N,N,N-trimethyl chitosan embedded in situ Pluronic F127 hydrogel for the treatment of brain tumor

Carbohydr Polym. 2019 Jan 1;203:302-309. doi: 10.1016/j.carbpol.2018.09.065. Epub 2018 Sep 28.

Abstract

The malignant gliomas are most destructive brain tumor having low drug response. The thermosensitive hydrogel from pluronic F127 (PF127) and N,N,N-trimethyl chitosan (TMC) is developed as a drug delivery system for anticancer drug docetaxel (DTX) to the glioblastoma multiforme. The influence of TMC on morphology, physico-chemical, mechanical, and release properties of PF127 based thermosensitive hydrogel is investigated here. The hydrogels shows porous network as shown by scanning electron microscopy and TMC addition hindered close packing of PF127 layers in the gel system leaving more pores on the surface. TEM images demonstrate micelle formation by PF127-TMC with diameters of about 50 nm. MTT assay result shows that DTX loaded PF127-TMC hydrogel is more capable of killing U87MG cell than free DTX and DTX loaded PF-127. Hydrogels retain sustained release of DTX under different pH conditions more than one month. Furthermore, in vivo experiments are carried out by creating xenograft tumor model on the head of BALB/c nude mice for checking tumor suppression by PF127-TMC/DTX hydrogel. Overall, the hydrogels shows sustained release of DTX on different pH with tumor suppression suggests that it can be used for treating tumor.

Keywords: Chitosan; Docetaxel; Drug delivery; Intratumoral delivery; Thermosensitive gel.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / therapeutic use*
  • Cell Line, Tumor
  • Chitosan / chemical synthesis
  • Chitosan / chemistry*
  • Docetaxel
  • Drug Carriers / chemical synthesis
  • Drug Carriers / chemistry
  • Drug Liberation
  • Glioblastoma / drug therapy*
  • Humans
  • Hydrogels / chemical synthesis
  • Hydrogels / chemistry*
  • Hydrogen-Ion Concentration
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • Poloxamer / chemistry*
  • Taxoids / chemistry
  • Taxoids / therapeutic use*

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Hydrogels
  • N-trimethyl chitosan chloride
  • Taxoids
  • Poloxamer
  • Docetaxel
  • Chitosan