In Vitro Drug Release from Macromolecule-Drug Conjugates of 3’(-7-Carboxyheptanoyl)-5-fluoro-2’-deoxyuridine with Decylenediamine-dextran T70 of Poly-L-lysine

Abstract

3’-(7-Carboxyheptanoyl)-5-fluoro-2’-deoxyuridine (C6-FUdR) was conjugated to decylenedi-amine-dextran T70 (T70-C10) or poly-L-lysine (PLL) by using l-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (EDC). Drug release patterns from the conjugates between C6-FUdR and T70-C10 (T70-C10-C6-FUdR) or PLL (PLL-C6-FUdR) by enzymatic and nonenzymatic processes were investigated at neutral and weakly acidic pHs. Under the nonenzymatic conditions, 5-fluoro-2’-deoxyuridine (FUdR) was released slowly only at neutral pH. This property is similar to that of C6-FUdR. Gradual drug release was observed enzymatically from T70-C10-C6-FUdR at both pHs, while PLL-C6-FUdR did not show enzymatic drug release. However, after the treatment of PLL-C6-FUdR with trypsin, FUdR was released enzymatically from the products; in this case, the release rate of FUdR was faster at neutral pH than at the weakly acidic pH. However, the release of FUdR by enzymatic processing was much slower from these conjugates than from C6-FUdR. © 1987, The Pharmaceutical Society of Japan. All rights reserved.