Hetty Nie, Bioengineering Department Lipid Coated Biodegradable Nanoparticles for Drug Delivery

Summer Discovery Grant, 2012

Objective: Traditional treatment methods of many diseases suffer from the usage of systemic approaches, which relies on diseased tissue, such as tumors, using more nutrients and therefore accumulating a higher and toxic dosage of drugs than healthy tissues. However, these treatments have severe side effects and low efficacy. Recent nanotechnology-based methods such as nano-scale drug carriers hold a great promise to address the drawbacks of using traditional systemic treatments, with increased efficacy and better specificity. The goal of this project was to combine two facets of nanoscale drug carriers, biodegradable polymeric nanoparticles and nanoscale lipid vesicles, to create lipid-coated biodegradable nanoparticles for drug delivery that overcomes multiple shortcomings of traditional approaches. Approach: To fabricate biodegradable poly-lactic-(co)glycolic acid (PLGA) nanoparticles, I established two different methods based on literature: an oil in water double emulsion technique; and a fluidics based system. In the former method, PLGA was dissolved in an organic solvent and then added to a surfactant while vortexing to create an emulsion. This emulsion was then sonicated to increase the uniformity and homogeneity of the nanoparticles. Finally, the sonicated solution was added to another aqueous solution and the solvent was evaporated. Conversely in the latter, the solution of PLGA in an organic solvent was injected into a tubing in which a surfactant solution was running at a constant flow rate. The shear stress of the aqueous surfactant solution on the incoming PLGA solution resulted in particles formation. In both methods, the resultant particles were centrifuged multiple times to remove excess surfactant. To characterize these particles, I used scanning electron microscopy and dynamic light scattering, and found that the fluidics-based system formed particles with a more uniform size distribution compared to the emulsion technique. Additionally, using dynamic light scattering, I was able to find the correlation between the particle size and the concentration of PLGA in the organic phase, or the applied flow rate. Hence, by manipulating these fabrication parameters I was able to optimize the particle fabrication procedure. To create the lipid coating, I prepared lipid vesicles of a combination of three different lipids and a small amount of fluorescent lipids for the visualization purposes. These vesicles were then sonicated with the nanoparticles to coat the nanoparticles in lipids. The resulting solution was centrifuged to remove excess lipids. I compared coated particles to uncoated ones using dynamic light scattering and confirmed the formation of a lipid coating. Additionally, I visualized coated particles using fluorescence microscopy which also confirmed a lipid coating. Finally, I included a drug, curcumin, with is applied in treatment of Alzheimers disease, into the organic solution of PLGA during the nanoparticle fabrication process. Curcumin was successfully included, but the new particles have not yet been characterized. This aim will be completed in the upcoming semester. Conclusion and Future Work: In summary, I have established a procedure for fabrication of lipid coated PLGA nanoparticles and characterized the resulting particles. The fabricated lipid coated drug-encapsulated nanoparticles are uniform, biocompatible, and biodegradable, and therefore suitable for future applications in targeted drug delivery. Continued work for this project includes not only the addition of targeting molecules in the lipid membrane, but also the use of other polymers to decrease the degradation rate. Furthermore, the uptake of the particles by cells will be characterized as well as any additional interactions of the particles with cells.