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Mechanism of enhanced oral absorption of morin by phospholipid complex based self-nanoemulsifying drug delivery system
- Source :
- Molecular pharmaceutics. 12(2)
- Publication Year :
- 2014
-
Abstract
- Phospholipid complex (PLC) based self-nanoemulsifying drug delivery system (PLC-SNEDDS) has been developed for efficient delivery of drugs with poor solubility and low permeability. In the present study, a BCS class IV drug and a P-glycoprotein (P-gp) substrate, morin, was selected as the model drug to elucidate the oral absorption mechanism of PLC-SNEDDS. PLC-SNEDDS was superior to PLC in protecting morin from degradation by intestinal enzymes in vitro. In situ perfusion study showed increased intestinal permeability by PLC was duodenum-specific. In contrast, PLC-SNEDDS increased morin permeability in all intestinal segments and induced a change in the main absorption site of morin from colon to ileum. Moreover, ileum conducted the lymphatic transport of PLC-SNEDDS, which was proven by microscopic intestinal visualization of Nile red labeled PLC-SNEDDS and lymph fluids in vivo. Low cytotoxicity and increased Caco-2 cell uptake suggested a safe and efficient delivery of PLC-SNEDDS. The increased membrane fluidity and disrupted actin filaments were closely associated with the increased cell uptake of PLC-SNEDDS. PLC-SNEDDS could be internalized into enterocytes as an intact form in a cholesterol-dependent manner via clathrin-mediated endocytosis and macropinocytosis. The enhanced oral absorption of morin was attributed to the P-gp inhibition by Cremophor RH and the intact internalization of M-PLC-SNEDDS into Caco-2 cells bypassing P-gp recognition. Our findings thus provide new insights into the development of novel nanoemulsions for poorly absorbed drugs.
- Subjects :
- Cell Survival
Pharmaceutical Science
Morin
Pharmacology
Endocytosis
Intestinal absorption
chemistry.chemical_compound
Drug Delivery Systems
In vivo
Drug Discovery
Membrane fluidity
medicine
Animals
Humans
Rats, Wistar
Phospholipids
Flavonoids
Drug Carriers
Intestinal permeability
Models, Theoretical
medicine.disease
Rats
chemistry
Intestinal Absorption
Caco-2
Drug delivery
Molecular Medicine
Emulsions
Caco-2 Cells
Subjects
Details
- ISSN :
- 15438392
- Volume :
- 12
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Molecular pharmaceutics
- Accession number :
- edsair.doi.dedup.....747f8e0517a316a5b1dc9f42f483c5ef