Proteins conjugated to poly(butyl cyanoacrylate) nanoparticles as potential neuroprotective agents.

Poly(butyl cyanoacrylate) (PBCA) nanoparticles (NPs) can penetrate blood-brain barrier providing the means for drug delivery to the central nervous system. Here, we study attachment of superoxide dismutase (SOD) and anti-glutamate N-methyl D-aspartate receptor 1 (NR1) antibody to PBCA NPs with the ultimate goal to design neuroprotective therapeutics for treatment of secondary spinal cord injury. Synthesis of monodispersed, ∼200 nm-diameter PBCA NPs was performed using polymerization at pH 2.0 with Dextran 70,000 as the stabilizer. Sulfo-HSAB spacers were used to covalently attach SOD and NR1 antibodies to the dextran-coated NPs. The prepared protein-NP conjugates possessed SOD activity and were capable of binding to rat cerebellar neurons. Thus, SOD and NR1 antibodies may be simultaneously attached to PBCA NPs while retaining at least a fraction of enzymatic activity and receptor-binding ability. The conjugates showed neuroprotective efficacy in vitro with rat cerebellar cell cultures challenged by superoxide.

Enzyme-nanoparticle conjugates for biomedical applications.

Enzymes hold a great promise as therapeutic agents because of their unique specificity and high level of activity. Yet, clinically important enzyme drugs are for less common than conventional low molecular weight drugs due to a number of disadvantages. Most important among these are poor stability, potential immunogenicity, and potential systemic toxicity. Recent developments in synthesis and characterization of nanoparticles and exciting novel properties of some classes of nanomaterials have boosted interest in the potential use of nanoparticles as carriers of enzyme drugs. In certain cases, use of enzymes attached to nanoparticles can help to overcome some of the above problems and improve the prospects of clinical applications of enzyme drugs. Here, we review recent data on the use of nanoparticles as carriers for several clinically important enzyme drugs and discuss advantages and potential limitations of such constructs. While promising preliminary results were obtained with regard to their performance in vitro and in some animal models, further investigations and clinical trials, as well as addressing regulatory issues, are warranted to make these delivery systems suitable for clinical applications.