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

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ABSTRACT

Purpose

To design and synthesize fatty acid-RGD peptide amphiphiles with ADA linker for their potential delivery of hydrophobic drugs like paclitaxel targeted to αvβ3 integrin overexpressing tumors.

Methods

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.

Results

Mass, 1H 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 αvβ3 integrin overexpressing cells and showed a 4 fold increase in normal cells when compared to free paclitaxel.

Conclusion

Amphiphiles of fatty acids–ADA-RGD were synthesized. These amphiphiles formed stable micelles and were effective as targeted delivery carriers to αvβ3 integrin overexpressing tumors.

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Authors and Affiliations

  1. Department of Pharmaceutics & Medicinal Chemistry, Thomas. J. Long School of Pharmacy & Health Sciences, University of the Pacific, Stockton, California, USA

    Narashima Murthy Javali, April Raj, Poonam Saraf, Xiaoling Li & Bhaskara Jasti

  2. Department of Biological Sciences, University of the Pacific, Stockton, California, USA

    April Raj

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  1. Narashima Murthy Javali
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  2. April Raj
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  5. Bhaskara Jasti
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Correspondence to Bhaskara Jasti.

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Javali, N.M., Raj, A., Saraf, P. et al. Fatty Acid–RGD Peptide Amphiphile Micelles as Potential Paclitaxel Delivery Carriers to αvβ3Integrin Overexpressing Tumors. Pharm Res 29, 3347–3361 (2012). https://doi.org/10.1007/s11095-012-0830-5

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