Development and modeling of arsenic-trioxide-loaded thermosensitive liposomes for anticancer drug delivery

Nicolas D. Winter, Ryan K J Murphy, Thomas V. O'Halloran, George C Schatz

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

In this article, a novel delivery system for the anticancer drug, arsenic trioxide (ATO), is characterized. The release of ATO from DPPC liposomes with MPPC lysolipid incorporated into the bilayer was measured. Upon heating the liposomes to 37°C, there was a 15-25% release over 24 hours. The ATO release from the DPPC and DPPC:MPPC (5%) systems leveled off after 10 hours at 37°C, whereas the DPPC:MPPC (10%) liposomes continue to release ATO over the 24-hour time span. Upon heating the liposomes rapidly to 42°C, the release rate was substantially increased. The systems containing lysolipids exhibited a very rapid release of a significant amount of arsenic in the first hour. In the first hour, the DPPC:MPPC (5%) liposomes released 40% of the arsenic and the DPPC:MPPC (10%) liposomes released 55% of the arsenic. Arsenic release from pure DPPC liposomes was comparable at 37 and 42°C, indicating that the presence of a lysolipid is necessary for a significant enhancement of the release rate. A coarse-grained molecular dynamics (CGMD) model was used to investigate the enhanced permeability of lysolipid-incorporated liposomes and lipid bilayers. The CG liposomes did not form a gel phase when cooled due to the high curvature; however, permeability was still significantly lower below the liquid-to-gel phase-transition temperature. Simulations of flat DPPC:MPPC bilayers revealed that a peak in the permeability did coincide with the phase transition from the gel to LC state when the lysolipid, MPPC, was present. No pores were observed in the simulations, so it is unlikely this was the permeability-enhancing mechanism.

Original languageEnglish
Pages (from-to)106-115
Number of pages10
JournalJournal of Liposome Research
Volume21
Issue number2
DOIs
Publication statusPublished - Jun 2011

Fingerprint

Liposomes
Arsenic
Pharmaceutical Preparations
Permeability
Gels
Phase Transition
Heating
arsenic trioxide
Molecular Models
Transition Temperature
Lipid Bilayers
Molecular Dynamics Simulation
Drug Delivery Systems
1-myristoyl-2-palmitoyl-sn-glycero-3-phosphocholine

Keywords

  • cancer chemotherapy
  • drug release
  • molecular dynamics
  • Nanotechnology

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Development and modeling of arsenic-trioxide-loaded thermosensitive liposomes for anticancer drug delivery. / Winter, Nicolas D.; Murphy, Ryan K J; O'Halloran, Thomas V.; Schatz, George C.

In: Journal of Liposome Research, Vol. 21, No. 2, 06.2011, p. 106-115.

Research output: Contribution to journalArticle

Winter, Nicolas D. ; Murphy, Ryan K J ; O'Halloran, Thomas V. ; Schatz, George C. / Development and modeling of arsenic-trioxide-loaded thermosensitive liposomes for anticancer drug delivery. In: Journal of Liposome Research. 2011 ; Vol. 21, No. 2. pp. 106-115.
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