Comparison of albumin and casein microspheres as a carrier for doxorubicin.

Doxorubicin (Adriamycin)-loaded casein and albumin microspheres, with diameters between 14 and 38 micron (50% weight average) were prepared by glutaraldehyde stabilization of the aqueous phase (containing protein and drug) of a water in oil emulsion. Physical properties, drug loading characteristics and release rates from microspheres in-vitro have been compared and correlated with effects on tumour growth when injected intratumourally in rats. Compared with albumin, the surface charge of the casein system was more negative and the microspheres exhibited a slower release of drug in-vitro. Both observations could be explained by the lower drug content of the casein system. There was evidence for the formation of a doxorubicin complex in the microspheres, the significance of which is not yet known. Casein microspheres containing 11 micrograms of doxorubicin had a similar inhibitory effect on tumour growth (growth delay = 20.7 days) to 85 micrograms of drug incorporated into albumin microspheres (growth delay = 18.6 days). The absence of a simple dose-response relationship shows that carrier matrix can influence potency of incorporated drug. The results are consistent with release rate of the drug from microspheres (obversely, rate of drug delivery to the tumour), being a determinant of potency in these systems.