PHYSICAL CHARACTERIZATION OF LIPOSOME-BASED TARGETED NANOPARTICLE DELIVERY SYSTEMS WITH ENCAPSULATED MRI CONTRAST AGENTS

Natalia Farkas, John A. Dagata, Cindi L. Dennis, Robert D. Shull and Vincent A. Hackley

National Institute of Standards and Technology, Gaithersburg , MD 20899

Chengli Yang, Kathleen F. Pirollo and Esther H. Chang

Georgetown University Medical Center, 2700 Reservoir Road, Washington DC 20017

Liposome-based nanoparticle delivery systems (NDS) with encapsulated super-paramagnetic iron-oxide (SPIO) contrast agent are promising candidates for early detection of cancer due to their ability of target-specific magnetic resonance imaging (MRI) contrast enhancement. MRI performance of these SPIO NDS depends on the elementary particle size, aggregation and magnetization of the contrast agent. Physical characterization of NDS is therefore essential during formulation and manufacturing of NDS as size and size distribution determine functionality, stability, efficacy and ultimately potential to be considered for clinical trials. Reproducible and quantitative size measurements of all components are critical in every step of the assembly process. Since NDS and SPIO colloidal solutions are often highly aggregated size characterization can be challenging. We demonstrate that scanning probe microscopy (SPM) is a powerful tool both for high-resolution imaging and for particle size analysis yielding number-weighted size distributions. In particular, we present results for intact NDS nonspecifically immobilized by tuning the surface potential of the substrate for SPM characterization in a fluid imaging environment. Quantitative measurements are obtained from the SPM imaging data with attention paid to tip calibration, statistically meaningful data collection and pixelation of the data. By combining SPM results with superconducting quantum interference device (SQUID) magnetometry, dynamic light scattering (DLS), and electron microscopy measurements, we observe particle size dependence of the magnet moment of iron-oxide nanoparticles at the 10-nm length scale and the stability of liposome-based NDS at the 100-nm length scale. Our approach to quantitative size distribution measurements of nanoparticles and assessment of structure-function relationship of individual, multi-component nanoscale entities by integrated SPM-based characterization techniques and sample preparation methods provides repeatable and reproducible measurement methods and standards of biomaterials.

Author Information

Name:                                    Natalia Farkas

Mentor’s name:                   John A. Dagata

Division:                                Precision Engineering Division

Laboratory:                          Manufacturing Engineering Laboratory

Room/Building:                   E103/217

Mail Stop:                             MS 8212

Telephone #:                        301 975 3597

Fax #:                                    301 869 0822

Email:                                    natalia.farkas@nist.gov

Sigma Xi:                              Non-member

Category:                              Biotechnology