Poly(3-hydroxybutyrate-CO-3-hydroxyvalerate) PHBHV biocompatible nanocarriers for 5-FU delivery targeting colorectal cancer

Drug Deliv. 2019 Dec;26(1):318-327. doi: 10.1080/10717544.2019.1582729.

Abstract

Aiming to address the issue of poor bioavailability of most anti-tumor medicines against colorectal cancer, we developed a targeted anticancer nanocarrier using biocarriers able to both bind and easily release their load in a controlled manner. Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) carriers were obtained via the emulsification-diffusion method, loaded with 5-fluorouracil and then characterized in terms of particle morphology and size (SEM, DLS), drug uptake and release. The cytotoxic potential of the 5-fluorouracil-loaded polymer nanocarriers on human adenocarcinoma cells (HT-29 cell line) was investigated. The in vitro studies clearly demonstrated that while the nanocarriers themselves slightly alter HT-29 cell viability, when loaded with 5-fluorouracil they significantly decrease cell viability, suggesting that the polymer itself exhibits low cytotoxicity and the drug-loaded carrier acts in an efficient manner to kill HT-29 human adenocarcinoma cells.

Keywords: 5-FU; HT-29; Nanocarrier; anticancer efficacy; colorectal cancer; polyhydroxyalkanoate.

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / pathology
  • Antimetabolites, Antineoplastic / administration & dosage
  • Antimetabolites, Antineoplastic / pharmacology
  • Biological Availability
  • Cell Survival / drug effects
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / pathology
  • Drug Carriers / chemistry
  • Drug Delivery Systems
  • Drug Liberation
  • Fluorouracil / administration & dosage*
  • Fluorouracil / pharmacology
  • HT29 Cells
  • Humans
  • Microscopy, Electron, Scanning
  • Nanoparticles
  • Particle Size
  • Polyesters / chemistry*
  • Polymers / chemistry

Substances

  • Antimetabolites, Antineoplastic
  • Drug Carriers
  • Polyesters
  • Polymers
  • poly(3-hydroxybutyrate)-co-(3-hydroxyvalerate)
  • Fluorouracil

Grants and funding

Part of this work was supported by a grant of the Romanian National Authority for Scientific Research and Innovation, CNCS – UEFISCDI, project number PN-II-RU-TE-2014-4-1272, 3/01.10.2015 and Unitatea Executiva pentru Finantarea Invatamantului Superior, a Cercetarii, Dezvoltarii si Inovarii.