Other formats:
BibTeX
LaTeX
RIS
@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.
|