Trans-tissue, sustained release of gemcitabine from photocured gelatin gel inhibits the growth of heterotopic human pancreatic tumor in nude mice.

Abstract

PURPOSE:

Although gemcitabine, a deoxycytidine analogue, recently demonstrated improvements in the response rate for pancreatic cancer, the median survival for patients is limited to 4-6 months. The purpose of the present study was to develop trans-tissue delivery of gemcitabine, which is based on photocured gelatin gel immobilized with gemcitabine, and to validate whether such a system inhibits the growth of the pancreatic tumor in vivo.

EXPERIMENTAL DESIGN:

The in vitro release profile of gel-embedded gemcitabine from a gel was examined based on in vitro chemosensitivity of AsPC1 cell (human pancreatic cancer cell line) for gemcitabine. The permeation of gel-embedded rhodamine B (used as a model drug) into tissues and inhibitory effect of tumor growth of photocured gelatin gel immobilized with gemcitabine were examined using in vivo s.c. tumor model of athymic mice.

RESULTS:

The release profile was characterized as an initial burst of release, followed by a gradual release, irrespective of gelatin concentration. Rhodamine B permeated into the tumor and retained for at least 10 days. Photocured gelatin gel immobilized with gemcitabine significantly reduced the tumor volume compared with gemcitabine injection. Therapeutic success was correlated with decreased cell proliferation and increased cell apoptosis in tumor cells, supported by proliferating cell nuclear antigen and terminal deoxynucleotidyltransferase-mediated nick end labeling staining. Blood analysis and body weight measurement showed that little side effect was observed in this therapy.

CONCLUSIONS:

In situ trans-tissue gemcitabine delivery on the tissue with possibly remnant cancer cells using the drug-releasing matrix developed here is expected to reduce the rate of local recurrence for patients with pancreatic cancer.

• Authors: Hidenobu Okino, Ryo Maeyama, Tatsuya Manabe, Takehisa Matsuda, Masao Tanaka
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 9 Issue 15 Pg. 5786-93 (Nov 15 2003) ISSN: 1078-0432 [Print] United States
• PMID: 14654564 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antimetabolites, Antineoplastic
• Delayed-Action Preparations
• Deoxycytidine
• Gelatin
• Gemcitabine

Topics

• Animals
• Antimetabolites, Antineoplastic (pharmacokinetics, therapeutic use)
• Apoptosis (drug effects)
• Cell Division (drug effects)
• Cell Line, Tumor
• Delayed-Action Preparations
• Deoxycytidine (analogs & derivatives, pharmacokinetics, therapeutic use)
• Gelatin (radiation effects)
• Humans
• Mice
• Mice, Nude
• Pancreatic Neoplasms (drug therapy, pathology)
• Tissue Distribution
• Transplantation, Heterologous
• Gemcitabine