Cholesterol transport from liposomal delivery vehicles

Azadeh Kheirolomoom, Katherine W. Ferrara

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Rapid internalization of drugs from delivery vehicles via non-endocytotic pathways is an important goal. The transport of imaging probes attached to cholesterol and introduced via a liposomal formulation is considered here, in order to evaluate the intracellular distribution and kinetics of small molecular cargo that might be attached to cholesterol or phospholipids. The internalization efficiencies of two fluorescent cholesterol analogues, one carrying a fluorophore on the head of the cholesterol molecule 4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-dodecanoate (BODIPY)-cholesteryl ester (CE) (BODIPY-CE) and the other on the tail (25-[N-[(7-nitro-2-1,3-benzoxadiazol-4-yl)-methyl]amino]-27-norcholesterol (NBD-cholesterol)), were compared with those of other phospholipid molecules (NBD-phosphatidylcholine (PC) and NBD-phosphatidylethanolamine (PE)) using a liposomal formulation (1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 85.5 m%; 1,2 distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG2k), 9.5 m%; fluorescent analogue, 5 m%). The rate and transfer efficiency were NBD-cholesterol>BODIPY-CE>NBD-PC>NBD-PE. NBD-cholesterol, delivered by liposomes with an average diameter of 100 nm, localized in the perinuclear region and lipid storage droplets, with transfer observed in as little as 5 min. NBD-cholesterol transport was approximately constant with time, suggesting a unidirectional mode of entry. In the absence of PEG within the liposome, the transfer rate decreased. Filipin, a caveolae-blocking agent, caused 70% inhibition of cholesterol internalization in treated cells, suggesting that cholesterol internalization follows a caveolae-mediated pathway.

Original languageEnglish (US)
Pages (from-to)4311-4320
Number of pages10
JournalBiomaterials
Volume28
Issue number29
DOIs
StatePublished - Oct 2007

Fingerprint

Cholesterol
Caveolae
Liposomes
Cholesterol Esters
Phospholipids
Polyethylene glycols
Esters
Filipin
Laurates
Molecules
Fluorophores
Lipids
Cells
Imaging techniques
Kinetics
Pharmaceutical Preparations

Keywords

  • Caveolae
  • Cholesterol internalization
  • Drug delivery
  • Endocytosis pathway
  • Liposome

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering

Cite this

Cholesterol transport from liposomal delivery vehicles. / Kheirolomoom, Azadeh; Ferrara, Katherine W.

In: Biomaterials, Vol. 28, No. 29, 10.2007, p. 4311-4320.

Research output: Contribution to journalArticle

Kheirolomoom, Azadeh ; Ferrara, Katherine W. / Cholesterol transport from liposomal delivery vehicles. In: Biomaterials. 2007 ; Vol. 28, No. 29. pp. 4311-4320.
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KW - Liposome

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