Development of nanoparticle-bound arylsulfatase B for enzyme replacement therapy of mucopolysaccharidosis VI.
Lysosomal storage disorders like mucopolysaccharidosis (MPS) VI are rare diseases with a lack of well-suited treatments. Even though an enzyme replacement therapy (ERT) of recombinant arylsulfatase B (ASB) is available for MPS VI, the administration cannot positively affect the neurologic manifestations such as spinal cord compression. Since nanoparticles (NP) have shown to be effective drug carriers, the feasibility of arylsulfatase B adsorption onto poly(butyl cyanoacrylate) (PBCA) nanoparticles was investigated in this study. In order to advance the ERT of ASB, the adsorption of the latter on the surface of PBCA NP as well as in vitro release in serum was investigated. With alteration of parameters like temperature, incubation time, pH, and enzyme amount, the adsorption process revealed to be stable with a maximum capacity of 67 microg/mg NP at a pH of 6.3. In vitro release experiments demonstrated that the adsorption is stable for at least 60 minutes in human blood serum, indicating that the ASB-loaded PBCA nanoparticles represent a promising candidate for ERT of MPS VI.
Institute of Pharmaceutical Technology, Johann Wolfgang Goethe University, Frankfurt am Main, Germany.
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A
Mühlstein
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S
Gelperina
J
J
Kreuter
D000327:Adsorption; D000465:Algorithms; D001812:Blood-Brain Barrier / Q000378:metabolism; D002849:Chromatography, Gas; D002850:Chromatography, Gel; D004339:Drug Compounding; D016503:Drug Delivery Systems; D056947:Enzyme Replacement Therapy; D005079:Excipients; D006801:Humans; D008855:Microscopy, Electron, Scanning; D009087:Mucopolysaccharidosis VI / Q000188:drug therapy* / Q000201:enzymology; D020051:N-Acetylgalactosamine-4-Sulfatase / Q000627:therapeutic use*; D053758:Nanoparticles; D010316:Particle Size; D013816:Thermodynamics
D005079:Excipients; D020051:N-Acetylgalactosamine-4-Sulfatase