Cell-mediated transfer of catalase nanoparticles from macrophages to brain endothelial, glial and neuronal cells.

Background: Our laboratories forged the concept of macrophage delivery of protein antioxidants to attenuate neuroinflammation and nigrostriatal neurodegeneration in Parkinson's disease. Notably, the delivery of the redox enzyme, catalase, incorporated into a polyion complex micelle ('nanozyme') by bone marrow-derived macrophages protected nigrostriatum against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine intoxication. Nonetheless, how macrophage delivery of nanozyme increases the efficacy of catalase remains unknown.

The modification of siRNA with 3' cholesterol to increase nuclease protection and suppression of native mRNA by select siRNA polyplexes.

Polymer-siRNA complexes (siRNA polyplexes) are being actively developed to improve the therapeutic application of siRNA. A major limitation for many siRNA polyplexes, however, is insufficient mRNA suppression. Given that modifying the sense strand of siRNA with 3' cholesterol (chol-siRNA) increases the activity of free nuclease-resistant siRNA in vitro and in vivo, we hypothesized that complexation of chol-siRNA can increase mRNA suppression by siRNA polyplexes.

Effects of the PPARgamma agonist troglitazone on endothelial cells in vivo and in vitro: differences between human and mouse.

Peroxisome proliferator-activated receptor gamma (PPARgamma) agonists and PPARgamma/alpha dual agonists have been or are being developed for clinical use in the treatment of type 2 diabetes mellitus and hyperlipidemias. A common tumor finding in rodent carcinogenicity studies for these agonists is hemangioma/hemangiosarcoma in mice but not in rats. We hypothesized that increased endothelial cell proliferation may be involved in the mechanism of PPAR agonist-induced vascular tumors in mice, and we investigated the effects on endothelial cells utilizing troglitazone, the first clinically used PPARgamma agonist, in vivo and in vitro.

Formulations of biodegradable Nanogel carriers with 5'-triphosphates of nucleoside analogs that display a reduced cytotoxicity and enhanced drug activity.

Therapies including nucleoside analogs are associated with severe toxic side effects and acquirement of drug resistance. We have previously reported the drug delivery in the form of 5'-triphosphates (NTP) encapsulated in cross-linked cationic networks of polyethylenimine (PEI) and PEG/Pluronic polymers (Nanogels). In this study, Nanogels, containing biodegradable PEI that could easily dissociate in reducing cytosolic environment and form products with minimal toxicity, were synthesized and displayed low cytotoxicity.