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@article{1842612,
author = {Kubackova, J. and Holas, O. and Zbytovska, J. and Vranikova, B. and Zeng, G.H. and Pavek, P. and Mullertz, A.},
article_location = {BASEL},
article_number = {4},
doi = {http://dx.doi.org/10.3390/pharmaceutics13040459},
keywords = {oligonucleotide; self-emulsifying drug delivery systems; hydrophobic ion pairing; intestinal permeation enhancers; Caco-2 monolayer},
language = {eng},
issn = {0939-6411},
journal = {European Journal of Pharmaceutics and Biopharmaceutics},
title = {Oligonucleotide Delivery across the Caco-2 Monolayer: The Design and Evaluation of Self-Emulsifying Drug Delivery Systems (SEDDS)},
url = {https://www.mdpi.com/1999-4923/13/4/459},
volume = {13},
year = {2021}
}
TY - JOUR
ID - 1842612
AU - Kubackova, J. - Holas, O. - Zbytovska, J. - Vranikova, B. - Zeng, G.H. - Pavek, P. - Mullertz, A.
PY - 2021
TI - Oligonucleotide Delivery across the Caco-2 Monolayer: The Design and Evaluation of Self-Emulsifying Drug Delivery Systems (SEDDS)
JF - European Journal of Pharmaceutics and Biopharmaceutics
VL - 13
IS - 4
SP - 459
EP - 459
PB - Elsevier
SN - 09396411
KW - oligonucleotide
KW - self-emulsifying drug delivery systems
KW - hydrophobic ion pairing
KW - intestinal permeation enhancers
KW - Caco-2 monolayer
UR - https://www.mdpi.com/1999-4923/13/4/459
N2 - Oligonucleotides (OND) represent a promising therapeutic approach. However, their instability and low intestinal permeability hamper oral bioavailability. Well-established for oral delivery, self-emulsifying drug delivery systems (SEDDS) can overcome the weakness of other delivery systems such as long-term instability of nanoparticles or complicated formulation processes. Therefore, the present study aims to prepare SEDDS for delivery of a nonspecific fluorescently labeled OND across the intestinal Caco-2 monolayer. The hydrophobic ion pairing of an OND and a cationic lipid served as an effective hydrophobization method using either dimethyldioctadecylammonium bromide (DDAB) or 1,2-dioleoyl-3-trimethylammonium propane (DOTAP). This strategy allowed a successful loading of OND-cationic lipid complexes into both negatively charged and neutral SEDDS. Subjecting both complex-loaded SEDDS to a nuclease, the negatively charged SEDDS protected about 16% of the complexed OND in contrast to 58% protected by its neutral counterpart. Furthermore, both SEDDS containing permeation-enhancing excipients facilitated delivery of OND across the intestinal Caco-2 cell monolayer. The negatively charged SEDDS showed a more stable permeability profile over 120 min, with a permeability of about 2 x 10(-7) cm/s, unlike neutral SEDDS, which displayed an increasing permeability reaching up to 7 x 10(-7) cm/s. In conclusion, these novel SEDDS-based formulations provide a promising tool for OND protection and delivery across the Caco-2 cell monolayer.
ER -
KUBACKOVA, J., O. HOLAS, J. ZBYTOVSKA, B. VRANIKOVA, G.H. ZENG, P. PAVEK and A. MULLERTZ. Oligonucleotide Delivery across the Caco-2 Monolayer: The Design and Evaluation of Self-Emulsifying Drug Delivery Systems (SEDDS). \textit{European Journal of Pharmaceutics and Biopharmaceutics}. BASEL: Elsevier, 2021, vol.~13, No~4, p.~459-485. ISSN~0939-6411. Available from: https://dx.doi.org/10.3390/pharmaceutics13040459.
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