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Monday, January 13, 2014 12:33:32 PM
Nanoparticles are solid colloidal matrix-like particles made of polymers1 or lipids.2 Generally administered by the intravenous route like liposomes, they have been developed for the targeted delivery of therapeutic or imaging agents. Their main advantages over liposomes are the low number of excipients used in their formulations, the simple procedures for preparation, a high physical stability, and the possibility of sustained drug release that may be suitable in the treatment of chronic diseases. Until the mid 1990s, their development as drug carriers was seriously limited by the lack of long-circulating properties.
3 Therefore, in contrast to liposomes and despite the abundance of experimental works and achievements in the field of nanoparticle technology, no nanoparticle-based drug formulation has been marketed so far. Due to their size ranging from 10 to 1000 nm (generally 50–300 nm), and like liposomes, they are unable to diffuse through the blood-brain barrier (BBB) to reach the brain parenchyma. Based on general parenteral formulation considerations and specific BBB features, Table Table 1 summarizes the ideal nanoparticle properties required for drug brain delivery.
4 One particularly interesting application of nanoparticule could be the drug brain delivery, accompanied with the local sustained release, of the new large molecule therapeutics now available to treat the CNS: peptides, proteins, genes, antisense drugs. Due to their poor stability in biological fluids, rapid enzymatic degradation, unfavorable pharmacokinetic properties, and lack of diffusion toward the CNS, they may be advantageously formulated in brain-targeted protective nanocontainers.
5 Compared with conventional drugs, they possess a high intrinsic pharmacological activity. The small dose requested for therapeutic efficiency could easily fit the loading capacity of nanoparticles and would not require the administration of large amount of potentially toxic nanoparticle excipient. Because of the large variety of the nanoparticles developed so far, this review will focus on nanoparticles investigated for brain delivery. Nanoparticles made of polybutylcyanoacrylate (PBCA, FIG. 1) have been intensely investigated since the first papers in 1995 showing that when coated with the nonionic surfactant polysorbate 80 they permitted to deliver drugs to the brain.
6,7 Despite interesting results, PBCA nanoparticles have limitations, discussed in this review, that may preclude, or at least limit, their potential clinical applications. Nanoparticles made of polylactide homopolymers (PLA) or poly(lactide-co-glycolide) heteropolymers (PLGA) may be a promising alternative. In the mid 1990s, long-circulating pegylated PLA or PLGA nanoparticles have been made available that opened great opportunities for drug targeting.3 Pegylated nanoparticles are made of methoxypoly(ethylene glycol)-PLA/PLGA (mPEG-PLA/PLGA, FIG. 1), i.e., esters of PLA or PLGA with PEG of various molecular weights. More recently, the synthesis of functionalized pegylated PLA/PLGA nanoparticles opened new perspectives for targeted drug delivery in general, and for drug brain targeting in particular. This review will present their general properties and will propose preparation methods of brain-targeted pegylated nanoparticles...
TABLE 1.
Ideal Properties of Nanoparticles for Drug Brain Delivery
-Nontoxic, biodegradable, and biocompatible
-Particle diameter < 100 nm
-Physical stability in blood (no aggregation)
-Avoidance of the MPS (no opsonization), prolonged blood circulation time
-BBB-targeted and brain delivery (receptor-mediated transcytosis across brain capillary endothelial cells)
-Scalable and cost-effective manufacturing process
-Amenable to small molecules, peptides, proteins, or nucleic acids
-Minimal nanoparticle excipient-induced drug alteration (chemical degradation/alteration, protein denaturation)
-Possible modulation of drug release profiles
source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC539329/
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