title: Laronidase-functionalized multiple-wall lipid-core nanocapsules: promising formulation for a more effective treatment of mucopolysaccharidosis type I.
abstract: OBJECTIVE
  Mucopolysaccharidosis I is a genetic disorder caused by alpha-L-iduronidase deficiency. Its primary treatment is enzyme replacement therapy (ERT), which has limitations such as a high cost and a need for repeated infusions over the patient's lifetime. Considering that nanotechnological approaches may enhance enzyme delivery to organs and can reduce the dosage thereby enhancing ERT efficiency and/or reducing its cost, we synthesized laronidase surface-functionalized lipid-core nanocapsules (L-MLNC).
  
  
  METHODS
  L-MLNCs were synthesized by using a metal complex. Size distributions were evaluated by laser diffraction and dynamic light scattering. The kinetic properties, cytotoxicity, cell uptake mechanisms, clearance profile and biodistribution were evaluated.
  
  
  RESULTS
  Size distributions showed a D[4,3] of 134 nm and a z-average diameter of 71 nm. L-MLNC enhanced the Vmax and Kcat in comparison with laronidase. L-MLNC is not cytotoxic, and nanocapsule uptake by active transport is not only mediated by mannose-6-phosphate receptors. The clearance profile is better for L-MLNC than for laronidase. A biodistribution analysis showed enhanced enzyme activity in different organs within 4 h and 24 h for L-MLNC.
  
  
  CONCLUSIONS
  The use of lipid-core nanocapsules as building blocks to synthesize surface-functionalized nanocapsules represents a new platform for producing decorated soft nanoparticles that are able to modify drug biodistribution.
authors.affiliation: Gene Therapy Center, Experimental Research Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.
authors.forename: Fabiana Quoos
authors.initials: FQ
authors.lastname: Mayer
authors.forename: Márcia Duarte
authors.initials: MD
authors.lastname: Adorne
authors.forename: Eduardo André
authors.initials: EA
authors.lastname: Bender
authors.forename: Talita Giacomet
authors.initials: TG
authors.lastname: de Carvalho
authors.forename: Anna Cláudia
authors.initials: AC
authors.lastname: Dilda
authors.forename: Ruy Carlos Ruver
authors.initials: RC
authors.lastname: Beck
authors.forename: Sílvia Stanisçuaski
authors.initials: SS
authors.lastname: Guterres
authors.forename: Roberto
authors.initials: R
authors.lastname: Giugliani
authors.forename: Ursula
authors.initials: U
authors.lastname: Matte
authors.forename: Adriana Raffin
authors.initials: AR
authors.lastname: Pohlmann
mesh_terms: D000818:Animals; D019540:Area Under Curve; D001692:Biological Transport; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical; D056947:Enzyme Replacement Therapy / Q000009:adverse effects; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007068:Iduronidase / Q000008:administration & dosage / Q000737:chemistry* / Q000235:genetics / Q000493:pharmacokinetics / Q000633:toxicity; D007275:Injections, Intravenous; D008055:Lipids / Q000737:chemistry*; D008657:Metabolic Clearance Rate; D018345:Mice, Knockout; D008059:Mucopolysaccharidosis I / Q000188:drug therapy* / Q000201:enzymology; D053769:Nanocapsules; D050997:Nanomedicine; D010316:Particle Size; D013678:Technology, Pharmaceutical / Q000379:methods; D014018:Tissue Distribution
chemical_list: D008055:Lipids; D053769:Nanocapsules; D007068:Iduronidase