A single treatment with microcapsules containing a CXCR4 antagonist suppresses pulmonary metastasis of murine melanoma.
Biodegradable poly D,L-lactic acid (PLA, molecular weight: ca. 5000) microcapsules containing a CXCR4 antagonist (4F-benzoyl-TE14011) were prepared (4F-benzoyl-TE14011-PLA), and their anti-metastatic activity was evaluated in mice. A single subcutaneous administration of 4F-benzoyl-TE14011-PLA significantly reduced the number of colonies formed by pulmonary metastasis of B16-BL6 melanoma cells expressing CXCR4. The same dose of 4F-benzoyl-TE14011 in a single or a series of treatments affected little. The substance 4F-benzoyl-TE14011 dose-dependently suppressed B16-BL6 cell growth. In the cells cultured with SDF-1, a more potent suppression was observed. 4F-Benzoyl-TE14011 was rapidly released from 4F-benzoyl-TE14011-PLA for an initial period, both in vitro and in vivo. A steady release was thereafter observed. Therefore, this drug release profile might contribute to prevention of melanoma metastasis at the steps involving the migration and cell growth. These results also show that a sustained drug release formulation could be a useful drug delivery system for CXCR4 antagonists.
Takenaga
M
M
Institute of Medical Science, St. Marianna University School of Medicine, Kawasaki 216-8512, Japan. m2take@marianna-u.ac.jp
Tamamura
H
H
Hiramatsu
K
K
Nakamura
N
N
Yamaguchi
Y
Y
Kitagawa
A
A
Kawai
S
S
Nakashima
H
H
Fujii
N
N
Igarashi
R
R
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D003692:Delayed-Action Preparations / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000379:methods*; D007279:Injections, Subcutaneous; D019344:Lactic Acid / Q000737:chemistry; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology* / Q000556:secondary; D008297:Male; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology* / Q000556:secondary; D051379:Mice; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000008:administration & dosage*; D011091:Polyesters; D011108:Polymers / Q000737:chemistry; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016896:Treatment Outcome
C477728:4-fluorobenzoyl-TN-14003; D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D010455:Peptides; D011091:Polyesters; D011108:Polymers; D019718:Receptors, CXCR4; D019344:Lactic Acid; C033616:poly(lactide)