Arginine, glycine, aspartic acid peptide-modified paclitaxel and curcumin co-loaded liposome for the treatment of lung cancer: in vitro/vivo evaluation

Int J Nanomedicine. 2018 Apr 27:13:2561-2569. doi: 10.2147/IJN.S157746. eCollection 2018.

Abstract

Purpose: In this study, a novel arginine, glycine, aspartic acid peptide (RGD)-modified paclitaxel and curcumin co-loaded liposomes were developed to evaluate their antitumor activity in vitro and in vivo.

Materials and methods: Co-loaded liposomes were prepared using the solvent evaporation method. The particles had spherical shapes under electron microscopy with sizes <130 nm.

Results: By comparison with the free drug, RGD-modified paclitaxel and curcumin co-loaded liposomes and paclitaxel and curcumin co-loaded liposomes have sustained-release properties in vitro. In vivo, there was no significant difference in pharmacokinetic parameters between the RGD-modified paclitaxel and curcumin co-loaded liposomes and paclitaxel and curcumin co-loaded liposomes. A strong green fluorescence was observed in the cytoplasmic region after incubation of RGD-modified paclitaxel and curcumin co-loaded liposomes for 2 h. RGD-modified paclitaxel and curcumin co-loaded liposomes showed a superior antiproliferative effect on A549 cells with a possible mechanism that suppressed the multidrug resistance phenomenon and exhibited a clear synergistic effect.

Conclusion: The results indicate that RGD-modified paclitaxel and curcumin co-loaded liposomes had a better antitumor effect in vivo than the non-modified LPs. These results indicate that RGD-modified co-loaded liposomes are a promising candidate for antitumor drug delivery.

Keywords: arginine; aspartic acid peptide; cell uptake; curcumin; cytotoxicity study; glycine; in vivo anti-tumor study; liposome; paclitaxel.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Cell Line, Tumor
  • Curcumin / administration & dosage
  • Curcumin / chemistry
  • Curcumin / pharmacokinetics
  • Drug Delivery Systems / methods
  • Drug Liberation
  • Female
  • Humans
  • Liposomes / administration & dosage*
  • Liposomes / chemistry
  • Lung Neoplasms / drug therapy*
  • Male
  • Mice, Inbred BALB C
  • Oligopeptides / chemistry*
  • Paclitaxel / administration & dosage
  • Paclitaxel / chemistry
  • Paclitaxel / pharmacokinetics
  • Rats, Sprague-Dawley
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents, Phytogenic
  • Liposomes
  • Oligopeptides
  • arginyl-glycyl-aspartic acid
  • Curcumin
  • Paclitaxel