The influence of dipalmitoyl phosphatidylserine on phase behaviour of and cellular response to lyotropic liquid crystalline dispersions.
Lyotropic liquid crystalline nanoparticles (cubosomes) have the potential to act as amphiphilic scaffolds for the presentation of lipids and subsequent application in, for example, bioseparations and therapeutic delivery. In this work we have formulated lyotropic liquid crystalline systems based on the synthetic amphiphile 1,2,3-trihydroxy-3,7,11,15-tetramethylhexadecane (phytantriol) and containing the lipid dipalmitoyl phosphatidylserine (DPPS). We have prepared a range of DPPS-containing phytantriol cubosome formulations and characterized them using Small Angle X-ray Scattering and Cryo-transmission electron microscopy. These techniques show that increased DPPS content induces marked changes in lyotropic liquid crystalline phase behaviour, characterized by changes in crystallographic dimensions and increases in vesicle content. Furthermore, in vitro cell culture studies indicate that these changes correlate with lipid/surfactant cellular uptake and cytotoxicity. A model cell membrane based on a surface supported phospholipid bilayer was used to gain insights into cubosome-bilayer interactions using Quartz Crystal Microgravimetry. The data show that mass uptake at the supported bilayer increased with DPPS content. We propose that the cytotoxicity of the DPPS-containing dispersions results from changes in lipid/surfactant phase behaviour and the preferential attachment and fusion of vesicles at the cell membrane.
Shen
Hsin-Hui
HH
CSIRO Molecular and Health Technologies, Clayton South, Victoria 3169, Australia. hsin-hui.shen@csiro.au
Crowston
Jonathan G
JG
Huber
Florian
F
Saubern
Simon
S
McLean
Keith M
KM
Hartley
Patrick G
PG
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005233:Fatty Alcohols / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D050866:Liquid Crystals / Q000737:chemistry*; D051379:Mice; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000648:ultrastructure; D010316:Particle Size; D044367:Phase Transition / Q000187:drug effects*; D010718:Phosphatidylserines / Q000494:pharmacology*; D058525:Quartz Crystal Microbalance Techniques; D053838:Scattering, Small Angle; D055672:Static Electricity; D013501:Surface-Active Agents / Q000494:pharmacology*; D017356:Synchrotrons; D053835:Unilamellar Liposomes / Q000737:chemistry; D014961:X-Ray Diffraction
D005233:Fatty Alcohols; D010718:Phosphatidylserines; D013501:Surface-Active Agents; D053835:Unilamellar Liposomes; C038694:dipalmitoylphosphatidylserine; C508873:3,7,11,15-tetramethyl-1,2,3-hexadecanetriol