1. Multifunctional Nanocarriers for Drug Delivery Applications
Principle Investigator: Joerg Lahann, Department of Chemical Engineeirng
Project Sponsors: Sahar Rahmani, Graduate Student, Jason Gregory, Graduate Student
Student Researchers: Melissa Cadena, Luke Roggenkamp
Abstract
Nano-scale drug delivery systems are essential in the delivery of
medication for diseases such as cancer. Our research lab, Lahann Research
Group, is working to create a targeted drug delivery system.
Chemotherapy, a current treatment for cancer is not targeted to the tumor
and affects all organs in the body. An ideal drug delivery system should be
nano-scaled and contain surface modifications to travel throughout the
body and preferentially distribute within the tumor.
In order to create the multifunctional drug delivery systems, we have:
fabricated particles through Electrohydrodynamic (EHD) co-jetting,
modified the surface for targeting and circulation, and characterized the
nanoparticles. EHD co-jetting is the process of applying an electric field to
a polymer solution to create multi-compartmental nanoparticles with
specific properties. The nanoparticles created from the co-jetting process
are collected using a grounded metal substrate. The results have yielded
stable nanoparticles that have been surface modified to include ligands to
increase circulation. To characterize these nanoparticles, equipment such
as the Scanning Electron Microscope (SEM) and Nanosight are used to
track individual particle size and particle concentration in a solution. These
steps are essential in determining how the size and concentration of the
nanoparticles are affected in different mediums, particularly blood, before
the particles are used in animal studies. The analysis of these results is
vital in order to create a drug delivery system that is safe, targets a specific
location in the body, and can be tested before animal studies are carried
out. In the future, we will be testing the particles made through the EHD
co-jetting process in hopes of developing an effective and versatile drug
delivery system.
Electrohydrodynamic Co-Jetting (EHD Co-jetting)
EHD Co-jetting is a process to create particles of desired size,
shape, and functionality. The jetting station includes a syringe
pump, cage, power supply, and grounded plate. First, a specific
ratio polymer solution is measured and loaded into a syringe. The
syringe is then placed into the pump and the flow rate is set. A
grounded metal plate is set beneath the pump to create an electric
field. Voltage is applied once a droplet of solution is formed on
the needles. The voltage causes the solution to accelerate to 250
meters per second, which reduces the diameter of the jet and
forms a Taylor cone. This acceleration causes the solvent to
evaporate and rapid solidification of the particles occurs. Due to
the electric field, the particles fall to the grounded plate and are
collected for further manipulation.
Confocal and Scanning Electron Microscope
The confocal microscope and the Scanning Electron
Microscope (SEM) provide 3-D images of the particles
unobservable to the human eye. The confocal microscope
allows us to observe the biphasic nature of particles.
Fluorescent dyes can also be seen using a confocal
microscope and are used to help distinguish between
multiple phases. The SEM is used to determine the size
and morphology of particles.
NanoSight
The NanoSight is a system used to trace effective size
and concentration of particles over time. Fluorescent
dyes are used to track the particles in different
mediums such as blood. The ability to keep the
particles in their natural medium prevents damage to
the particles from purification. The NanoSight is used
to test different parameters (size, shape, surface
modifications, etc.) in the desired medium before
animal studies are conducted. The NanoSight returns
data on the concentration of particles and individual
particle size.
Conclusions
The particles we created this year have been used for a variety
of medical applications for the treatment of cancer.
• We created particles with compartmentalized cancer
therapeutics to test controlled release. These particles were
placed in solutions with varying pH to observe the effects of
pH on the degradation of the particle. The results showed
that the particles degraded faster in lower pH, which implies
the controlled release of therapeutics is possible.
• We created particles that were surface modified with
functional groups to target brain tumors. The particles were
tested in animals and yielded positive results.
• We created bi-compartmental particles with different cancer
therapeutics to be used as a method to treat breast cancer.
The purpose of this study is to create particles with a time
dependent release. This study is on-going and few definitive
results have been obtained.
Future Work
• We will continue to test the particles ability to pass through
the blood brain barrier, with particles containing
chemotherapeutic agents and biomolecules.
• We will attempt to create particles that have preferential
binding to epithelial tissue.
• We will continue with the study on the creation of particles
for a treatment for breast cancer. We are trying to show that
we can control the release of therapeutics on a time
dependent basis.
Jetting Schematic
PLGA particles with fluorescent dye
imaged under the Confocal Microscope
Acetyl Dextran Particles imaged under the SEM at
1000X after being incubated for 15 hours at:
1. pH of 5
2. pH of 7
1
2
Formation of a Taylor Cone in the
jetting process
Spherical Microparticles
imaged under the SEM
Lomustine particles imaged under the SEM at
5000X
NanoSight Batch Results