| 17896765 |
Hu Z, Luo F, Pan Y, Hou C, Ren L, Chen J, Wang J, Zhang Y: Arg-Gly-Asp (RGD) peptide conjugated poly (lactic acid)-poly (ethylene oxide) micelle for targeted drug delivery. J Biomed Mater Res A. 2008 Jun 1;85(3):797-807.
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 approximately 30 mumol/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 alpha (V) beta (3) integrin represent a potential and powerful target delivery technology. |
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