Increased bioavailability of rifampicin from stimuli-responsive smart nano carrier

ACS Appl Mater Interfaces. 2014 Oct 8;6(19):16895-902. doi: 10.1021/am504402b. Epub 2014 Sep 24.

Abstract

Stimuli responsive polymeric nanocarrier (RCOP-2) functionalized with frontline antituberculosis drug (Rifampicin) is demonstrated for sustained release. Bioavailability of Rifampicin is taken care of by conjugating this drug through a acylhydrazine linker to the polymeric backbone. The poly(ethylene glycol) structural motif is introduced in the copolymer architecture for water solubility. Releasing retinal along with Rifampicin is hypothesized to reduce the risk of side effects due to Rifampicin. The self-assembly of RCOP-2, due to the amphiphilicity present in the copolymer, is explored in detail. The pH responsiveness of RCOP-2 is demonstrated in mild acidic environment as well as in cell lines. The 4T cell line, due to its acidic nature, shows time-dependent cellular internalization. On the basis of the results, our unique design is expected to provide an increased bioavalaibility of Rifampicin with reduced side effects. From the flow cytometry results on A549 cell lines, it is clear that the newly designed copolymer RCOP-2 can internalize efficiently and serve as an effective Rifampicin delivery system.

Keywords: ROMP; Rifampicin; drug delivery; retinal; stimuli responsive.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Availability
  • Cell Death / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Chromatography, Gel
  • Drug Carriers / chemistry*
  • Flow Cytometry
  • Fluorescein-5-isothiocyanate / metabolism
  • Humans
  • Hydrogen-Ion Concentration
  • Kinetics
  • Nanoparticles / chemistry*
  • Polyethylene Glycols / chemical synthesis
  • Polyethylene Glycols / chemistry
  • Polymerization / drug effects
  • Retinaldehyde / chemical synthesis
  • Retinaldehyde / chemistry
  • Rifampin / pharmacology*
  • Spectrophotometry, Ultraviolet

Substances

  • Drug Carriers
  • Polyethylene Glycols
  • Fluorescein-5-isothiocyanate
  • Retinaldehyde
  • Rifampin