title: Fatty acid-RGD peptide amphiphile micelles as potential paclitaxel delivery carriers to α(v)β₃ integrin overexpressing tumors.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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: Department of Pharmaceutics & Medicinal Chemistry, Thomas. J. Long School of Pharmacy & Health Sciences, University of the Pacific, Stockton, California, USA.
authors: Narashima Murthy
authors: NM
authors: Javali
authors: April
authors: A
authors: Raj
authors: Poonam
authors: P
authors: Saraf
authors: Xiaoling
authors: X
authors: Li
authors: Bhaskara
authors: B
authors: Jasti
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism; D016503:Drug Delivery Systems; D005227:Fatty Acids / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D008545:Melanoma / Q000188:drug therapy / Q000378:metabolism; D008823:Micelles; D009842:Oligopeptides / Q000737:chemistry* / Q000378:metabolism; D017239:Paclitaxel / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D013501:Surface-Active Agents / Q000737:chemistry / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D005227:Fatty Acids; D039302:Integrin alphaVbeta3; D008823:Micelles; D009842:Oligopeptides; D013501:Surface-Active Agents; C047981:arginyl-glycyl-aspartic acid; D017239:Paclitaxel