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Efficient Oral Delivery of Poorly Water-Soluble Drugs Using Carnitine/Organic Cation Transporter 2-Mediated Polymeric Micelles
- Source :
- ACS Biomaterials Science & Engineering. 6:2146-2158
- Publication Year :
- 2020
- Publisher :
- American Chemical Society (ACS), 2020.
-
Abstract
- The intestine epithelium is considered to be the most critical obstacle for nanoparticles for oral delivery of water-insoluble and poorly absorbed drugs. Based on the specific transporters located on the apical membrane of the intestinal epithelium, the carnitine-conjugated polymeric micelles targeting to the carnitine/organic cation transporter 2 (OCTN2) were developed by combining carnitine-conjugated poly(2-ethyl-2-oxazoline)-poly(d,l-lactide) with monomethoxy poly(ethylene-glycol)-poly(d,l-lactide). The carnitine-conjugated micelles with favorable stability in gastrointestinal fluid were validated to remarkably increase the cellular internalization and transcellular transport, while these were not the cases in the presence of free carnitine. These were further confirmed by more distribution of the micelles within epithelial cells, on the apical and basolateral side of the epithelium in mice. Additionally, identification of the carnitine-conjugated micelles by OCTN2 was detected to facilitate cellular uptake of the micelles via fluorescence immunoassay. Both clathrin and caveolae/lipid rafts pathways mediated endocytosis and transcellular transport of the carnitine-conjugated micelles, implying the enrichment of endocytic and transcellular transport pathway compared with that of carnitine-unconjugated micelles. Further, the intracellular trafficking process of the carnitine-conjugated micelles was tracked under confocal laser scanning microscopy, which involved in intracellular compartments such as late endosomes, lysosomes, endoplasmic reticulum, and Golgi apparatus as well. In conclusion, the current study provided an efficient strategy to facilitate the oral absorption of water-insoluble and poorly absorbed agents using intestinal transporter-mediated polymeric micelles.
- Subjects :
- Polymers
Endosome
0206 medical engineering
Biomedical Engineering
02 engineering and technology
Endocytosis
Clathrin
Micelle
Biomaterials
Mice
symbols.namesake
Carnitine
Animals
Lipid raft
Micelles
biology
Chemistry
Organic Cation Transporter 2
Water
Golgi apparatus
Apical membrane
021001 nanoscience & nanotechnology
020601 biomedical engineering
Paracellular transport
symbols
Biophysics
biology.protein
0210 nano-technology
Subjects
Details
- ISSN :
- 23739878
- Volume :
- 6
- Database :
- OpenAIRE
- Journal :
- ACS Biomaterials Science & Engineering
- Accession number :
- edsair.doi.dedup.....98d761e31247ab058f036736146ffdf5