Targeted delivery of insoluble cargo (paclitaxel) by PEGylated chitosan nanoparticles grafted with Arg-Gly-Asp (RGD).

Abstract

Poor delivery of insoluble anticancer drugs has so far precluded their clinical application. In this study, we developed a tumor-targeting delivery system for insoluble drug (paclitaxel, PTX) by PEGylated O-carboxymethyl-chitosan (CMC) nanoparticles grafted with cyclic Arg-Gly-Asp (RGD) peptide. To improve the loading efficiency (LE), we combined O/W/O double emulsion method with temperature-programmed solidification technique and controlled PTX within the matrix network as in situ nanocrystallite form. Furthermore, these CMC nanoparticles were PEGylated, which could reduce recognition by the reticuloendothelial system (RES) and prolong the circulation time in blood. In addition, further graft of cyclic RGD peptide at the terminal of PEG chain endowed these nanoparticles with higher affinity to in vitro Lewis lung carcinoma (LLC) cells and in vivo tumor tissue. These outstanding properties enabled as-designed nanodevice to exhibit a greater tumor growth inhibition effect and much lower side effects over the commercial formulation Taxol.

• Authors: Pi-Ping Lv, Yu-Feng Ma, Rong Yu, Hua Yue, De-Zhi Ni, Wei Wei, Guang-Hui Ma
• Journal: Molecular pharmaceutics (Mol Pharm) Vol. 9 Issue 6 Pg. 1736-47 (Jun 04 2012) ISSN: 1543-8392 [Electronic] United States
• PMID: 22559746 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Drug Carriers
• Emulsions
• Oligopeptides
• arginyl-glycyl-aspartic acid
• Chitosan
• Paclitaxel

Topics

• Animals
• Cell Line, Tumor
• Chitosan (chemistry)
• Drug Carriers (chemistry)
• Emulsions (chemistry)
• Injections, Intravenous
• Lung Neoplasms (drug therapy)
• Male
• Mice
• Mice, Inbred C57BL
• NIH 3T3 Cells
• Nanoparticles (chemistry)
• Oligopeptides (chemistry)
• Paclitaxel (chemistry, therapeutic use)