Oral Presentation 2014 International Biophysics Congress

Engineering lipid nanoparticles for multimodal delivery of hydrophobic pharmaceutical drugs (#117)

Peter J. Judge 1 , Juan F. Bada 2 , Daniel J. Yin 1 , Horst Vogel 2 , Anthony Watts 1
  1. Oxford University, Oxford, UK
  2. EPFL, Lausanne, Switzerland

An estimated 40% of commercially available drugs, and around 90% of those in development have poor solubility in aqueous environments.1 Novel lipid-based formulations (typically 100 nm in diameter) have been developed to assist in delivery to patient tissues, however encapsulation of the active compounds generally leads to a decrease in efficacy and may produce additional side effects. Lipodisqs are coin-shaped, polymer-stabilised nanoparticles, typically 10 nm in diameter, which are currently used to deliver skin toning agents in cosmetic products.2 They may be prepared without the use of detergent and have been used to solubilise and characterise integral membrane proteins, including a 7TM photoreceptor.3 Lipodisqs are evaluated as drug delivery agents for Doxorubicin, a potent anti-tumour drug, which is commercially available as the PEGylated liposomal formulation DoxilTM. Delivery of the drug to intracellular compartments of HeLa cells is followed by confocal microscopy and IC50 measurements show that, unlike in the case of encapsulated systems, there is no decrease in in vitro efficacy over the water-solubilised form of the drug. The lipid content of the disqs may be modified to allow stimulation of drug release by changes in temperature or pH, or exposure to UV light, and to allow targeting to tumour cells.

[1] Loftsson and Brewster (2010) J. Pharm. Pharmacol. 62(11) 1607-21

[2] Orwick et al. (2012) Angew. Chem. Int. Ed. 51(19) 4653-7

[3] Orwick-Rydmark et al. (2012) Nano Lett. 12(9) 4687-92