Biomedical Engineering Reference
In-Depth Information
Delivery to Intracellular Targets
by Nanosized Particles
Gillian Barratt
Abstract
Nanosized drug carrier systems, including liposomes and nanoparticles,
have the potential of delivering their contents to the interior of cells. However,
engineering of the particle size and surface properties is necessary to achieve target-
ing to particular cell types. Conventional particles with hydrophobic surfaces are
rapidly engulfed by phagocytic cells. Modification of the surface with hydrophilic
polymers yields so-called “Stealth” particles which avoid phagocytosis and remain
in the circulation longer after intravenous injection. The addition of specific ligands
to the surface of these particles can confer more specific targeting to particular cell
types. Nanoparticles and liposomes are normally taken up by endocytosis in non
phagocytic cells, leading to their delivery to the lysosomal compartment. In order
for the cargo to reach other cell compartments, a mechanism of endosomal escape
is necessary. Examples are given of drug delivery in two particular applications:
delivery to macrophages for immunomodulating and anti-infectious functions, and
delivery of antisense oligonucleotides and small interfering RNA to cells.
Keywords
Liposome
•
Nanoparticle
•
Endocytosis
•
Macrophage
•
Nucleic acids
Abbreviations
AS-ODN
antisense oligo deoxynucleotide
CHEMS
cholesteryl hemisuccinate
DC-Chol
3ß-[N-(N¢,N¢-dimethylaminoethane)-carbamoyl]cholesterol
DNA
deoxyribonucleic acid
DOGS
dioctadecylamidoglycylspermine
DOPE
dioleoylphosphatidylethanolamine
G. Barratt (
*
)
CNRS UMR 8612, Faculty of Pharmacy, Université Paris-Sud XI, 5 rue J.B. Clément,
Chatenay-Malabry F92296, France
e-mail: gillian.barratt@u-psud.fr
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