Drug transport to brain with targeted nanoparticles.
Nanoparticle drug carriers consist of solid biodegradable particles in size ranging from 10 to 1000 nm (50-300 nm generally). They cannot freely diffuse through the blood-brain barrier (BBB) and require receptor-mediated transport through brain capillary endothelium to deliver their content into the brain parenchyma. Polysorbate 80-coated polybutylcyanoacrylate nanoparticles can deliver drugs to the brain by a still debated mechanism. Despite interesting results these nanoparticles have limitations, discussed in this review, that may preclude, or at least limit, their potential clinical applications. Long-circulating nanoparticles made of methoxypoly(ethylene glycol)- polylactide or poly(lactide-co-glycolide) (mPEG-PLA/PLGA) have a good safety profiles and provide drug-sustained release. The availability of functionalized PEG-PLA permits to prepare target-specific nanoparticles by conjugation of cell surface ligand. Using peptidomimetic antibodies to BBB transcytosis receptor, brain-targeted pegylated immunonanoparticles can now be synthesized that should make possible the delivery of entrapped actives into the brain parenchyma without inducing BBB permeability alteration. This review presents their general properties (structure, loading capacity, pharmacokinetics) and currently available methods for immunonanoparticle preparation.
Olivier
Jean-Christophe
JC
Faculty of Medicine and Pharmacy, University of Poitiers, 86000 Poitiers, France. Jean.Christophe.Olivier@univ-poitiers.fr
D000818:Animals; D001921:Brain / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods*; D005079:Excipients; D006801:Humans; D008863:Microspheres; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010599:Pharmacokinetics; D011092:Polyethylene Glycols / Q000737:chemistry
D005079:Excipients; D004364:Pharmaceutical Preparations; D011092:Polyethylene Glycols
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