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  • Title: In vivo brain microdialysis to evaluate FITC-dextran encapsulated immunopegylated nanoparticles.
    Author: Bommana MM, Kirthivasan B, Squillante E.
    Journal: Drug Deliv; 2012 Aug; 19(6):298-306. PubMed ID: 22928708.
    Abstract:
    CONTEXT: Delivery of drugs and dyes through intact blood-brain barrier (BBB) is extremely sought-after. A safe and reliable measurement of delivery efficacy in live animals is necessary. OBJECTIVE: To investigate the brain uptake of FITC-dextran MW 4000 (FD4) by CD71/OX-26 coated nanoparticles by microdialysis sampling and fluorescence/confocal microscopy. MATERIALS AND METHODS: Methoxy-poly(ethylene glycol)-poly(lactide) (Met-PEG-PLA) and maleimide-poly(ethylene glycol)-poly(lactide) (Mal-PEG-PLA) nanoparticles were prepared by nanoprecipitation. The surfaces of the prepared nanoparticles were embellished with CD-71/OX-26 antibodies for brain targeting. Male Sprague Dawley rats received 0.4 mg/kg FD4 and equivalent nanoparticulate formulation through lateral tail vein. Animals were euthanized 24 h postadministration, after which the tissues were harvested and analyzed for FD4 concentrations. Tissues were fixed with paraformaldehyde, cryotomed to 20 µm sections, and analyzed by Total Internal Reflection microscopy. RESULTS: Particle sizes of 200 ± 25 nm and zeta potentials of -18 ± 1 mV were obtained. FD4 concentrations, determined using in vivo brain microdialysis, were high on the first day (~360 ng/mL) compared to 60 ng/mL on the following 2 days. The nanoparticle treated animals showed significantly higher (p < 0.05) FD4 concentrations in the brain than pure-FD4 treated animals. Immunopegylated nanoparticles sustained and enhanced Central nervous system (CNS) concentration of hydrophilic dye for at least 3 days. CONCLUSION: Immunopegylated nanoparticles produce enhanced and sustained uptake of brain permeability marker FD4 relative to controls.
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