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.

Basic information

Original name

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

Authors

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

Edition

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

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30104 Pharmacology and pharmacy

Country of publisher

Switzerland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 5.589

RIV identification code

RIV/00216224:14740/21:00124442

Organization unit

Central European Institute of Technology

DOI

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

UT WoS

000643506400001

Keywords in English

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

Abstract

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.

Links

90127, large research infrastructures

Name: CIISB II

Citovat

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). 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.

@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.

Detailed Information on Publication Record