Hyaluronidase pretreatment produces selective melphalan enrichment in malignant melanoma implanted in nude mice

Cancer Chemotherapy and Pharmacology
I MuckenschnabelA Buschauer

Abstract

Preclinical and clinical observations suggest that the administration of hyaluronidase (Hyase) shortly before that of chemotherapy increases the access and, thus, the effectiveness of anticancer drugs in tumors. To examine this hypotheses as well as the selectivity of such a therapeutic approach potentially beneficial in isolated limb perfusion, the Hyase-induced distribution of melphalan was measured in tumor-bearing nude mice with respect to the mode of drug administration using RP-18 ion-pair high-performance liquid chromatography (HPLC) with fluorimetric detection. Melphalan alone (50 micromol/kg) or a combination of melphalan (50 micro mol/kg) and Hyase (100,000 IU/kg) was injected either i.p. or s.c. in the vicinity of the tumors. The s.c. melphalan injection caused a 4-fold rise in melphalan concentration (59 microM) in the tumors as compared with i.p. application (15 microM). Only minor effects were observed with respect to the route of melphalan application on its distribution in other tissues (ca. 13 microM in plasma, 15 microM in muscle, 30 microM in the liver, 26 microM in the kidney, and 21 microM in the testicle). Irrespective of the route of Hyase coadministration, the enzyme increased the concentration of i.p. i...Continue Reading

Citations

Mar 4, 2000·Journal of Pharmaceutical and Biomedical Analysis·K BrightmanC T Manktelow
Mar 28, 2003·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Martin OettlArmin Buschauer
Nov 5, 2011·Cancer Discovery·Clifford J WhatcottDaniel D Von Hoff
Jul 2, 2005·Expert Opinion on Investigational Drugs·I El-Hariry, M Pignatelli
Nov 21, 2007·Protein Expression and Purification·Stephan ReitingerGünter Lepperdinger
Nov 8, 2013·Aesthetic Surgery Journal·Maurizio CavalliniLuca Vaienti
Aug 24, 2013·Nanoscale·P ScodellerG J A A Soler-Illia
Mar 16, 2017·Biomaterials·Ronnie H FangLiangfang Zhang

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