Arg-Gly-Asp (RGD) peptide conjugated poly(lactic acid)–poly(ethylene oxide) micelle for targeted drug delivery
✍ Scribed by Zhiyuan Hu; Fang Luo; Yifeng Pan; Can Hou; Lifeng Ren; Jiji Chen; Jiwei Wang; Yangde Zhang
- Book ID
- 102294175
- Publisher
- John Wiley and Sons
- Year
- 2008
- Tongue
- English
- Weight
- 319 KB
- Volume
- 85A
- Category
- Article
- ISSN
- 1549-3296
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✦ Synopsis
Abstract
In this study, a new poly(lactic acid)–poly (ethylene oxide)‐Arg‐Gly‐Asp (PLA‐PEO‐RGD) derivative was synthesized, and paclitaxel‐loaded PLA‐PEO‐RGD micelles were prepared by this derivative. The solubility assay showed that micelles mixed with Pluronic F‐68 as surfactant could increase the solubility of this hydrophobic paclitaxel in aqueous solution. The cell‐binding assay showed that PLA‐PEO‐RGD micelle (IC~50~ = 11.13 ± 1.38 nmol/L) had about 3.6‐fold higher integrin avidity than PLA‐PEO‐RGD conjugates (IC~50~ = 40.33 ± 3.12 nmol/L). The avidity of micelle was also higher than RGD4C peptide (IC~50~ = 24.44 ± 1.21 nmol/L). The in vitro drug release profile of drug‐loaded PLA‐PEO‐RGD micelles exhibited initial burst release to 37% ± 2% (w/w) during the first 12 h, and then the release rate became steady in a controlled release manner. Furthermore, treatment of the MDA‐MB‐435 breast cancer cell line with paclitaxel‐loaded PLA‐PEO‐RGD micelles yielded cytotoxicities, with EC~50~ values of ∼30 μmol/L. The paclitaxel‐loaded PLA‐PEO‐RGD micelles treated group showed the most dramatic tumor reduction in MDA‐MB‐435 tumor‐bearing nude mice, and the final mean tumor load was 31 ± 16 mm^3^ (mean ± SD; n = 8). ^125^I‐labeled micelles administration resulted in significant (p < 0.001) higher tumor uptake (2.68% ± 0.14%, ID/g) of PLA‐PEO‐RGD micelles compared to PLA‐PEO micelles (0.84% ± 0.09%, ID/g) after 2.5 h postinjection. Biodistribution study showed the best blood clearance of PLA‐PEO‐RGD micelles after 4.5 h postinjection. The results of this study suggest that paclitaxel‐loaded PLA‐PEO‐RGD micelles based on the specific recognition of α~V~β~3~ integrin represent a potential and powerful target delivery technology. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008