MPEG-DSPE polymeric micelle for translymphatic chemotherapy of lymph node metastasis.

Abstract

Lymph node metastasis is one of the major pathways for tumor formation and it is difficult to deliver chemotherapeutics at therapeutic concentrations to lymph node metastasis. This study prepared methyl poly(ethylene glycol)-distearoylphosphatidylethanolamine/doxorubicin (MPEG-DSPE/DOX) micelle for the treatment of lymph node metastasis. The MPEG-DSPE/DOX micelle prepared were of spherical morphology with a particle size of 20 ± 5 nm. The uptake rates of DOX and MPEG-DSPE/DOX micelle by A375 cells were 51.2% and 88.7%, respectively. The phagocytosis rate of MPEG-DSPE/Rhodamine B micelle by RAW264.7 cells was 17.2-fold lower than for Rhodamine B alone. After subcutaneous injection, MPEG-DSPE micelle underwent lymphatic absorption and accumulated in popliteal lymph nodes. MPEG-DSPE/DOX micelle significantly alleviated damage to the subcutaneous tissue of the injection sites compared with DOX alone. We established a model of nude mice bearing lymph node metastasis of A375 cells. After subcutaneous injection, the weights of both the popliteal and iliac lymph nodes of the MPEG-DSPE/DOX micelle group were significantly lower than in the saline and DOX groups. MPEG-DSPE/DOX micelle effectively killed the tumor cells in popliteal and iliac lymph nodes. In conclusion, MPEG-DSPE micelle is a promising drug delivery system for the treatment of lymph node metastasis.

• Authors: Xue Li, Qing Dong, Zhiqiang Yan, Weiyue Lu, Lingling Feng, Cao Xie, Zuoxu Xie, Bingxia Su, Min Liu
• Journal: International journal of pharmaceutics (Int J Pharm) Vol. 487 Issue 1-2 Pg. 8-16 (Jun 20 2015) ISSN: 1873-3476 [Electronic] Netherlands
• PMID: 25841567 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Antibiotics, Antineoplastic
• Micelles
• Phosphatidylethanolamines
• polyethylene glycol-distearoylphosphatidylethanolamine
• Polyethylene Glycols
• Doxorubicin

Topics

• Animals
• Antibiotics, Antineoplastic (administration & dosage, pharmacokinetics, therapeutic use)
• Cell Line, Tumor
• Doxorubicin (administration & dosage, pharmacokinetics, therapeutic use)
• Drug Delivery Systems
• Humans
• Lymph Nodes (metabolism)
• Lymphatic Metastasis
• Macrophages (drug effects)
• Male
• Mice
• Mice, Nude
• Micelles
• Microspheres
• Particle Size
• Phagocytosis (drug effects)
• Phosphatidylethanolamines
• Polyethylene Glycols
• Rats
• Rats, Wistar