Assembling of stimuli-responsive tumor targeting polypyrrole nanotubes drug carrier system for controlled release

Mater Sci Eng C Mater Biol Appl. 2018 Aug 1:89:316-327. doi: 10.1016/j.msec.2018.04.031. Epub 2018 Apr 14.

Abstract

A stimuli-responsive polypyrrole (PPy) nanotubes drug carrier system has been designed to deliver anticancer drugs to tumor cells in a targeted and controlled manner. The PPy nanotubes drug carrier was fabricated by a template method. The nanotubes surface was functionalized with cleavable acylhydrazone and disulfide bonds by attaching thiolated β-cyclodextrin (β-CD). The solubilizing poly(ethylene glycol) polymer (PEG), attached with an adamantane (Ad) entity at one end and a folate (FA) entity at the other end, was introduced onto the nanotubes surface via β-cyclodextrin-adamantane interaction. The synthesized FA-PEG-Ad-β-CD-PPy showed excellent biocompatibility and low cytotoxicity for two cell lines. Doxorubicin (Dox) loaded FA-PEG-Ad-β-CD-PPy nanotubes showed a triggered in vitro drug release behavior in the presence of acidic media and reducing agents. The folate-mediated endocytosis and intracellular release of Dox-loaded nanoparticles were confirmed by fluorescence microscopy and cell viability evaluations. In the in vitro study, Dox loaded within the nanoparticles showed enhanced selectivity for cancerous cells and reduced cytotoxicity for normal cells compared to free Dox. The PPy based targeted drug vehicle shows excellent promise for drug delivery.

Keywords: Folate; Polypyrrole nanotube; Stimuli-responsive; Targeting.

MeSH terms

  • Adamantane / chemistry
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Doxorubicin / chemistry
  • Doxorubicin / metabolism
  • Doxorubicin / pharmacology
  • Drug Carriers / chemistry*
  • Drug Liberation
  • Folic Acid / chemistry
  • HEK293 Cells
  • Humans
  • Microscopy, Electron, Scanning
  • Nanotubes / chemistry*
  • Polyethylene Glycols / chemistry
  • Polymers / chemistry*
  • Pyrroles / chemistry*
  • Spectroscopy, Fourier Transform Infrared
  • beta-Cyclodextrins / chemistry

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Polymers
  • Pyrroles
  • beta-Cyclodextrins
  • polypyrrole
  • Polyethylene Glycols
  • Doxorubicin
  • Folic Acid
  • betadex
  • Adamantane