Synergistic co-delivery of doxorubicin and paclitaxel by porous PLGA microspheres for pulmonary inhalation treatment

Eur J Pharm Biopharm. 2014 Nov;88(3):1086-93. doi: 10.1016/j.ejpb.2014.09.012. Epub 2014 Oct 8.

Abstract

PLGA porous microspheres loaded with doxorubicin (DOX) and paclitaxel (PTX) were developed for in situ treatment of metastatic lung cancer. The synergistic effect of the combined drugs was investigated against B16F10 cells to obtain the optimal prescription for in vivo studies. The combination therapy showed great synergism when DOX was the majority in the combination therapy, while they showed moderate antagonism when PTX is in major. The combination of DOX and PTX at a molar ratio of 5/1 showed the best synergistic therapeutic effect in the free form. However, the drugs exhibited more synergism in the PLGA microspheres at a molar ratio of 2/1, due to the difference in drug release rate. The in vivo study verified the synergism of DOX and PTX at the optimal molar ratio. These results suggested that dual encapsulation of DOX and PTX in porous PLGA microspheres would be a promising technology for long effective lung cancer treatment.

Keywords: Doxorubicin; In situ treatment; Paclitaxel; Porous microspheres; Pulmonary inhalation; Synergistic effect.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / metabolism
  • Doxorubicin / administration & dosage*
  • Doxorubicin / metabolism
  • Drug Carriers / administration & dosage
  • Drug Carriers / metabolism
  • Drug Delivery Systems / methods*
  • Drug Synergism
  • Lactic Acid / administration & dosage*
  • Lactic Acid / metabolism
  • Lung / drug effects
  • Lung / metabolism
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Melanoma, Experimental
  • Mice
  • Mice, Inbred C57BL
  • Microspheres*
  • Paclitaxel / administration & dosage*
  • Paclitaxel / metabolism
  • Polyglycolic Acid / administration & dosage*
  • Polyglycolic Acid / metabolism
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Porosity
  • Random Allocation
  • Treatment Outcome
  • Xenograft Model Antitumor Assays / methods

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Doxorubicin
  • Paclitaxel