Optimizing a Lipid-Nanocarrier for Efficient Loading and Delivery of - - PowerPoint PPT Presentation

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Mar 10, 2023 241 likes •380 views

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

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Victoria Steffes, PhD Candidate Safinya Group

Optimizing a Lipid-Nanocarrier for Efficient Loading and Delivery of a Hydrophobic Drug: Paclitaxel

Lauren Galvin, MRL RET Program Participant

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Paclitaxol

✤ Standard of Care: ✤ Solubilized in Cremophor &

ethanol

✤ Causes hypersensitivity

reactions

✤ Reduces potential

therapeutic index

Halts cell division via microtubule stabilization

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EndoTAG

✤ 3 Component system: ✤ DOTAP, DOPC & Paclitaxol ✤ Unilamellar Structure ✤ Passive Targeting , EPR and

electrostatic favorability

✤ No systematic understanding of

factors controlling:

✤ Drug loading ✤ Intracellular drug delivery

Stage III Trials

DOTAP DOPC

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Proposed Methods to Improve Drug Loading and Delivery

✤ Unalamellar vs Multilamellar ✤ Achieve more drug/particle

Oupicky et al. J. Cont. Rel. (2013) Majzoub et al. Biomaterials (2014)

EndoTAG proposed condensed structure

hydrophobic drug nucleic acid lipid bilayer

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Cell Uptake and Drug Delivery

Endosomal uptake: endocytosis, fusion

r endosomal rupture

EPR: enhanced permeation and retention effect through “leaky” tumor vasculature

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Results: Inhibitory Concentration at 50%: value at 50nM to serve as control for future experiments

IC50 EndoTAG

Preliminary step to compare to for studies

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Inquiry

Will more flexible membranes (achieved by adding cosurfactant) effectively accommodate more drug?

cosurfactant vitamin E hexanol geraniol

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Proposed Methods to Improve Drug Loading and Delivery

✤ Identify lipids and cosurfactants that stabilize more

drug within membrane

saturation
methylation
charge
valence
tail length
other additive types

vitamin E hexanol geraniol

Koudelka and Turanek. J. Control. Release. 2012; 163: 322-334

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Results: Hexanol nor Geraniol are not toxic at the proposed concentrations. Both surfactants seem comparable at this time.

IC50 of Cosurfactants

Hexanol and Geraniol

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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!

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Zetasizer

✤ One of the methods we use to characterize the physical

properties of our liposomes.

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Next Step

Cell Viability Assay Comparing:

✤ Consurfactants Geraniol vs Hexanol ✤ Unilamellar vs Multilamellar ✤ Control With and Without Cosurfactant

(with and without drug)

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Thank You

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