CONTROL OF MOLECULAR POLYMORPHISMS BY A STRUCTURED CARBOHYDRATE CERAMIC DELIVERY VEHICLE - AQUASOMES/

Molecular denaturation of polypeptides and other macromolecular pharma ceuticals upon surface adsorption from an aqueous environment is almos t inevitable. Molecular denaturation, coupled with a net increase in e ntropy, accounts for the net negative Delta G and frequent irreversibl e nature of surface adsorption. The consequence of this interaction is that surface immobilized drugs lose their dynamic freedom and thus, a ll too often, their biological activity. A drug delivery system based on a novel surface modification process to help reverse the constraini ng activity of surfaces is described. Beginning with preformed carbon ceramic nanoparticles and self-assembled calcium-phosphate dihydrate p articles (colloidal precipitation) to which glassy carbohydrates are t hen allowed to adsorb as a nanometer thick surface coating, a molecula r carrier is formed. The carbohydrate coating functions as a dehydropr otectant and stabilizes subsequently non-covalently bound immobilized members of biochemically reactive surface members such as pharmaceutic als. Many of the physical properties of this enabling system have been characterized in vitro and in animal models. Antigen delivery. drug d elivery, and hemoglobin delivery experiments are described.