Blood levels and serum protein binding of cis-Platinum(II) complexed to carboxymethyl-dextran

Abstract

Plasma levels and serum protein binding of cis-diamminedichloroplatinum(II) (cis-DDP) or cis-diamminediaquoplatinum(II) (cis-aq) complexed to carboxymethyl-dextran (CM-dex) with a molecular weight of 10,000 (T-10), 40,000 (T-40), and 250,000 (T-250) were investigated in BALB/c mice. Levels of active drug in the circulation after the i.v. or i.p. administration of the free or complexed drugs, as well as the loss of drug activity due to serum protein binding following incubation with mouse serum, were monitored by an antitumor in vitro assay using a drug-sensitive tumor cell line. Following i.v. injection of the complexes, active platinum(II) was maintained in the circulation at higher levels and for a longer period, whereas the free drug disappeared rapidly. The rate of disappearance of the complexed drug from the circulation was markedly influenced by the molecular size of the carrier CM-dex, since the retained amount of drug was considerably higher with the T-40 and T-250 complexes than with the T-10 complex. An i.p. injection resulted in a rapid and transient appearance of low levels of the free drugs in the blood, whereas in the case of the complexes, transport to the circulation was slower and their maintenance in the blood system was markedly higher. Serum protein binding was much slower with CM-dex-complexed drugs (regardless of the molecular size of the CM-dex carrier) than with the free drugs.

Multifunctional Poly(ethylene glycol)s

“…[118] Many of its drawbacks, such as acute nephrotoxicity and chronic neurotoxicity, rapid inactivation in the plasma, and poor solubility in water can characteristically be reduced Poly(ethylene glycol)s through polymer conjugation. [119,120] In 2010 Zhou et al reported the preparation of an anticancer polymer-drug conjugate, for the first time based on the biocompatible random hydroxy mf-PEG P(EO-co-G), obtained by copolymerization of EO and EEGE and subsequent removal of the acetal protective groups. [95] Modification of the hydroxy groups with malonate derivatives allowed for the reversible conjugation of cisplatin through a six-membered, chelate-type dicarboxylate coordination bond (Scheme 2).…”

Biamphiphilic triblock copolymer micelles as a multifunctional platform for anticancer drug delivery

“…The absorbance was measured with a UV‐visible spectrophotometer at 485 nm 22. Quantitative determination of CDDP was performed in double distilled water 48. One milliliter of the sample solution was mixed with 1 mL of o ‐phenylenediamine (OPDA) solution (1.2 mg/mL in DMF).…”

“…22 Quantitative determination of CDDP was performed in double distilled water. 48 One milliliter of the sample solution was mixed with 1 mL of ophenylenediamine (OPDA) solution (1.2 mg/mL in DMF). Then the mixture was placed in a 100 C water bath for 10 min and the absorbance of the solution was measured at…”

Multifunktionelle Poly(ethylenglycole)

“…[118] Viele der Nachteile wie akute Nieren-oder chronische Neurotoxizität, schnelle Desaktivierung im Plasma und schlechte Wasserlçs-lichkeit kçnnen durch Konjugation mit Polymeren überwun-den oder reduziert werden. [119,120] Zhou und Chau beschrieben 2010 die Herstellung eines Polymer-Wirkstoff-Konjugats zur Krebstherapie, das erstmals auf einem Hydroxy-mf-PEG (P-(EO-co-G)) basiert. [95] Dieses wurde durch Copolymerisation von EO und EEGE und anschließende Entschützung synthetisiert.…”