Journal
COLLOIDS AND SURFACES B-BIOINTERFACES
Volume 197, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.colsurfb.2020.111369
Keywords
Cordycepin; Oral administration; Hybrid nanocarrier; Colon cancer
Funding
- Thailand Science Research and Innovation (TSRI) Early career researcher grant -Thailand Research Fund(TRF) [TRG5980008]
- Graduate Institute of Science and Technology Scholarship (TGIST) from National Science and Technology Development Agency (NSTDA, Thailand) [SCA-CO-2561-7042TH]
- 90th Anniversary of Chulalongkorn University Fund (Ratchadaphiseksomphot Endowment Fund) Batch 45, Chulalongkorn University (CU, Thailand) [1/2020]
- National Nanotechnology Center (NANOTEC)Thailand
- National Nanotechnology Platform grant (NPT) [P1851708]
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A hybrid nanocarrier system comprising biloniosome-core/chitosan-shell was developed to enhance the bioavailability of cordycepin. The system showed enhanced mucoadhesive characteristics, stability in gastric fluid, and increased permeability across the intestinal barrier. Cordycepin-loaded HNCs demonstrated effective anti-cancer activity in both 2D cell cultures and 3D multi-cellular spheroids of colon cancer cells. Quantitative real time PCR analysis revealed the mechanism by which cordycepin HNCs induce apoptosis in cancer cells. This study suggests that hybrid nanocarrier systems could be a promising strategy for improving the bio-characteristics of cordycepin as a potential anti-cancer agent for colorectal cancer chemotherapy.
Cordycepin, a derivative of the nucleotide adenosine, has displayed several pharmacological activities including enhanced apoptosis and cancer cells inhibition. However, oral administration of cordycepin has limited practical use due to its poor bioavailability in the intestine. Herein, we developed and demonstrated a hybrid nanocarrier system in the form of biloniosome-core/chitosan-shell hybrid nanocarriers (HNCs) in order to improve the biocharacteristics of cordycepin. In this study, HNCs were prepared by using a solvent (ethanol) injection method involving cordycepin as the biloniosome core and mucoadhesive chitosan biopolymer as a coating shell. Our results showed that the cordycepin-loaded HNCs were positively charged with enhanced mucoadhesive characteristics and highly stable in gastric fluid. The increased permeability of cordycepin-loaded HNCs compared with standard cordycepin was confirmed by in vitro intestinal permeation study across the human intestinal barrier. In addition, we demonstrated that the cordycepin-loaded HNCs are able to release their components in an active form resulting in enhanced anti-cancer activity in two-dimensional (2D) cell cultures as well as in three-dimensional (3D) multi-cellular spheroids of colon cancer cells. Further, quantitative real time PCR analysis of apoptotic gene expression revealed that cordycepin HNCs can induce apoptosis in cancer cells by negatively regulating the expression of B-cell lymphoma-extra large (BCL-XL). I Overall our results showed that the hybrid nanocarrier systems represent a promising strategy for improving the bio-characteristics of cordycepin which can be considered as a potential anti-cancer agent for colorectal cancer chemotherapy.
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