Encapsulation of N-Diazeniumdiolates within Liposomes for Enhanced Nitric Oxide Donor Stability and Delivery

Mol Pharm. 2015 Oct 5;12(10):3569-74. doi: 10.1021/acs.molpharmaceut.5b00248. Epub 2015 Aug 28.

Abstract

The rapid decomposition of nitric oxide (NO) donors in aqueous environments remains a limitation for applications requiring extended NO release. Herein, we report the synthesis of dipalmitoylphosphatidylcholine-based liposomes capable of extended NO release using low molecular weight NO donors and a reverse-phase evaporation technique. The encapsulation of the NO donors within the liposomes enabled both prolonged NO release and enhanced storage compared to free NO donors alone. The NO-releasing liposomes also demonstrated enhanced efficacy against human pancreatic cancer cells. These NO-release vehicles represent attractive anticancer therapeutics due to their potential to store the majority of their NO payload until reaching cancerous tissue at which time the lower pH inherent to such environments will trigger an avalanche of NO.

Keywords: cancer; controlled release; drug delivery; liposome; nitric oxide.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Azo Compounds / administration & dosage*
  • Azo Compounds / therapeutic use
  • Cell Line, Tumor
  • Drug Compounding / methods*
  • Drug Delivery Systems / methods
  • Drug Stability
  • Humans
  • Liposomes / administration & dosage
  • Liposomes / therapeutic use*
  • Nitric Oxide Donors / administration & dosage*
  • Pancreatic Neoplasms / drug therapy

Substances

  • Azo Compounds
  • Liposomes
  • Nitric Oxide Donors
  • diazeniumdiolate