Assessment of doxorubicin delivery devices based on tailored bare polycaprolactone against glioblastoma

Int J Pharm. 2019 Mar 10;558:110-119. doi: 10.1016/j.ijpharm.2018.12.079. Epub 2019 Jan 9.

Abstract

Bare polycaprolactones with controlled molar mass and dispersity were employed to manufacture biodegradable devices, which were applied for doxorubicin delivery in glioblastoma. Micro- and nanoscale devices were prepared by emulsion formation or by a combination of precipitation and hydrolysis. The carriers were characterized by scanning electron microscopy, dynamic light scattering techniques, thermogravimetric analysis and differential scanning calorimetry. The encapsulation parameters and drug-release profiles are discussed in order to evaluate the influence of different fundamental parameters, such as molar mass and dispersity value, pH, morphology or crystallinity, on the efficiency of the doxorubicin delivery systems. The ability of doxorubicin-loaded micro- and nanoscale devices to induce cellular toxicity in glioblastoma cells was also explored. A cell viability assay against C6 cells of doxorubicin-loaded nanocarriers showed higher cytotoxicity than doxorubicin-loaded microcarriers. In addition, doxorubicin-loaded nanocarriers also showed good antitumor profile in human tumoral cells and improved the security profile in relation to free doxorubicin in non-tumoral cells. Consistent with the assessment study described in this manuscript, the results provide a proof of concept for the suitability of the approach, based on bare polycaprolactone, to local controlled-sustained release of doxorubicin for the treatment of glioblastoma.

Keywords: Doxorubicin delivery devices; Glioblastoma; Polycaprolactone; Polymeric nanocarriers; Polymeric porous microspheres.

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / administration & dosage*
  • Antibiotics, Antineoplastic / chemistry
  • Cell Survival / drug effects
  • Cells, Cultured
  • Central Nervous System Neoplasms / drug therapy*
  • Doxorubicin / administration & dosage*
  • Doxorubicin / chemistry
  • Drug Delivery Systems*
  • Female
  • Glioblastoma / drug therapy*
  • Humans
  • Macrophages, Peritoneal / drug effects
  • Mice, Inbred C57BL
  • Nanoparticles / administration & dosage
  • Nanoparticles / chemistry
  • Polyesters / administration & dosage*
  • Polyesters / chemistry
  • Rats, Sprague-Dawley

Substances

  • Antibiotics, Antineoplastic
  • Polyesters
  • polycaprolactone
  • Doxorubicin