title: Development and characterization of PLGA nanoparticles as delivery systems of a prodrug of zidovudine obtained by its conjugation with ursodeoxycholic acid.
abstract: BACKGROUND
  Zidovudine (AZT) is employed against AIDS and hepatitis; its use is limited by active efflux transporters (AETs) that induce multidrug resistance for intracellular therapies and hamper AZT to reach the brain. Ursodeoxycholic acid (UDCA) conjugation with AZT (prodrug UDCA-AZT) allows to elude the AET systems.
  
  
  OBJECTIVE
  To investigate the effect of the Pluronic F68 coating on the loading, release and stability of poly(D,L lactide-co-glicolide) nanoparticles (NPs) embedded with UDCA-AZT.
  
  
  METHODS
  The mean diameter of the NP prepared by nanoprecipitation or emulsion/solvent evaporation methods was determined using both photon correlation spectroscopy and sedimentation field-flow fractionation; particle morphology was detected by scanning electron microscope. The stability of the free and encapsulated UDCA-AZT was evaluated in rat liver homogenates by high-performance liquid chromatography analysis.
  
  
  CONCLUSIONS
  The mean diameter of the NPs was found to be ∼ 600 nm with a relatively high polydispersity. The NPs obtained by emulsion/solvent evaporation were not able to control the prodrug release, differently from NPs obtained by nanoprecipitation. The presence of the Pluronic coating did not substantially modify the kinetics of the drug release, or the extent of the burst effect that were instead only influenced by the preparation parameters. UDCA-AZT incorporated in the NPs was more stable in the rat liver homogenates than the free prodrug and no influence of the Pluronic coating was observed.
  
  
  CONCLUSIONS
  Considering the different potential applications of nanoparticles coated and uncoated with Pluronic (brain and macrophage targeting, respectively), both of these nanoparticle systems could be useful in the therapies against HIV.
authors.affiliation: Department of Chemical and Pharmaceutical Sciences .
authors.forename: Alessandro
authors.initials: A
authors.lastname: Dalpiaz
authors.forename: Catia
authors.initials: C
authors.lastname: Contado
authors.forename: Lara
authors.initials: L
authors.lastname: Mari
authors.forename: Daniela
authors.initials: D
authors.lastname: Perrone
authors.forename: Barbara
authors.initials: B
authors.lastname: Pavan
authors.forename: Guglielmo
authors.initials: G
authors.lastname: Paganetto
authors.forename: Miriam
authors.initials: M
authors.lastname: Hanuskovà
authors.forename: Eleonora
authors.initials: E
authors.lastname: Vighi
authors.forename: Eliana
authors.initials: E
authors.lastname: Leo
mesh_terms: D000818:Animals; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers; D004355:Drug Stability; D006868:Hydrolysis; D007700:Kinetics; D019344:Lactic Acid / Q000737:chemistry*; D008099:Liver / Q000378:metabolism; D008297:Male; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles; D036103:Nanotechnology; D010316:Particle Size; D020442:Poloxamer / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011355:Prodrugs / Q000737:chemistry*; D017208:Rats, Wistar; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry* / Q000378:metabolism; D012995:Solubility; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods; D014580:Ursodeoxycholic Acid / Q000031:analogs & derivatives / Q000737:chemistry* / Q000378:metabolism; D015215:Zidovudine / Q000031:analogs & derivatives / Q000737:chemistry* / Q000378:metabolism
chemical_list: D004337:Drug Carriers; D011355:Prodrugs; D018894:Reverse Transcriptase Inhibitors; D020442:Poloxamer; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D015215:Zidovudine; D014580:Ursodeoxycholic Acid