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  • Title: Albumin-based drug carriers: comparison between serum albumins of different species on pharmacokinetics and tumor uptake of the conjugate.
    Author: Stehle G, Wunder A, Schrenk HH, Hartung G, Heene DL, Sinn H.
    Journal: Anticancer Drugs; 1999 Sep; 10(8):785-90. PubMed ID: 10573211.
    Abstract:
    Albumin-based drug carrier systems have been developed in the field of chemotherapy to improve the passive tumor targeting properties of anti-cancer drugs. Usually, serum albumins of different species are used as carrier proteins, mostly of bovine (BSA), human (HSA) or rat (RSA) origin. The resulting albumin conjugates are often tested for anticancer activity in heterologous tumor models. No data is available whether the choice of the albumin species might influence the pharmacokinetics or the tumor uptake rates of the conjugates in vivo. Residualizingly ([111In]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 rates of the three albumin tracers. The tumors were the major catabolic sites accumulating 14-18% of the injected dose (ID). Low hepatic uptake rates were determined for all albumins (below 100% ID). Minor differences were found 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 commercial preparation or the radiolabeling of the different batches. In addition, 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 or BSA might not decisively influence the results of drug targeting experiments 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 well tolerated without signs of allergy or anaphylaxis.
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