Fatty acid-RGD peptide amphiphile micelles as potential paclitaxel delivery carriers to α(v)β₃ integrin overexpressing tumors.

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 α(v)β(3) 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, (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.

CONCLUSION:

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.

• Authors: Narashima Murthy Javali, April Raj, Poonam Saraf, Xiaoling Li, Bhaskara Jasti
• Journal: Pharmaceutical research (Pharm Res) Vol. 29 Issue 12 Pg. 3347-61 (Dec 2012) ISSN: 1573-904X [Electronic] United States
• PMID: 22825750 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents, Phytogenic
• Drug Carriers
• Fatty Acids
• Integrin alphaVbeta3
• Micelles
• Oligopeptides
• Surface-Active Agents
• arginyl-glycyl-aspartic acid
• Paclitaxel

Topics

• Antineoplastic Agents, Phytogenic (administration & dosage, pharmacokinetics, pharmacology)
• Cell Line, Tumor
• Drug Carriers (chemistry, metabolism)
• Drug Delivery Systems
• Fatty Acids (chemistry, metabolism)
• Humans
• Integrin alphaVbeta3 (metabolism)
• Melanoma (drug therapy, metabolism)
• Micelles
• Oligopeptides (chemistry, metabolism)
• Paclitaxel (administration & dosage, pharmacokinetics, pharmacology)
• Surface-Active Agents (chemistry, metabolism)