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

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.

Treatment of MPS I mice with microencapsulated cells overexpressing IDUA: effect of the prednisolone administration.

Cell encapsulation, although a promising strategy to deliver therapeutic products, is hampered by immune response against biomaterials. The aim of this article is to assess the effect of prednisolone on enzyme release by microencapsulated cells implanted in vivo. Recombinant cells encapsulated were implanted in the peritoneum of wild-type mice and mucopolysaccharidosis (MPS) I mice, with or without prednisolone. Later, microcapsules were recovered for histological and enzyme analysis. Blood was collected from MPS I mice. All animals receiving prednisolone had a smaller inflammatory infiltrate. In vitro, prednisolone increased the amount of enzyme released from the recovered capsules, but this was not accompanied by an increase in the amount of circulating enzyme in vivo after 15 days. However, in 7 days, prednisolone significantly increased the amount of enzyme detected in the serum. Although prednisolone improved enzyme release in vitro and in vivo after 7 days, it was unable to maintain this effect for a longer period.