Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2009-11-9
pubmed:abstractText
The use of lipid nanocapsules (LNCs) has enabled an improvement of the oral bioavailability of paclitaxel (Ptx). However, mechanisms that support this recent observation are not yet understood. By focusing on the well defined in vitro Caco-2 model, the purpose of this study was to evaluate the transport of LNCs across a model intestinal barrier. Firstly, four sizes of paclitaxel or dye (Nile Red)-loaded LNCs were formulated and LNCs with sizes between 26.3+/-2.7 nm and 132.7+/-5.5 nm were obtained. Different transport and uptake experiments were then performed across a Caco-2 cells culture model using these LNCs. Paclitaxel-loaded LNCs improved permeability of Ptx across intestinal epithelium compared with free Ptx or Taxol by a factor of 3.5. At 37 degrees C particle size did not influence transport efficiency. However, at 4 degrees C a decrease in Ptx transport was observed with increasing size of LNCs. Thus, with LNCs of 25 nm size, the apparent permeability coefficient (P(app)) was 5.3+/-1.1 cm s(-1) at 37 degrees C and 2.2+/-0.4 cm s(-1) at 4 degrees C. In comparison in LNCs of 130 nm size, the P(app) decreased from 5.8+/-0.8 cm s(-1) at 37 degrees C to 0.5+/-0.1 cm s(-1) at 4 degrees C. The uptake of LNCs by Caco-2 cells and the incapacity of LNCs to open tight junctions were also demonstrated. Furthermore, experiment transports were performed in the presence of different inhibitors of endocytosis. Findings indicated a reduction of Ptx transport of 30+/-6% when cell cholesterol was depleted, 65+/-12% when caveolae-mediated endocytosis was inhibited and 20+/-8% when clathrin-mediated endocytosis was inhibited. Finally, transmission electronic microscopy showed the presence of nano-objects on the basolateral side of the Caco-2 cell monolayers when LNCs were applied on the apical side.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1873-4995
pubmed:author
pubmed:issnType
Electronic
pubmed:day
3
pubmed:volume
140
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
174-81
pubmed:meshHeading
pubmed-meshheading:19699246-Antineoplastic Agents, Phytogenic, pubmed-meshheading:19699246-Caco-2 Cells, pubmed-meshheading:19699246-Caveolae, pubmed-meshheading:19699246-Cell Membrane Permeability, pubmed-meshheading:19699246-Chemistry, Pharmaceutical, pubmed-meshheading:19699246-Cholesterol, pubmed-meshheading:19699246-Clathrin-Coated Vesicles, pubmed-meshheading:19699246-Drug Carriers, pubmed-meshheading:19699246-Drug Compounding, pubmed-meshheading:19699246-Endocytosis, pubmed-meshheading:19699246-Humans, pubmed-meshheading:19699246-Intestinal Absorption, pubmed-meshheading:19699246-Intestinal Mucosa, pubmed-meshheading:19699246-Kinetics, pubmed-meshheading:19699246-Lipids, pubmed-meshheading:19699246-Nanocapsules, pubmed-meshheading:19699246-Paclitaxel, pubmed-meshheading:19699246-Particle Size, pubmed-meshheading:19699246-Temperature, pubmed-meshheading:19699246-Tight Junctions
pubmed:year
2009
pubmed:articleTitle
Lipid nanocarriers improve paclitaxel transport throughout human intestinal epithelial cells by using vesicle-mediated transcytosis.
pubmed:affiliation
Ethypharm, 92213-Saint-Cloud Cedex, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't