title: In Vitro and In Vivo Efficacy of Self-Assembling RGD Peptide Amphiphiles for Targeted Delivery of Paclitaxel.
abstract: OBJECTIVE
  The objective of this work was to compare the efficacy of self-assembling cyclic and linear RGD peptide amphiphiles as carriers for delivering paclitaxel to αvβ3 integrin overexpressing tumors.
  
  
  METHODS
  Linear (C18-ADA5-RGD) and cyclic (C18-ADA5-cRGDfK) peptide amphiphiles were synthesized and characterized for CMC, aggregation number and micelle stability using fluorescence spectroscopy methods. Size and morphology of micelles was studied using TEM. Fluorescence polarization and confocal microscopy assays were established to compare binding and internalization of micelles. The targeting efficacy was studied in A2058 cells using cytotoxicity assay as well as in vivo in melanoma xenograft mouse model.
  
  
  RESULTS
  The linear and cyclic RGD amphiphiles exhibited CMC of 25 and 8 μM, respectively, formed nano-sized spherical micelles and showed competitive binding to αvβ3 integrin protein. FITC-loaded RGD micelles rapidly internalized into A2058 melanoma cells. Paclitaxel-loaded RGD micelles exhibited higher cytotoxicity compared with free drug in A2058 cells in vitro as well as in vivo.
  
  
  CONCLUSIONS
  Cyclic RGD micelles exhibited better targeting efficacy but were less effective compared to linear RGD micelles as drug delivery vehicle due to lower drug solubilization capacity and lesser kinetic stability. Results from the study proved the effectiveness of self-assembling low molecular weight RGD amphiphiles as carriers for targeted delivery of paclitaxel.
authors.affiliation: Department of Pharmaceutics and Medicinal Chemistry, Thomas J. Long School of Pharmacy and Health Sciences, University of the Pacific, Stockton, USA.
authors.forename: Poonam
authors.initials: P
authors.lastname: Saraf
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Li
authors.forename: Lisa
authors.initials: L
authors.lastname: Wrischnik
authors.forename: Bhaskara
authors.initials: B
authors.lastname: Jasti
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods; D016650:Fluorescein-5-isothiocyanate / Q000737:chemistry; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D008545:Melanoma / Q000188:drug therapy; D051379:Mice; D008823:Micelles; D018613:Microscopy, Confocal / Q000379:methods; D009842:Oligopeptides / Q000737:chemistry*; D017239:Paclitaxel / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D004337:Drug Carriers; D039302:Integrin alphaVbeta3; D008823:Micelles; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid; D016650:Fluorescein-5-isothiocyanate; D017239:Paclitaxel