Designed inorganic porous nanovector with controlled release and MRI features for safe administration of doxorubicin

Int J Pharm. 2019 Jan 10:554:327-336. doi: 10.1016/j.ijpharm.2018.10.074. Epub 2018 Nov 2.

Abstract

The inability of traditional chemotherapeutics to reach cancer tissue reduces the treatment efficacy and leads to adverse effects. A multifunctional nanovector was developed consisting of porous silicon, superparamagnetic iron oxide, calcium carbonate, doxorubicin and polyethylene glycol. The particles integrate magnetic properties with the capacity to retain drug molecules inside the pore matrix at neutral pH to facilitate drug delivery to tumor tissues. The MRI applicability and pH controlled drug release were examined in vitro together with in-depth material characterization. The in vivo biodistribution and compound safety were verified using A549 lung cancer bearing mice before proceeding to therapeutic experiments using CT26 cancer implanted mice. Loading doxorubicin into the porous nanoparticle negated the adverse side effects encountered after intravenous administration highlighting the particles' excellent biocompatibility. Furthermore, the multifunctional nanovector induced 77% tumor reduction after intratumoral injection. The anti-tumor effect was comparable with that of free doxorubicin but with significantly alleviated unwanted effects. These results demonstrate that the developed porous silicon-based nanoparticles represent promising multifunctional drug delivery vectors for cancer monitoring and therapy.

Keywords: Biocompatibility; Cancer therapy; Nanoparticle; Porous silicon; Safety; Theranostics.

Publication types

  • Comparative Study

MeSH terms

  • A549 Cells
  • Animals
  • Antibiotics, Antineoplastic / administration & dosage*
  • Antibiotics, Antineoplastic / pharmacokinetics
  • Antibiotics, Antineoplastic / toxicity
  • Chemistry, Pharmaceutical / methods
  • Colonic Neoplasms / drug therapy
  • Colonic Neoplasms / pathology
  • Delayed-Action Preparations
  • Doxorubicin / administration & dosage*
  • Doxorubicin / pharmacokinetics
  • Doxorubicin / toxicity
  • Drug Delivery Systems*
  • Drug Liberation
  • Excipients / chemistry*
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / pathology
  • Magnetic Resonance Imaging
  • Male
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Nanoparticles
  • Porosity
  • Silicon / chemistry
  • Tissue Distribution

Substances

  • Antibiotics, Antineoplastic
  • Delayed-Action Preparations
  • Excipients
  • Doxorubicin
  • Silicon