ALBUMIN MICROSPHERES AS A DRUG-DELIVERY SYSTEM - RELATION AMONG TURBIDITY RATIO, DEGREE OF CROSS-LINKING, AND DRUG-RELEASE

The degree of cross-linking of albumin microspheres, with and without drug, was assessed using turbidity measurements carried out in the pre sence of water and the protein denaturant guanidine hydrochloride (GuH Cl) at a concentration that disrupted noncovalent bonds while having n o effect on covalent bonds. The measurements allowed calculation of a turbidity ratio (T(G)/T(W)), expressed as the ratio of the turbidity o f albumin microspheres in 6 M GuHCl (T(G)) divided by that in water (T (W)). A linear relation existed between T(G)/T(W) and the (i) temperat ure at which the microspheres were prepared, (ii) concentration of the cross-linking agent glutaraldehyde, and (iii) time of exposure to a s econd cross-linking agent, formaldehyde vapor, three conditions that i ncrease the degree of cross-linking. The turbidity ratio also increase d as the concentration of the albumin solution used to prepare the mic rospheres increased from 25 to 50%. Drug release from the microspheres consisted of an initial, rapid, burst followed by a second, slower, p hase. The rates in both release phases were inversely related to the t urbidity ratio, suggesting that this parameter has utility as an indic ator of the degree of cross-linking in albumin microspheres.