Physicochemical properties of albumin microspheres determined by spectroscopic studies.

The interactions of a family of fluorescein dyes of varying hydrophobicities and polarizabilities (as well as those of several model drugs) with native and colloidal denatured albumin systems from various sources were monitored spectroscopically. The use of colloidal denatured albumin systems allowed direct determination of spectral shifts induced by the interactions of the dyes or drugs with the albumins. Large bathochromic shifts were observed upon interaction of hydrophobic dyes or drugs with bovine and human albumin systems. Egg albumin systems, on the other hand, did not induce such shifts. The hydrophobicities of the albumin surfaces estimated using bathochromic shifts were in the order bovine greater than human greater than egg, in agreement with literature values. The changes in absorbances of the dyes or drugs following interaction with the albumins allowed estimation of the polarizabilities of the albumins; these were in the order bovine greater than human greater than egg. The similar interactions of dyes and model drugs with albumin microspheres suggest that fluorescein dyes serve as excellent probes of the physicochemical state of denatured albumin systems and as good models for studying drug interaction with albumin microspheres. These studies also indicate that it may be possible to predict drug uptake by albumin microspheres from physicochemical properties of the drugs and carriers. Such predictions would be of great potential value for screening the suitability of carriers, especially for drugs which are highly sensitive to the preparation conditions of the microspheres, such as heating and cross-linking agents.