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WIREs Nanomed Nanobiotechnol
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Polyalkylcyanoacrylate nanoparticles for delivery of drugs across the blood–brain barrier

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The major problem in drug delivery to the brain is the presence of the blood–brain barrier (BBB) which limits drug penetration even if in certain pathological situations the BBB is partly disrupted. Among noninvasive techniques to overcome this barrier, the use of nanoparticles has been proposed. This review focuses on poly(alkylcyanoacrylates) (PACA)‐based nanoparticles which have been developed for brain targeting. Both types of ‘stealth’ PACA nanoparticles with modified surface, those coated with surfactant and those with chains of polyethylene glycol (PEG) linked to the hydrophobic core of PACA are presented. The synthesis of polymers, the preparation of nanoparticles with modified surface and their physicochemical characterization are described. The review of their in vivo results evidenced their ability to enter into the brain using healthy animals or models of central nervous system (CNS) diseases. The nature of the surface modification (surfactant nature, PEG linkage, drug loading interference) seems to have a great influence on the efficacy of brain targeting which can be related to the adsorption of some apolipoproteins (Apo E, B, A‐I). The mechanism of their passage through the BBB has been studied by in vitro and in vivo experiments, which suggested the implication of receptor‐mediated endocytosis processes. According to these data, some antibodies (OX26) and ligands (transferrin, Apo E/B/A‐I) seem to be good candidates to be coupled with ‘stealth’ PACA nanoparticles in order to increase their passage through the BBB and to promote active targeting to the brain Copyright © 2009 John Wiley & Sons, Inc.

Figure 1.

Structures of (a) Poly(butylcyanoacrylate) (PBCA), (b) PHDCA polymers, and (c) PEG‐PHDCA copolymer.

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Figure 2.

Scheme of the degradation process of poly(alkylcyanoacrylates) (PACA) polymers by esterases.

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Figure 3.

Schematic representation of stealth poly(alkylcyanoacrylates) (PACA) nanoparticles developed for brain targeting: (a) PS80 coated‐Poly(butylcyanoacrylate) (PBCA) nanoparticles, (b) PEG‐PHDCA nanoparticles.

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Figure 4.

Potential mechanism scheme of the endothelial cell uptake after IV injection of stealth poly(alkylcyanoacrylates) (PACA) nanoparticles.

[ Normal View | Magnified View ]

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In the Spotlight

James F. Leary

James F. Leary
has been contributing to nanomedical research and technologies throughout his career. Such contributions include the invention of high-speed flow cytometry, cell sorting techniques, and rare-event methods. Dr. Leary’s current research spans across three general areas in nanomedicine. The first is the development of high-throughput single-cell flow cytometry and cell sorting technologies. The second explores BioMEMS technologies. These include miniaturized cell sorters, portable devices for detection of microbial pathogens in food and water, and artificial human “organ-on-a-chip” technologies which consists of developing cell culture chips capable of simulating the activities and mechanics of entire organs and organ systems. His third area of research aims at developing smart nano-engineered systems for single-cell drug or gene delivery for nanomedicine. Dr. Leary currently holds nine issued U.S. Patents with four currently pending, and he has received NIH funding for over 25 years.

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