Laronidase-functionalized multiple-wall lipid-core nanocapsules: promising formulation for a more effective treatment of mucopolysaccharidosis type I.

Abstract

PURPOSE:

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: Fabiana Quoos Mayer, Márcia Duarte Adorne, Eduardo André Bender, Talita Giacomet de Carvalho, Anna Cláudia Dilda, Ruy Carlos Ruver Beck, Sílvia Stanisçuaski Guterres, Roberto Giugliani, Ursula Matte, Adriana Raffin Pohlmann
• Journal: Pharmaceutical research (Pharm Res) Vol. 32 Issue 3 Pg. 941-54 (Mar 2015) ISSN: 1573-904X [Electronic] United States
• PMID: 25208876 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Lipids
• Nanocapsules
• Iduronidase

Topics

• Animals
• Area Under Curve
• Biological Transport
• Cell Survival (drug effects)
• Cells, Cultured
• Chemistry, Pharmaceutical
• Enzyme Replacement Therapy (adverse effects)
• Fibroblasts (drug effects, metabolism, pathology)
• Iduronidase (administration & dosage, chemistry, genetics, pharmacokinetics, toxicity)
• Injections, Intravenous
• Lipids (chemistry)
• Metabolic Clearance Rate
• Mice, Knockout
• Mucopolysaccharidosis I (drug therapy, enzymology)
• Nanocapsules
• Nanomedicine
• Particle Size
• Technology, Pharmaceutical (methods)
• Tissue Distribution