Oligonucleotide Delivery across the Caco-2 Monolayer: The
Design and Evaluation of Self-Emulsifying Drug Delivery Systems
(SEDDS)

J 2021

Oligonucleotide Delivery across the Caco-2 Monolayer: The Design and Evaluation of Self-Emulsifying Drug Delivery Systems (SEDDS)

KUBACKOVA, J., O. HOLAS, J. ZBYTOVSKA, B. VRANIKOVA, G.H. ZENG et. al.

Základní údaje

Originální název

Oligonucleotide Delivery across the Caco-2 Monolayer: The Design and Evaluation of Self-Emulsifying Drug Delivery Systems (SEDDS)

Autoři

KUBACKOVA, J., O. HOLAS, J. ZBYTOVSKA, B. VRANIKOVA, G.H. ZENG, P. PAVEK a A. MULLERTZ

Vydání

European Journal of Pharmaceutics and Biopharmaceutics, BASEL, Elsevier, 2021, 0939-6411

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30104 Pharmacology and pharmacy

Stát vydavatele

Švýcarsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 5.589

Kód RIV

RIV/00216224:14740/21:00124442

Organizační jednotka

Středoevropský technologický institut

DOI

http://dx.doi.org/10.3390/pharmaceutics13040459

UT WoS

000643506400001

Klíčová slova anglicky

oligonucleotide; self-emulsifying drug delivery systems; hydrophobic ion pairing; intestinal permeation enhancers; Caco-2 monolayer

Štítky

CF CRYO, ne MU, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 18. 5. 2022 13:55, Mgr. Pavla Foltynová, Ph.D.

Anotace

V originále

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.

Návaznosti

90127, velká výzkumná infrastruktura

Název: CIISB II

Citovat

KUBACKOVA, J., O. HOLAS, J. ZBYTOVSKA, B. VRANIKOVA, G.H. ZENG, P. PAVEK a A. MULLERTZ. Oligonucleotide Delivery across the Caco-2 Monolayer: The Design and Evaluation of Self-Emulsifying Drug Delivery Systems (SEDDS). European Journal of Pharmaceutics and Biopharmaceutics. BASEL: Elsevier, 2021, roč. 13, č. 4, s. 459-485. ISSN 0939-6411. Dostupné z: https://dx.doi.org/10.3390/pharmaceutics13040459.

@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 a 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, roč.~13, č.~4, s.~459-485. ISSN~0939-6411. Dostupné z: https://dx.doi.org/10.3390/pharmaceutics13040459.

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