Antitumor effect of adriamycin-encapsulated nanoparticles of poly(DL-lactide-co-glycolide)-grafted dextran

J Pharm Sci. 2009 Jun;98(6):2104-12. doi: 10.1002/jps.21588.

Abstract

In this study, we prepared adriamycin (ADR)-encapsulated core-shell type nanoparticles of a poly(DL-lactide-co-glycolide) (PLGA) grafted-dextran (DexLG) copolymer and evaluated its antitumor activity in vitro and in vivo. The particle size of ADR-encapsulated DexLG nanoparticles was around 50-200 nm and the morphology was spherical shapes at transmission electron microscopy (TEM) observation. Since reconstitution of lyophilized nanoparticles is essential to practical use in vivo, ADR-encapsulated DexLG nanoparticles were lyophilized and reconstituted them into deionized water. Although reconstitution process caused increase of particle size, drug release behavior of nanoparticles was not significantly changed before and after reconstitution process. The ADR-encapsulated DexLG nanoparticles were less cytotoxic than free ADR plus empty nanoparticles at in vitro, while empty DexLG nanoparticles did not significantly affect cell viability. Even if free ADR plus empty nanoparticles are most effective to inhibit tumor growth at tumor-induced animal model using CT-26 cells, ADR-encapsulated DexLG nanoparticles showed increased survivability of mice. These results indicated that ADR-encapsulated DexLG nanoparticles are promising vehicles for antitumor drug delivery.

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / administration & dosage*
  • Antibiotics, Antineoplastic / therapeutic use
  • Antibiotics, Antineoplastic / toxicity
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / pathology
  • Dextrans*
  • Doxorubicin / administration & dosage*
  • Doxorubicin / therapeutic use
  • Doxorubicin / toxicity
  • Drug Carriers*
  • Freeze Drying
  • Humans
  • Lactic Acid*
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles*
  • Particle Size
  • Polyglycolic Acid*
  • Polylactic Acid-Polyglycolic Acid Copolymer

Substances

  • Antibiotics, Antineoplastic
  • Dextrans
  • Drug Carriers
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Doxorubicin