Size Measurement of Targeted Nanoparticle Delivery Systems

Natalia Farkas¹, John A. Dagata¹, Kathleen F. Pirollo² and Esther H. Chang²

¹National Institute of Standards & Technology, Gaithersburg MD 20899 USA

²Department of Oncology, Georgetown University Medical Center, 2700 Reservoir Road, Washington DC 20017 USA

The mean size and size distribution of a targeted nanoparticle delivery system (NDS) strongly influences the intrinsic stability and functionality of this molecular complex, affects its performance as a systemic drug delivery platform, and ultimately determines its efficacy towards early detection and treatment of cancer. Since its components undergo significant reorganization during multiple stages of self-assembly, it is essential to monitor size and stability of the complex throughout NDS formulation. Furthermore, reproducible and quantitative size measurement of individual entities, not only average properties of the entire population, is needed to assure potency and manufacturability of a specific formulation prior to entering clinical trials. Scanning probe microscopy (SPM) is capable of providing both high-resolution imaging of intact NDS immobilized on a substrate under fluid conditions and statistically meaningful, number-weighted averaged data for the complex. This presentation describes robust sample preparation methods and statistical image analysis of targeted liposome-based NDS with encapsulated therapeutic and diagnostic agents [1]. We present detailed examples of how variations in NDS formulation impact the size and stability of complexes with various payloads. These measurements are then compared with mean particle size distributions obtained by dynamic light scattering (DLS) [2]. SPM-based size distribution measurement technique in combination with DLS offers quantitative means of assessing size and stability, optimizing of formulation during drug development, and quality control during manufacturing of NDS.

[1] J. A. Dagata, N. Farkas, C. L. Dennis, R. D. Shull, V. A. Hackley, C. Yang, K. F. Pirollo, and E. H. Chang, Physical characterization methods for iron-oxide contrast agents encapsulated within a targeted liposome-based delivery system, Nanotechnology, 19, 305101, (2008)

[2] N. Farkas, J. A. Dagata, C. Yang, K. F. Pirollo, and E. H. Chang, Combined scanning probe and light scattering characterization of multi-stage self-assembly of targeted liposome-based delivery systems, manuscript in preparation

CATEGORY: Biotechnology

Mentors Name: John A. Dagata

Division, Laboratory: PED, MEL

Room, Building Mail stop: E103/217, MS 8212

Tel: 301 975 3597

Fax: 301 869 0822

Email: natalia.farkas@nist.gov

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