Carbon nanoparticles suspension injection for the delivery of doxorubicin: Comparable efficacy and reduced toxicity

Mater Sci Eng C Mater Biol Appl. 2018 Nov 1:92:416-423. doi: 10.1016/j.msec.2018.07.012. Epub 2018 Jul 4.

Abstract

Drug delivery systems for doxorubicin (DOX) have attracted tremendous interest nowadays for the improved efficacy and/or reduced toxicity. Due to the aromatic structures and hydrophobic domains, carbon nanoparticle suspension injection (CNSI), a clinical applied reagent for lymph node mapping, strongly adsorbs DOX and holds great potential in cancer therapy. Herein, we evaluated the therapeutic effects of CNSI-DOX to establish its delivery applications for cancer drugs. CNSI adsorbed DOX from solution quickly after the mixing, and the release of DOX from CNSI followed a pH-dependent way. CNSI-DOX and free DOX had nearly identical inhibitive effects on cancer cells, while the vehicle CNSI was nontoxic. CNSI-DOX largely prolonged the life span of ascites tumor bearing mice after the intraperitoneally injection and the ascites weights showed significant decreases. CNSI-DOX also inhibited the growth of subcutaneous xenografts following the same administration route. The therapeutic efficacy of CNSI-DOX was similar to that of free DOX in ascites tumor model, but slightly lower in subcutaneous xenografts model. The advantage of using CNSI was majorly reflected by the reduced toxicity of DOX according to the bodyweight changes, serum biochemical indicators and histopathological observations. The LD50 (median lethal dose) value of CNSI-DOX was 43.8 mg/kg bodyweight, nearly three times of that of free DOX (15.2 mg/kg bodyweight). Our results suggested that CNSI might be used for DOX delivery through "off label" use to benefit the patients immediately.

Keywords: Carbon nanoparticles suspension injection; Doxorubicin; Drug delivery; Toxicity; Tumor.

MeSH terms

  • Carbon* / chemistry
  • Carbon* / pharmacokinetics
  • Carbon* / pharmacology
  • Doxorubicin* / chemistry
  • Doxorubicin* / pharmacokinetics
  • Doxorubicin* / pharmacology
  • Drug Delivery Systems / methods*
  • HeLa Cells
  • Humans
  • MCF-7 Cells
  • Nanoparticles* / chemistry
  • Nanoparticles* / therapeutic use
  • Neoplasms, Experimental / drug therapy*
  • Neoplasms, Experimental / metabolism
  • Neoplasms, Experimental / pathology

Substances

  • Carbon
  • Doxorubicin