Filomicelles from aromatic diblock copolymers increase paclitaxel-induced tumor cell death and aneuploidy compared with aliphatic copolymers

Nanomedicine (Lond). 2016 Jun;11(12):1551-69. doi: 10.2217/nnm-2016-0007. Epub 2016 May 13.

Abstract

Aim: In order to improve the delivery of aromatic drugs by micellar assemblies, and particularly by long and flexible filomicelles, aromatic groups were integrated into the hydrophobic block of a degradable diblock copolymer.

Materials & methods: Aromatic filomicelles were formed by self-directed assembly of amphiphilic diblock copolymer PEG-PBCL with suitable block ratios. Worm-like filomicelles with an aromatic core were loaded with a common chemotherapeutic, Paclitaxel, for tests of release as well as effects on cancer cell lines in vitro and in vivo.

Results: Aromatic filomicelles loaded more Paclitaxel than analogous aliphatic systems. Cell death and aneuploidy of surviving cells (which indicates toxicity) were highest for carcinoma lines treated in vitro with the new filomicelles. Initial tests in vivo also suggest more potent tumor shrinkage.

Conclusion: Flexible filomicelles with an aromatic core form an efficient drug delivery system that leads to higher cell death than previously reported systems, while inducing aneuploidy in surviving cells.

Keywords: cylinder micelle; cytokinesis; drug delivery; worm micelle.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / administration & dosage*
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Cell Death / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Drug Carriers / chemistry*
  • Humans
  • Hydrocarbons, Aromatic / chemistry
  • Hydrophobic and Hydrophilic Interactions
  • Mice, SCID
  • Micelles*
  • Neoplasms / drug therapy
  • Paclitaxel / administration & dosage*
  • Paclitaxel / pharmacology
  • Paclitaxel / therapeutic use
  • Polyethylene Glycols / chemistry*
  • Polymers / chemistry

Substances

  • Antineoplastic Agents, Phytogenic
  • Drug Carriers
  • Hydrocarbons, Aromatic
  • Micelles
  • Polymers
  • Polyethylene Glycols
  • Paclitaxel