PMID- 33800701
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210428
IS  - 1999-4923 (Print)
IS  - 1999-4923 (Electronic)
IS  - 1999-4923 (Linking)
VI  - 13
IP  - 4
DP  - 2021 Mar 28
TI  - Oligonucleotide Delivery across the Caco-2 Monolayer: The Design and Evaluation 
      of Self-Emulsifying Drug Delivery Systems (SEDDS).
LID - 10.3390/pharmaceutics13040459 [doi]
LID - 459
AB  - 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.
FAU - Kubackova, Jana
AU  - Kubackova J
AUID- ORCID: 0000-0003-2472-6183
AD  - Department of Pharmaceutical Technology, Faculty of Pharmacy in Hradec Kralove, 
      Charles University, Akademika Heyrovskeho 1203, 500 05 Hradec Kralove, Czech 
      Republic.
FAU - Holas, Ondrej
AU  - Holas O
AUID- ORCID: 0000-0002-8335-0123
AD  - Department of Pharmaceutical Technology, Faculty of Pharmacy in Hradec Kralove, 
      Charles University, Akademika Heyrovskeho 1203, 500 05 Hradec Kralove, Czech 
      Republic.
FAU - Zbytovska, Jarmila
AU  - Zbytovska J
AD  - Department of Pharmaceutical Technology, Faculty of Pharmacy in Hradec Kralove, 
      Charles University, Akademika Heyrovskeho 1203, 500 05 Hradec Kralove, Czech 
      Republic.
AD  - Faculty of Chemical Technology, University of Chemistry and Technology Prague, 
      Technicka 5, 166 28 Prague, Czech Republic.
FAU - Vranikova, Barbora
AU  - Vranikova B
AUID- ORCID: 0000-0002-9824-1923
AD  - Department of Pharmaceutical Technology, Faculty of Pharmacy in Hradec Kralove, 
      Charles University, Akademika Heyrovskeho 1203, 500 05 Hradec Kralove, Czech 
      Republic.
FAU - Zeng, Guanghong
AU  - Zeng G
AD  - DFM A/S (Danish National Metrology Institute), Kogle Alle 5, 2970 Horsholm, 
      Denmark.
FAU - Pavek, Petr
AU  - Pavek P
AUID- ORCID: 0000-0001-8769-4196
AD  - Department of Pharmacology, Faculty of Pharmacy in Hradec Kralove, Charles 
      University, Akademika Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic.
FAU - Mullertz, Anette
AU  - Mullertz A
AD  - Department of Pharmacy, Faculty of Health and Medical Sciences, University of 
      Copenhagen, 2100 Copenhagen, Denmark.
AD  - Bioneer: FARMA, Department of Pharmacy, Faculty of Health and Medical Sciences, 
      University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark.
LA  - eng
GR  - SVV 260 402/Ministerstvo Skolstvi, Mladeze a Telovychovy/
GR  - CZ.02.1.01/0.0/0.0/16_019/0000841/European Food Safety Authority/
GR  - FM/c/2029-1-011/Univerzita Karlova v Praze/
GR  - CA16205/European Cooperation in Science and Technology/
PT  - Journal Article
DEP - 20210328
PL  - Switzerland
TA  - Pharmaceutics
JT  - Pharmaceutics
JID - 101534003
PMC - PMC8066367
OTO - NOTNLM
OT  - Caco-2 monolayer
OT  - hydrophobic ion pairing
OT  - intestinal permeation enhancers
OT  - oligonucleotide
OT  - self-emulsifying drug delivery systems
COIS- The authors declare no conflict of interest.
EDAT- 2021/04/04 06:00
MHDA- 2021/04/04 06:01
PMCR- 2021/03/28
CRDT- 2021/04/03 01:06
PHST- 2021/02/15 00:00 [received]
PHST- 2021/03/23 00:00 [revised]
PHST- 2021/03/24 00:00 [accepted]
PHST- 2021/04/03 01:06 [entrez]
PHST- 2021/04/04 06:00 [pubmed]
PHST- 2021/04/04 06:01 [medline]
PHST- 2021/03/28 00:00 [pmc-release]
AID - pharmaceutics13040459 [pii]
AID - pharmaceutics-13-00459 [pii]
AID - 10.3390/pharmaceutics13040459 [doi]
PST - epublish
SO  - Pharmaceutics. 2021 Mar 28;13(4):459. doi: 10.3390/pharmaceutics13040459.