Cyclic RGD-conjugated Pluronic® blending system for active, targeted drug delivery

Int J Nanomedicine. 2018 Aug 10:13:4627-4639. doi: 10.2147/IJN.S171794. eCollection 2018.

Abstract

Background: Blending micellar systems of different types of polymers has been proposed as an efficient approach for tailor-made drug formulations. The lamellar structure of hydrophobic polymers may provide a high drug loading capacity, and hydrophilic polymers may provide good colloidal stability.

Methods: In this study, the anticancer model drug docetaxel was loaded onto a nanosized blending micellar system with two pluronics (L121/F127). To achieve increased antitumor activity, the cyclic arginine-glycine-aspartic acid tripeptide (cRGD) as an active tumor targeting ligand was conjugated to the blending system.

Results: The docetaxel-loaded Pluronic blending system exhibited a higher drug loading capacity than that of F127 and showed high colloidal stability with a spherical structure. cRGD conjugates demonstrated enhanced drug cellular uptake and anticancer activity against αvβ3 integrin-overexpressing U87MG cancer cells. In vivo animal imaging also revealed that the prepared cRGD-conjugated nanoparticles effectively accumulated at the targeted tumor site through an active and passive targeting strategy.

Conclusion: Accordingly, the prepared nanosized system shows potential as a tailor-made, active targeting, nanomedicinal platform for anticancer therapy. We believe that this novel nanoplatform will provide insights for advancement of tumor therapy.

Keywords: Pluronic L121/F127; active targeting; blending micellar system; cyclic RGD; docetaxel; nanomedicine.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Drug Compounding
  • Drug Delivery Systems / methods*
  • Endocytosis / drug effects
  • Female
  • Humans
  • Integrin alphaVbeta3 / metabolism
  • Mice, Inbred BALB C
  • Mice, Nude
  • Micelles
  • Nanoparticles / chemistry
  • Peptides, Cyclic / chemistry*
  • Poloxamer / chemistry*

Substances

  • Antineoplastic Agents
  • Integrin alphaVbeta3
  • Micelles
  • Peptides, Cyclic
  • cyclic arginine-glycine-aspartic acid peptide
  • Poloxamer