Liposome size analysis by dynamic/static light scattering upon size exclusion-/field flow-fractionation

Area of Science:

• Nanotechnology
• Materials Science
• Pharmaceutical Sciences

Background:

• Liposomes composed of egg phosphatidylcholine serve as prototype drug nanocarriers.
• Liposome size critically impacts drug loading, aggregation, sedimentation, pharmacokinetics, and biodistribution.
• Accurate and reproducible particle size analysis is essential for liposome-based drug delivery system design.

Purpose of the Study:

• To analyze the particle size distribution of a liposome dispersion prepared by high-pressure homogenization.
• To compare the efficacy of three distinct sub-micron particle size analysis techniques.

Main Methods:

• Photon Correlation Spectroscopy (PCS) for fixed-angle quasi-elastic laser light scattering.
• Size Exclusion Chromatographic (SEC) fractionation followed by off-line PCS analysis.
• Field-Flow Fractionation (FFF) coupled on-line with static light scattering and a refractive index detector.

Main Results:

• PCS indicated either a broad log-normal or a bimodal size distribution, dependent on data collection time.
• Fractionating techniques (SEC and FFF) revealed a dominant peak below 50 nm and a smaller, broader peak extending over 100 nm.
• Discrepancies in results were observed across the techniques, attributed to inherent limitations like detection limits and PCS overemphasis on larger particles.

Conclusions:

• All three techniques provided valuable insights into liposome size distribution, but results were not entirely congruent.
• The choice of technique and data acquisition parameters influences the interpretation of liposome particle size distribution.
• Understanding these technique-specific differences is crucial for reliable characterization of nanocarriers.