Journal
INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 616, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.ijpharm.2022.121522
Keywords
Nanocrystals; Multicomponent; Bufadienolides; Transcytosis; Intestinal absorption
Categories
Funding
- National Natural Scien-ce Foundations of China [81860628]
- Ningxia key research and development projects [2019BEG03038, 2018BFH02001, 2017BY084]
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This study demonstrates the potential of using nanocrystals for oral delivery of multicomponent anticancer drugs. The nanocrystals improved drug dissolution behavior and permeation through the mucus layer, enhanced cellular uptake, and improved intestinal absorption efficiency.
Using nanocrystals (NCs) technology may be a promising drug delivery strategy for oral administration of multicomponent anticancer drugs. However, the intestinal epithelium and the mucus layer on the intestine extremely limited drug transport and absorption by orally. In this study, we selected multicomponent inartificial compound Bufadienolides (BU) with broad spectrum antitumor activity as the model drug to prepare BU NCs with different stabilizers by wet grinding, and explored the efficiency of penetrating through the mucus layer and transporting intestinal epithelial cells in vitro and ex vivo. Results revealed that BU NCs can dramatically improve dissolution behavior synergistically and the efficiency of mucus permeation. Besides, we found that BU NCs with different stabilizers enhanced cellular uptake, which was mainly attributed to increasing or changing the endocytosis pathway and plasma membrane/Endoplasmic reticulum (ER) pathway involved in the trans membrane transport of NCs. Furthermore, BU NCs could definitely improve intestinal absorption efficiency and change the absorption site of BU ex vivo. This multi-angle exploration will provide reference for the development of BU oral delivery formulations.
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