A thermoresponsive chitosan-based in situ gel formulation incorporated with 5-FU loaded nanoerythrosomes for fibrosarcoma local chemotherapy

Int J Biol Macromol. 2024 Oct;278(Pt 4):134781. doi: 10.1016/j.ijbiomac.2024.134781. Epub 2024 Aug 14.

Abstract

Local administration of drugs at tumor sites over an extended period of time shows potential as a promising approach for cancer treatment. In the present study, the temperature-induced phase transition of chitosan and poloxamer 407 is used to construct an injectable hydrogel encapsulating 5-FU-loaded nanoerythrosome (5-FU-NER-gel). The 5-FU-NERs were found to be spherical, measuring approximately 115 ± 20 nm in diameter and having a surface potential of -7.06 ± 0.4. The drug loading efficiency was approximately 40 %. In situ gel formation took place within 15 s when the gel was exposed to body temperature or subcutaneous injection. A sustained release profile was observed at pH 7.4 and 6.8, with a total 5-FU release of 76.57 ± 4.4 and 98.07 ± 6.31 in 24 h, respectively. MTT, Live/dead, and migration assays confirmed the cytocompatibility of the drug carrier and its effectiveness as a chemotherapeutic formulation. After in vivo antitumor assessment in a subcutaneous autograft model, it was demonstrated that tumor growth inhibition in 14 days was 90 %. Therefore, the obtained injectable chitosan-based hydrogel containing 5-FU-loaded nanoerythrosomes illustrated promising potential as a candidate for local and enhanced delivery of chemotherapeutics at the tumor site.

Keywords: 5-FU; Fibrosarcoma; In situ gel; Local cancer chemotherapy; Nanoerythrosome; Solid tumor.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Chitosan* / chemistry
  • Drug Carriers* / chemistry
  • Drug Liberation
  • Fibrosarcoma* / drug therapy
  • Fibrosarcoma* / pathology
  • Fluorouracil* / administration & dosage
  • Fluorouracil* / chemistry
  • Fluorouracil* / pharmacology
  • Humans
  • Hydrogels / chemistry
  • Mice
  • Nanoparticles / chemistry
  • Poloxamer / chemistry
  • Temperature

Substances

  • Chitosan
  • Fluorouracil
  • Drug Carriers
  • Hydrogels
  • Poloxamer