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Formulation of Didanosine Prodrugs into PEGylated Poly(alkyl cyanoacrylate) Nanoparticles and Uptake by Brain Endothelial Cells

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Abstract:

PEGylated 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.

Keywords: BRAIN ENDOTHELIAL CELLS; DIDANOSINE; GLYCEROLIPIDIC PRODRUG; HIV; PEGYLATED NANOPARTICLES

Document Type: Research Article

DOI: http://dx.doi.org/10.1166/jns.2009.1007

Publication date: December 1, 2009

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  • Recent advances in nanomaterials indicates that the central nervous system (CNS) is susceptible to nanoparticle induced alterations leading to functional or structural alterations. This knowledge is currently disseminated in vast array of journals dealing with broad subject areas related to pharmacology, toxicology, neuroscience or nanosciences. Thus, there is an urgent need to collect all these diverse information related to nanoscience and brain function in one place using Journal of Nanoneuroscience for the benefit of the scientific community, researchers, health planners, health care providers, policy makers, environmentalists, biologists, chemists, and physicist in this emerging area of medical science.
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