Albumin-based drug carriers: comparison between serum albumins of different species on pharmacokinetics and tumor uptake of the conjugate

Albumin-based drug carrier systems have been developed in the field of chem otherapy to improve the passive tumor targeting properties of anti-cancer d rugs. Usually, serum albumins of different species are used as carrier prot eins, mostly of bovine (BSA), human (HSA) or rat (RSA) origin. The resultin g albumin conjugates are often tested for anticancer activity in heterologo us tumor models, No data is available whether the choice of the albumin spe cies might influence the pharmacokinetics or the tumor uptake rates of the conjugates in vivo. Residualizingly ([In-111]DTPA) radiolabeled RSA, BSA or HSA were administered to Walker-256 carcinoma-bearing rats. No significant difference was found in the absolute or the weight-adjusted tumor uptake r ates of the three albumin tracers. The tumors were the major catabolic site s accumulating 14-18% of the injected dose (ID). Low hepatic uptake rates w ere determined for all albumins (below 10% ID), Minor differences were foun d for hepatic uptake in favor of the autologous RSA (5.8% ID) versus HSA (6 .9%) and BSA (8.0%). These differences might have occurred during the comme rcial preparation or the radiolabeling of the different batches. In additio n, there are structural differences between the three albumins, which might have contributed, despite high sequence homologies above 70% for RSA, HSA and BSA, These minor differences in the distribution patterns of RSA, HSA o r BSA might not decisively influence the results of drug targeting experime nts in rats. For further studies with albumin conjugates, HSA was chosen as drug carrier in rodent animal models when considering later human use. In rats or nude mice multiple injections of various HSA-drug conjugates were w ell tolerated without signs of allergy or anaphylaxis. [(C) 1999 Lippincott Williams & Wilkins].