Stimuli-responsive lipid nanotubes in gel formulations for the delivery of doxorubicin

Colloids Surf B Biointerfaces. 2016 Jul 1:143:406-414. doi: 10.1016/j.colsurfb.2016.03.070. Epub 2016 Mar 25.

Abstract

Lipid nanotubes (LNTs) are one of the most advantageous structures for drug delivery and targeting. LNTs formed by a specially designed molecule called AQUA (AQ-NH-(CH2)10COOH (AQ: anthraquinone group) is used for drug delivery, and doxorubicin (DOX) is the drug selected. DOX and AQUA have some similarities in their molecular structures, so a significant amount of DOX can be loaded to LNTs. The AQUA LNTs are pH responsive, and drug loading increased almost linearly by increasing the pH, reaching a maximum value (96%) at pH 9.0. In terms of drug release, lower pHs are preferred. Drug-loaded LNTs are also mixed with four different gels (chitosan, alginate, hydroxypropyl methylcellulose and polycarbophil) to use the advantages of these gels. The drug release efficiency is studied using a Franz diffusion cell in which sheep colon membranes and dialysis membranes are utilized. The amount of released DOX from the chitosan gel formulations was quite high. Sodium alginate gels had lower release and slower diffusion of DOX. The cytotoxic effect of DOX-loaded AQUA LNTs has also been determined on cell cultures. Our new lipid nanotubes are a non-toxic, effective, biodegradable, biocompatible, stable and promising system for drug delivery and can be used for colonic administration of DOX for the treatment of colorectal cancer (CRC).

Keywords: Anthraquinone; Colorectal cancer; Doxorubicin; Drug delivery; Drug loading; Lipid nanotube.

MeSH terms

  • Acrylic Resins / chemistry
  • Alginates / chemistry
  • Animals
  • Anthraquinones / chemistry*
  • Antibiotics, Antineoplastic / chemistry
  • Antibiotics, Antineoplastic / pharmacology*
  • Cell Line
  • Chitosan / chemistry
  • Colon / drug effects
  • Colon / metabolism*
  • Diffusion Chambers, Culture
  • Doxorubicin / chemistry
  • Doxorubicin / pharmacology*
  • Drug Carriers / chemistry*
  • Drug Carriers / pharmacology
  • Drug Compounding
  • Drug Liberation
  • Fibroblasts / cytology
  • Fibroblasts / drug effects
  • Glucuronic Acid / chemistry
  • Hexuronic Acids / chemistry
  • Humans
  • Hydrogen-Ion Concentration
  • Hypromellose Derivatives / chemistry
  • Kinetics
  • MCF-7 Cells
  • Membranes, Artificial
  • Mice
  • Nanotubes / chemistry*
  • Nanotubes / ultrastructure
  • Sheep

Substances

  • Acrylic Resins
  • Alginates
  • Anthraquinones
  • Antibiotics, Antineoplastic
  • Drug Carriers
  • Hexuronic Acids
  • Membranes, Artificial
  • Hypromellose Derivatives
  • Doxorubicin
  • Glucuronic Acid
  • calcium polycarbophil
  • Chitosan