Authors:
Jay C Sy, Niren Murthy, and Michael E Davis
Summary:
Protein delivery from polymeric microparticles has seen limited success due to low loading efficiencies and loss of protein activity. We hypothesized that by utilizing protein purification techniques, we could efficiently load proteins onto the surface of polyketal microparticles while retaining activity. This was accomplished by incorporating a nitrilotriacetic acid (NTA)-lipid conjugate in our particle. To characterize the binding of Ni-NTA to His6-labeled protein, we investigated His-labeled green fluorescent protein (His-GFP) binding via fluorescent microscopy and quantitative analysis using ELISA. We found little nonspecific binding and a maximum loading of 40 ng His-GFP/mg particle (40% loading efficiency). This specific binding was reversed by incubation with 500 mM imidazole. Release studies under physiological conditions (10% fetal bovine serum, 37°C) demonstrated that 50% of the bound protein is released within 24h. Favorable release kinetics, combined with tunable hydrolysis of polyketals, make our particles ideal for use as a dual-drug delivery vehicles.
Source:
The 236th American Chemical Society National Meeting; Philadelphia, PA, Franklin 4 - 8, Poster, 6:00 PM-8:00 PM (08/18/08)