Journal
PHARMACEUTICS
Volume 14, Issue 9, Pages -Publisher
MDPI
DOI: 10.3390/pharmaceutics14091913
Keywords
antitumor efficacies; berberine hydrochloride; small extracellular vesicles
Categories
Funding
- INSERM
- Universite of Montpellier
- Campus France
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This study utilized small extracellular vesicles (sEVs) to enhance the stability and efficacy of berberine hydrochloride (BRB). The results showed that sEVs loaded with BRB had greater inhibitory effects on proliferation, migration, and capillary-like formation in tumor cells and endothelial cells compared to free BRB. Therefore, sEV-loaded BRB may be considered as an innovative delivery method to prevent tumorigenesis and angiogenesis.
Berberine hydrochloride (BRB) is an isoquinoline alkaloid with promising anticancer efficacies. However, application of BRB had been hampered by its poor aqueous solubility, low gastrointestinal absorption, and rapid metabolism. The present study takes advantage of small extracellular vesicles (sEVs) to increase both stability and efficacy of BRB. sEVs from immature dendritic cells were produced and loaded with BRB. Proliferation, migration and Matrigel assay were performed, cycle arrest and nitric oxide (NO) production were evaluated in human breast cancer cell line (MDA-MB-231) and human umbilical vein endothelial cells (HUVECs). sEVs loaded with BRB formed a stable and homogenous population with a drug entrapment efficiency near to 42%. BRB loaded into sEVs was more potent than free BRB for MDA-MB-231 and endothelial proliferation, migration, and capillary-like formation in HUVECs. The mechanisms involved a blockade of cell cycle in G0/G1 phase, increased S phase and decreased of G2/M in MDA-MB-231 and HUVECs, and inhibition of NO production in HUVECs. Altogether, sEV-loaded BRB displayed higher effects than free BRB on different steps leading to its antitumor activity and anti-angiogenic properties in vitro. Thus, sEV formulation may be considered as an innovative approach and promising delivery of BRB to prevent tumorigenesis and angiogenesis.
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