Polymeric micelles for enhanced lymphatic drug delivery to treat metastatic tumors.

Abstract

Polymeric micelles have been proven to be a promising nano-sized system for drug delivery. Understanding its in vivo behaviors at the whole body, tissue and cellular levels is critical for translating this drug delivery system into clinical practice. In this study, the 14.5 nm micelles made of polyethylene glycol-phosphatidylethanolamine (PEG-PE) for delivery of doxorubicin and vinorelbine were investigated. Using confocal and two-photon microscopy imaging of live mice or tissue sections, we observed that after systemic administration, the fluorescently labeled PEG-PE micelles encapsulating doxorubicin migrated through blood vessels in entirety into the interstitial tissue, collected by lymphatic vessels, and accumulated in lymph nodes. Importantly, encapsulated drugs such as vinorelbine (Nanovin), preferentially accumulate in lymph nodes when compared to the free drugs. Moreover, the in vivo bioluminescent imaging showed that Nanovin significantly reduced lymph node metastasis rate (P<0.05) in 4 T1-luc2 murine breast tumor bearing mice. Finally, we observed that Nanovin enhanced antitumor activity against primary tumors and lung metastases while having low toxicity in various 4 T1 tumor models. This study suggests that PEG-PE micelle is a promising drug delivery system for the treatment of lymphatic metastases, and may also have important applications in other lymphatic system-related diseases.

• Authors: Lei Qin, Fayun Zhang, Xiaoyan Lu, Xiuli Wei, Jing Wang, Xiaocui Fang, Duanyun Si, Yiguang Wang, Chunling Zhang, Rong Yang, Changxiao Liu, Wei Liang
• Journal: Journal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 171 Issue 2 Pg. 133-42 (Oct 28 2013) ISSN: 1873-4995 [Electronic] Netherlands
• PMID: 23863448 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013.

Chemical References

• Antineoplastic Agents, Phytogenic
• Micelles
• Phosphatidylethanolamines
• dioleoyl-N-(monomethoxypolyethylene glycol succinyl)phosphatidylethanolamine
• Polyethylene Glycols
• Vinblastine
• Vinorelbine

Topics

• Animals
• Antineoplastic Agents, Phytogenic (administration & dosage, chemistry)
• Drug Delivery Systems
• Female
• Humans
• Lung Neoplasms (drug therapy, secondary)
• Lymph Nodes (metabolism)
• Lymphatic Metastasis (prevention & control)
• Mammary Neoplasms, Animal (drug therapy, pathology)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Micelles
• Phosphatidylethanolamines (chemistry)
• Polyethylene Glycols (chemistry)
• Tumor Burden (drug effects)
• Vinblastine (administration & dosage, analogs & derivatives, chemistry)
• Vinorelbine