Examining Functionalized Vesosomes as an Improved Drug Delivery - - PowerPoint PPT Presentation

Examining Functionalized Vesosomes as an Improved Drug Delivery Vehicle

Jason Schmidt Jason Schmidt

Allan Hancock College Allan Hancock College

Bio Bio-

• Engineering major

Engineering major INSET Mentor: Ben Wong INSET Mentor: Ben Wong Faculty Advisor: Joe Zasadzinski Faculty Advisor: Joe Zasadzinski UCSB Department of Chemical Engineering UCSB Department of Chemical Engineering

Funding By:

• Program of Excellence in Nanotechnology

(PEN)

• National Institutes of Health (NIH)
• National Science Foundation (NSF)

Zasadzinski Group

What Is A Vesosome? What Is A Vesosome?

A vesicle is a tiny phospholipid bi-layer “bubble”

Vesosome, diameter ~ 1um Vesicle, diameter ~ 50 nm

A vesosome is a comparably larger vesicle that encapsulates many smaller vesicles

Zasadzinski Group

The Potential to Greatly Increase the The Potential to Greatly Increase the Efficiency of Drug Therapies Efficiency of Drug Therapies

Increase in drug retention in vivo Multi-compartment structure may

allow loading of drug “cocktails”

Potential for drug targeting,

further reducing side-effects

Reduction in amount of drug(s) necessary for therapy Reduction of side effects / damage to healthy tissues Increase in time-release control Enhanced resistance to immune

system

Summer Research Goals Summer Research Goals

Dilution Filtration Injection

Begin In Vivo Experimentation & Analysis

Vesosome Production Vesosome Production

Heating Purification Formation of Sheets

Add EtOH Wash

Formation of Vesicles

Freeze/ Thaw

“Onions” Vesicles Vesicles Interdigitation Sheets

Vesosomes In Buffer Vesosomes In Buffer

Confocal Microscope Green Channel Confocal Microscope Red Channel Confocal Microscope Red+Green Channels

Vesosomes In Buffer Vesosomes In Buffer

Cryo Transmission Electron Microscope Images

Successful Encapsulation Unlikely Encapsulation TEM Image TEM Image

Confocal Microscope Red Channel Intensity Image, Inverted Confocal Microscope Red Channel Intensity Image

Vesosomes In Vivo Vesosomes In Vivo

Aggregations Vesosomes

0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 0.05 0.5 3 5 24

Time From Start (Hrs) Adjusted Vesosomal Fluorescence (a.u.) 20 40 60 80 100 120 140 160 5 10 15 20 25

Time From Start (Hrs) Avg # of Vesosomes Observed

Avg #<1um Avg #>1um Total Avg #

Average Circulation Time Average Circulation Time

• f Vesosomes In Vivo
• f Vesosomes In Vivo
• Significant difference in half-life of single vs. aggregate

vesosomes Results:

• Overall half-life ~ 2hrs, which is shorter than expected
• Vesosomes are aggregating in vivo

Zasadzinski Group

Continuing Work Continuing Work

• Continuing In Vivo Experiments
• Quantification of Functionalization
• Encapsulation of Multiple Different Internal Components
• Incorporation of Channel Proteins Into External Bi-layer

1 2 3 4 5 6

• Refine Functionalization; Control Aggregation

Acknowledgements Acknowledgements

The Joseph Zasadzinski Molecular Engineering Group

Ben Wong, Siggie Steltenkamp, Prajna Dhar, Ian Shieh, Patrick Seelheim, Patrick Stenger, Htet Khant

Internships in Nanosystems, Science, Engineering, and Technology (INSET) The Erkki Ruoslahti Group

David Peters