CONFORMATIONALLY STABILIZING SELF-ASSEMBLING NANOSTRUCTURED DELIVERY VEHICLES FOR BIOCHEMICALLY REACTIVE PAIRS

Molecular denaturation of polypeptides and other macromolecules upon s urface adsorption from an aqueous environment is almost inevitable. Mo lecular denaturation, coupled with a net increase in entropy, accounts for the net negative Delta G and frequent irreversible nature of surf ace adsorption. Real world complications arising from this fundamental biophysical problem include marine fouling of ships' hulls, the progr essive obstruction of sewer pipes, inactivated pharmaceutical agents a nd adverse biological reactions to implanted medical devices. Using se lf-assembled nanocrystalline particulates with polyhydroxyloligomeric surface films, much of this surface-induced denaturation appeals to ha ve been arrested. Beginning with preformed carbon ceramic nanoparticle s and self-assembled calcium-phosphate dihydrate particles (colloidal precipitation) to which glassy carbohydrates are then allowed to adsor b as a nanometer thick surface coating, a molecular carrier is formed. The carbohydrate coating functions as a dehydroprotectant and stabili zes subsequently non-covalently bound immobilized members of biochemic ally reactive surface pairs. The final synthetic product consists of t hree layers. The core is comprised of the ceramic, the second layer is the dehydroprotectant polyhydroxyloligomer adhesive, and the surface layer is the biochemically reactive molecule for which delivery is des ired. Many of the physical properties of this enabling system have bee n characterized in vitro and in animal models. By all measures at pres ent, the favorable physical properties and biological behavior of the molecular transportation assembly point to an exciting new interdiscip linary are a of technology development in materials science, chemistry and biology.