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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 &
Structures of (a) Poly(butylcyanoacrylate) (PBCA), (b) PHDCA polymers, and (c) PEG‐PHDCA copolymer.
Scheme of the degradation process of poly(alkylcyanoacrylates) (PACA) polymers by esterases.
Schematic representation of stealth poly(alkylcyanoacrylates) (PACA) nanoparticles developed for brain targeting: (a) PS80 coated‐Poly(butylcyanoacrylate) (PBCA) nanoparticles, (b) PEG‐PHDCA nanoparticles.
Potential mechanism scheme of the endothelial cell uptake after IV injection of stealth poly(alkylcyanoacrylates) (PACA) nanoparticles.
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