An Alternative Method To Quantify Surface Properties of Anti-Cancer Drugs




Curry, Stephen
Mishra, Ina
Kastellorizios, Michail


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Purpose Physicochemical properties such as size and size distribution affect liposome formulations’ physical stability and accumulation in the target tissue. The FDA’s “Liposome Drug Products, Guidance for Industry”, 2018 emphasized size and size-distribution as “critical quality attributes”, however, it does not mention the criteria for an acceptable polydispersity index (PDI), currently measured using size-scattering technique. A monodisperse, homogenous size distribution population (PDI≤0.3) is desired. In this work, we measured surface tension of two different size distributions of liposome populations, with lipid composition similar to clinically approved anticancer formulation DOXIL, as a method to quantify liposome surface properties. This work establishes a building block in our long-term goal of obtaining insight into and facilitating the translation of nanoparticles from animal to human studies by offering additional preclinical characterization techniques based on surface properties of nanoparticles. Method Liposome formulations A and B, consisting of hydrogenated (Soy) phosphatidyl choline, cholesterol, and DSPE-PEG (7.64:5.17:1 molar ratio) were formulated in-house using thin film hydration method and probe sonication. Average particle size (PS) and PDI was obtained using dynamic light scattering (Mobius122, Wyatt Technology). The two formulations were fabricated with small differences in probe sonication process, yielding slightly different PDIs but the same average PS. The formulations were tested at two different lipid concentrations: 1mg/ml and 0.1mg/ml. Surface energy measurements were obtained on all four using pendant drop method, reported as mean with standard error (n=3) against the PDI. Results Average PS for A and B was similar (92.9±1.6 nm, 90.3±0.4 nm respectively), with PDIs 0.1±0.02 and 0.04±0.02 respectively. As expected, the surface tension was significantly decreased with concentration. PDI was found to significantly affect the total surface tension at higher concentration tested (1mg/ml) while it did not play a role at the lower concentration tested (0.1mg/ml). Interestingly, this trend was reversed when the surface tension was broken into its polar and dispersive components. Conclusions This work confirmed that small PDI changes, arising from slight variations in fabrication/manufacturing process, can translate into measurable changes in surface properties that can be obtained more rapidly and with higher accuracy than conventional DLS-based sizing techniques.