Novel injectable thermosensitive hydrogels for delivering hyaluronic acid-doxorubicin nanocomplexes to locally treat tumors

Nanomedicine (Lond). 2015;10(8):1263-74. doi: 10.2217/nnm.14.211. Epub 2014 Dec 5.

Abstract

Aim: A thermosensitive injectable hydrogel composed of nanocomplexes of doxorubicin and hyaluronic acid (HA) for the local treatment of cancer diseases was developed and characterized.

Materials & methods: It was found that the addition of a divalent metal ion of Mg (MgCl2) was required to properly form HA-doxorubicin nanocomplexes, which were mixed with Pluronic® F127 (BASF, Germany) to form thermosensitive injectable hydrogels.

Results: The DH700KMF-15 hydrogel resulted in efficient growth inhibition of C26 colon cancer cells and it selectively targeted the lymphatic system by the specific affinity of HA to the lymphatic system in vivo.

Conclusion: The optimal formulations of DH700KMF-15 can increase the therapeutic efficacy of the local treatment of cancer with the potential for lymphotropic targeting to inhibit metastasis.

Keywords: Pluronic F127; doxorubicin; hyaluronic acid; hydrogel; intratumoral.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / administration & dosage*
  • Antibiotics, Antineoplastic / pharmacokinetics
  • Antibiotics, Antineoplastic / therapeutic use
  • Cell Line, Tumor
  • Colon / drug effects
  • Colon / pathology
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / pathology
  • Delayed-Action Preparations / chemistry*
  • Doxorubicin / administration & dosage*
  • Doxorubicin / pharmacokinetics
  • Doxorubicin / therapeutic use
  • Humans
  • Hyaluronic Acid / chemistry*
  • Hydrogels / chemistry*
  • Injections
  • Lymph Nodes / drug effects
  • Lymph Nodes / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Phase Transition
  • Poloxamer / chemistry*
  • Temperature

Substances

  • Antibiotics, Antineoplastic
  • Delayed-Action Preparations
  • Hydrogels
  • Poloxamer
  • Doxorubicin
  • Hyaluronic Acid