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  • Title: Comparative evaluation of the degree of pegylation of poly(lactic-co-glycolic acid) nanoparticles in enhancing central nervous system delivery of loperamide.
    Author: Kirby BP, Pabari R, Chen CN, Al Baharna M, Walsh J, Ramtoola Z.
    Journal: J Pharm Pharmacol; 2013 Oct; 65(10):1473-81. PubMed ID: 24028614.
    Abstract:
    OBJECTIVES: In this study, we examined the relative cellular uptake of nanoparticles (NPs) formulated using poly(lactic-co-glycolic acid) (PLGA) polymers with increasing degree of pegylation (PLGA-PEG) and their potential to deliver loperamide to the brain of a mouse. METHOD: NPs containing coumarin-6 or loperamide HCl were formulated using PLGA and PLGA-PEG, with PEG content of 5-15%, by the solvent evaporation method. NPs were characterised for size, surface charge, morphology, encapsulation efficiency and drug release. Cellular uptake of coumarin-6 NPs was examined in Caco-2 monolayers using confocal microscopy and central nervous system (CNS) delivery of loperamide HCl from the NPs was examined following intranasal administration in a mouse model. KEY FINDINGS: No difference in NP characteristics was observed, irrespective of degree of pegylation, except for the surface charge which increased with increasing PEG content. PLGA-PEG NPs were found to have increased cellular uptake in comparison to PLGA NPs. Interestingly, this pattern was reflected in the CNS delivery of loperamide HCl in the mouse model. CONCLUSION: The results from this study show that PLGA-PEG NPs have the potential to act as carriers for the noninvasive administration of therapeutic agents to the brain and possibly across other physiological barriers.
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