Targeted delivery of anticancer agents via a dual function nanocarrier with an interfacial drug-interactive motif

Biomacromolecules. 2014 Nov 10;15(11):4326-35. doi: 10.1021/bm501339j. Epub 2014 Oct 28.

Abstract

We have developed a dual-function drug carrier, polyethylene glycol (PEG)-derivatized farnesylthiosalicylate (FTS). Here we report that incorporation of a drug-interactive motif (Fmoc) into PEG5k-FTS2 led to further improvement in both drug loading capacity and formulation stability. Doxorubicin (DOX) formulated in PEG5k-Fmoc-FTS2 showed sustained release kinetics slower than those of DOX loaded in PEG5k-FTS2. The maximum tolerated dose of DOX- or paclitaxel (PTX)-loaded PEG5k-Fmoc-FTS2 was significantly higher than that of the free drug. Pharmacokinetics and biodistribution studies showed that DOX/PEG5k-Fmoc-FTS2 mixed micelles were able to retain DOX in the bloodstream for a significant amount of time and efficiently deliver the drug to tumor sites. More importantly, drug (DOX or PTX)-loaded PEG5k-Fmoc-FTS2 led to superior antitumor activity over other treatments including drugs formulated in PEG5k-FTS2 in breast cancer and prostate cancer models. Our improved dual function carrier with a built-in drug-interactive motif represents a simple and effective system for targeted delivery of anticancer agents.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / metabolism
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / metabolism
  • Drug Carriers / administration & dosage*
  • Drug Carriers / metabolism
  • Drug Delivery Systems / methods*
  • Female
  • Humans
  • MCF-7 Cells
  • Mice
  • Mice, Inbred BALB C
  • Nanocapsules / administration & dosage*
  • Polyethylene Glycols / administration & dosage
  • Polyethylene Glycols / metabolism
  • Xenograft Model Antitumor Assays / methods

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Nanocapsules
  • Polyethylene Glycols