Formulation of didanosine prodrugs into PEGylated poly(alkyl cyanoacrylate) nanoparticles and uptake by brain endothelial cells

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DOIResolve DOI: http://doi.org/10.1166/jns.2009.1007
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TypeArticle
Journal titleJournal of Nanoneuroscience
ISSN1939-0637
Volume1
Issue2
Pages174183; # of pages: 10
Subjectbrain endothelial cells; didanosine; glycerolipidic prodrug; hiv; PEGylated nanoparticles
AbstractPEGylated biodegradable nanoparticles based on poly(alkyl cyanoacrylate) polymers have been investigated to encapsulate didanosine prodrugs as an approach to treat HIV-1 associated dementia. To achieve this goal, an amphiphilic poly[(poly(ethylene glycol) cyanoacrylate)-co-(hexadecyl cyanoacrylate)] (PEGCA-PHDCA) copolymer has been synthesized and two different didanosine prodrugs have been used; the dipalmitoyl glycerol didanosine (ProddINP) and the dipalmitoyl glycerol phosphate didanosine (ProddIP), only differ by the presence or not of a phosphate group in their chemical structure. By means of differential scanning calorimetry (DSC), the capacity of PEGCA-PHDCA copolymer to incorporate ProddINP and ProddIP prodrugs was investigated. PEGCA-PHDCA nanoparticles were then prepared via an optimised solvent emulsion/evaporation technique using the incorporation ratios determined by DSC. Finally, confocal laser scanning microscopy experiments have shown these prodrugs-loaded nanoparticles were uptaken by rat immortalised brain endothelial cells (SV-ARBEC). These first results appeared promising for further in vitro and in vivo evaluation of these nanoparticles.
Publication date
LanguageEnglish
AffiliationNational Research Council Canada
Peer reviewedYes
NPARC number21275165
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Record identifier30327620-6fc6-4b8e-8ef5-50dba99bb491
Record created2015-05-21
Record modified2016-05-09
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