Surface-modified mesoporous ceramics as delivery vehicle for haemoglobin

Aquasomes, a new drug delivery system comprised of surface-modified nanocrystalline ceramic carbohydrate composites, was developed to serve as haemoglobin carrier for oxygen delivery. The hydroxy-apatite ceramic core was prepared by coprecipitation and self-precipitation and coated with various sugars like cellobiose, maltose, sucrose, and trehalose. The effect of drying methods, i.e., air drying, vacuum drying, and lyophilization, on the degree of binding was studied by concanavalin-induced aggregation method. Haemoglobin was adsorbed over the sugar-coated ceramics, and percent loading was estimated by benzidine method. The adsorption of sugars on calcium hydro-apatite powder and haemoglobin adsorption on sugar-adsorbed ceramic followed both Freundlich and Langmuir isotherm. The haemoglobin aquasome formulations (equivalent to 7.5% Hb) were suspended in a phosphate buffer containing 7.5% w/v albumin and 0.01% w/v lecithin, and they were evaluated for oxygen-carrying capacity, which was found to be similar to fresh blood. The Hill coefficients were found to be fairly good for its use as oxygen carrier. The haemoglobin aquasome formulations did not induce haemolysis of red blood cells nor alter the blood coagulation time. The haemoglobin content of the formulation remained unchanged on storage for 30 days. The haemoglobin desorption was fairly low under shear conditions, indicating good stability of formulation in biological system. During in vivo study in rats the survivals were monitored as function of hematocrit in rats receiving isovolemic exchange transfusion. Arterial blood pressure and heart rate did not change significantly in animals transfused with aquasomal suspension on 50% exchange transfusion.