optimizing a lipid nanocarrier for efficient loading and
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Optimizing a Lipid-Nanocarrier for Efficient Loading and Delivery of a Hydrophobic Drug: Paclitaxel Lauren Galvin, MRL RET Program Participant Victoria Steffes, PhD Candidate Safinya Group Paclitaxol Standard of Care: Solubilized in


  1. Optimizing a Lipid-Nanocarrier for Efficient Loading and Delivery of a Hydrophobic Drug: Paclitaxel Lauren Galvin, MRL RET Program Participant Victoria Steffes, PhD Candidate Safinya Group

  2. Paclitaxol ✤ Standard of Care: ✤ Solubilized in Cremophor & ethanol ✤ Causes hypersensitivity reactions ✤ Reduces potential therapeutic index Halts cell division via microtubule stabilization

  3. EndoTAG Stage III Trials DOTAP ✤ 3 Component system: ✤ DOTAP, DOPC & Paclitaxol DOPC ✤ Unilamellar Structure ✤ Passive Targeting , EPR and electrostatic favorability ✤ No systematic understanding of factors controlling: ✤ Drug loading ✤ Intracellular drug delivery

  4. Proposed Methods to Improve Drug Loading and Delivery ✤ Unalamellar vs Multilamellar ✤ Achieve more drug/particle proposed condensed EndoTAG structure hydrophobic drug nucleic acid lipid bilayer Oupicky et al. J. Cont. Rel. (2013) Majzoub et al. Biomaterials (2014)

  5. Cell Uptake and Drug Delivery Endosomal uptake: endocytosis, fusion EPR: enhanced permeation or endosomal rupture and retention effect through “leaky” tumor vasculature

  6. IC50 EndoTAG Preliminary step to compare to for studies Results: Inhibitory Concentration at 50%: value at 50nM to serve as control for future experiments

  7. Inquiry Will more flexible membranes (achieved by adding cosurfactant) effectively accommodate more drug? cosurfactant vitamin E geraniol hexanol

  8. Proposed Methods to Improve Drug Loading and Delivery ✤ Identify lipids and cosurfactants that stabilize more drug within membrane • saturation vitamin E • methylation • charge • valence • tail length geraniol • other additive types hexanol Koudelka and Turanek. J. Control. Release . 2012; 163 : 322-334

  9. IC50 of Cosurfactants Hexanol and Geraniol Results: Hexanol nor Geraniol are not toxic at the proposed concentrations. Both surfactants seem comparable at this time.

  10. IC50: Drug and Surfactants in both Unilamellar and Multilamellar Liposomes ✤ Determine the effectiveness of liposomes with drug and surfactants, both bare (unilamellar) and with DNA (multilamellar). ✤ Currently waiting on results!

  11. Zetasizer ✤ One of the methods we use to characterize the physical properties of our liposomes.

  12. Next Step Cell Viability Assay Comparing: ✤ Consurfactants Geraniol vs Hexanol ✤ Unilamellar vs Multilamellar ✤ Control With and Without Cosurfactant (with and without drug)

  13. Thank You ✤ MRL, Research Experience for Teachers Program ✤ Frank Kinnaman, RET Coordinator ✤ Mary McGuan, Education Programs Assistant ✤ Victoria Steffes, Mentor/PhD Candidate ✤ Safinya Group

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