Synergistic Combination of Irinotecan and Rapamycin Orally Delivered by Nanoemulsion for Enhancing Therapeutic Efficacy of Pancreatic Cancer

  • Pharmaceutics. 2023 Jan 31;15(2):473. doi: 10.3390/pharmaceutics15020473.
Yu-Hsuan Liu  1 ,  Ling-Chun Chen  2 ,  Wen-Ting Cheng  2 ,  Pu-Sheng Wei  1 ,  Chien-Ming Hsieh  1 ,  Ming-Thau Sheu  1 ,  Shyr-Yi Lin  3  4 ,  Hsiu-O Ho  1 ,  Hong-Liang Lin  5
Affiliations
  • 1. School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan.
  • 2. Department of Biotechnology and Pharmaceutical Technology, Yuanpei University of Medical Technology, Hsinchu 30015, Taiwan.
  • 3. Division of Gastroenterology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan.
  • 4. Department of General Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
  • 5. School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
PMID: 36839795 DOI: 10.3390/pharmaceutics15020473
Abstract

In recent years, combining different types of therapy has emerged as an advanced strategy for Cancer treatment. In these combination therapies, oral delivery of Anticancer drugs is more convenient and compliant. This study developed an irinotecan/rapamycin-loaded oral lecithin-based self-nanoemulsifying nanoemulsion preconcentrate (LBSNENPir/ra) and evaluated its synergistic combination effects on pancreatic Cancer. LBSNENP loaded with irinotecan and rapamycin at a ratio of 1:1 (LBSNENPir10/ra10) had a better drug release profile and smaller particle size (<200 nm) than the drug powder. Moreover, LBSNENPir10/ra10 exhibited a strong synergistic effect (combination index [CI] < 1.0) in cell viability and combination effect studies. In the tumor inhibition study, the antitumor activity of LBSNENPir10/ra10/sily20 against MIA PaCa-2 (a human pancreatic Cancer cell line) was significantly increased compared with the Other groups. When administered with rapamycin and silymarin, the area under the curve and the maximum concentration of irinotecan significantly improved compared with the control. We successfully developed an irinotecan/rapamycin-loaded oral self-nanoemulsifying nanoemulsion system to achieve treatment efficacy for pancreatic Cancer.

Keywords
combination therapy; irinotecan; oral nano pharmaceuticals; rapamycin; self-nanoemulsifying nanoemulsion; silymarin.
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