Biodistribution of free and N-(2-hydroxypropyl)methacrylamide copolymer-bound mesochlorin e(6) and adriamycin in nude mice bearing human ovarian carcinoma OVCAR-3 xenografts.

Abstract

The purpose of this study was to examine the biodistribution of the photosensitizing drug, mesochlorin e(6) monoethylenediamine (Mce(6)), and the antineoplastic agent, adriamycin (ADR), as well as their N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer conjugates in female nu/nu athymic mice bearing human ovarian carcinoma OVCAR-3 xenografts. The levels of Mce(6) and HPMA copolymer-bound Mce(6) in tissues were assayed spectrophotometrically, while the levels of ADR and HPMA copolymer-bound ADR were determined using high-performance liquid chromatography. It appeared that the circulation lifetimes of HPMA copolymer-bound Mce(6) and ADR were three times more than those of the drugs in the free form. The concentrations of the HPMA copolymer-conjugated drugs in tumor reached maximum levels 18 h post injection. Intravenous injection routinely gave higher tissue levels of the drugs than intraperitoneal administration at time intervals less than 24 h. The biodistribution of the HPMA copolymer-bound drugs in tumor-bearing mice was significantly different from that of the free drugs, which is important in optimizing the treatment protocols. In particular, the HPMA copolymer-conjugated drugs accumulated at significantly higher levels in tumor tissues. This effect is attributed to the increased vascular permeability and reduced lymphatic drainage characteristic of tumor tissues [enhanced permeability and retention (EPR) effect].

• Authors: J J Shiah, Y Sun, C M Peterson, J Kopecek
• Journal: Journal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 61 Issue 1-2 Pg. 145-57 (Aug 27 1999) ISSN: 0168-3659 [Print] Netherlands
• PMID: 10469911 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antineoplastic Agents
• Methacrylates
• Photosensitizing Agents
• Porphyrins
• Doxorubicin
• hydroxypropyl methacrylate

Topics

• Animals
• Antineoplastic Agents (administration & dosage, pharmacokinetics)
• Doxorubicin (administration & dosage, pharmacokinetics)
• Female
• Humans
• Methacrylates (administration & dosage)
• Mice
• Mice, Nude
• Neoplasm Transplantation
• Ovarian Neoplasms (metabolism)
• Photochemotherapy
• Photosensitizing Agents (administration & dosage, pharmacokinetics)
• Porphyrins (administration & dosage, pharmacokinetics)
• Tissue Distribution
• Transplantation, Heterologous