Fatty Acid–RGD Peptide Amphiphile Micelles as Potential Paclitaxel Delivery Carriers to αvβ3Integrin Overexpressing Tumors

Abstract

To design and synthesize fatty acid-RGD peptide amphiphiles with ADA linker for their potential delivery of hydrophobic drugs like paclitaxel targeted to α(v)β(3) integrin overexpressing tumors. Four amphiphiles - C16 or C18 fatty acid-RGD peptide and ADA linker were designed and synthesized. CMC, size and zeta potential of the amphiphiles were determined. FITC loaded micelles uptake into A2058 melanoma cells was investigated at 4°C and 37°C using confocal microscopy. Paclitaxel was loaded into micelles, their encapsulation efficiency and cytotoxicity of micelles was evaluated. The stability of the micelles was determined using FRET method. Mass, (1)H NMR and HPLC analysis confirmed the formation of amphiphiles and their purity. Among the amphiphiles, C18-(ADA)(2)-RGD amphiphile exhibited lowest CMC (9.00 ± 1.73 μM) and its micelles had suitable size (194.63 ± 44.86 nm) and zeta potential (0.27 ± 1.96 mV) for targeting. The cellular uptake of the micelles was temperature dependent and the micelles were stable. The IC50 of paclitaxel loaded in micelles decreased 50% in α(v)β(3) integrin overexpressing cells and showed a 4 fold increase in normal cells when compared to free paclitaxel. Amphiphiles of fatty acids-ADA-RGD were synthesized. These amphiphiles formed stable micelles and were effective as targeted delivery carriers to α(v)β(3) integrin overexpressing tumors.