Multifunctional Nanocarriers for Drug Delivery ApplicationsPrinciple Investigator: Joerg Lahann, Department of Chemical EngineeirngProject Sponsors: Sahar Rahmani, Graduate Student, Jason Gregory, Graduate StudentStudent Researchers: Melissa Cadena, Luke Roggenkamp

AbstractNano-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 MicroscopeThe 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.

NanoSightThe 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.  

ConclusionsThe 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 52. pH of 7

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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