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Delivery to Intracellular Targets by Nanosized Particles

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Intracellular Delivery

Part of the book series: Fundamental Biomedical Technologies ((FBMT,volume 5))

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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 targeting 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.

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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

DOTAP:

1,2-dioleoyl-3-trimethylammonium-propane

DOTMA:

1,2-di-O-octadecenyl-3-trimethylammonium propane

EPR:

enhanced permeation and retention

GAPDH:

glyceraldehyde 3-phosphate dehydrogenase

GFP:

green fluorescent protein

GPI:

glycosylphosphatidylinositol

HUVEC:

human umbilical vein endothelial cells

IgG:

immunoglobulin G

LDL:

low density lipoprotein

LHRH:

luteinizing-hormone-releasing hormone

MDP:

muramyl dipeptide

MTP-Chol:

muramyl tripeptide cholesterol

MTP-PE:

muramyl tripeptide phosphatidylethanolamine

NC:

nanocapsules

PACA:

poly (alkylcyanoacrylate)

PAMAM:

poly (amido amine)

PEG:

poly (ethylene glycol)

PEG-PMMA:

poly (ethylene glycol) – poly (methyl methacrylate) copolymer

PEI:

poly (ethyleneimine)

PIBCA:

poly (isobutylcyanoacrylate)

PIHCA:

poly (isohexylcyanoacrylate)

PLA:

poly (D, L-lactide)

PLGA:

poly (lactide –co-glycolide)

RGD:

Arg-Gly-Asp tripeptide

SAINT-2:

N-methyl-4(dioleyl)methylpyridinium chloride

SiRNA:

small interfering ribonucleic acid

VEGF-R2:

vascular endothelial growth factor receptor 2

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Barratt, G. (2011). Delivery to Intracellular Targets by Nanosized Particles. In: Prokop, A. (eds) Intracellular Delivery. Fundamental Biomedical Technologies, vol 5. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-1248-5_3

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