed that co-administration of GEM, PTX, and BAI in the _LBSNEP enhanced the respective relative oral bioavailability levels of GEM and PTX by 1.5- and 2-fold, respectively, compared to the solution group. The tumor inhibition study was conducted with metronomic therapy at a low daily dose compared to conventional therapy at a higher dose every 3 days. Results indicated that oral metronomic delivery of GEM/PTX/BAI _LBSNEP could inhibit tumor growth during administration phase, and that there were similar tumor volumes compared to traditional chemotherapy at day 28 even if the dose of metronomic chemotherapy was 2.2-fold less than that of the latter. In conclusion, a self-nanoemulsifying drug-delivery system for the oral delivery of GEM, PTX, and BAI in a metronomic manner enhanced the therapeutic effect on pancreatic cancer, providing an alternative option for chemotherapy.

Keywords: Baicalein; Gemcitabine; Lecithin-based self-nanoemulsifying preconcentrate ((LB)SNEP); Metronomic chemotherapy; Paclitaxel.