PMPC Modified PAMAM Dendrimer Enhances Brain Tumor-Targeted Drug Delivery.

Abstract

The excellent biocompatibility drug delivery system for effective treatment of glioma is still greatly challenged by the existence of blood-brain barrier, blood-brain tumor barrier, and the tissue toxicity caused by chemotherapy drugs. In this study, poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) is used for the first time for modifying third-generation poly(amidoamine) (PAMAM) to enhance their brain tumor-targeted drug delivery ability as well as simultaneously reducing the toxicity of PAMAM dendrimers and the tissue toxicity of the loaded doxorubicin (DOX). The cytotoxicity, the therapeutic ability in vitro, and the brain tumor-targeted ability of the PMPC modified PAMAM nanoparticles are further studied. Results indicate that PMPC, as a dual-functional modifier, can significantly reduce the cytotoxicity of PAMAM dendrimers, while efficiently target the brain tumor. In addition, the therapeutic effect of DOX-loaded PAMAM-PMPC in mice inoculated with U-87 is also studied in vivo. In comparison with DOX solution, DOX-loaded PAMAM-PMPC alleviates weight loss of tumor-inoculated mice and reduces the cardiotoxicity of DOX. The tumor growth inhibition, in vivo, is significantly increased up to (80.76 ± 1.66)%. In conclusion, this strategy of PMPC dual-functional targeted nanocarrier provides a new method for the delivery of chemotherapeutic drugs to treat glioma.

• Authors: Jiamin Ban, Sidi Li, Qi Zhan, Xuepin Li, Huike Xing, Ning Chen, Lixia Long, Xin Hou, Jin Zhao, Xubo Yuan
• Journal: Macromolecular bioscience (Macromol Biosci) Vol. 21 Issue 4 Pg. e2000392 (04 2021) ISSN: 1616-5195 [Electronic] Germany
• PMID: 33506646 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 Wiley-VCH GmbH.

Chemical References

• Dendrimers
• Drug Carriers
• PAMAM Starburst
• Polymethacrylic Acids
• poly(2-methacryloyloxyethyl-phosphorylcholine)
• Phosphorylcholine
• Doxorubicin

Topics

• Animals
• Blood-Brain Barrier (drug effects)
• Brain Neoplasms (drug therapy)
• Cell Line, Tumor
• Dendrimers (chemistry, pharmacology)
• Doxorubicin (administration & dosage, chemistry)
• Drug Carriers (therapeutic use)
• Drug Delivery Systems
• Drug Liberation
• Glioma (drug therapy)
• Humans
• Light
• Magnetic Resonance Spectroscopy
• Mice
• Nanoparticles
• Phosphorylcholine (analogs & derivatives, chemistry)
• Polymethacrylic Acids (chemistry)
• Scattering, Radiation
• Time Factors