Effect of Cholesterol Content on Surface Properties of Doxil-Mimicking Liposomes




Garrett, Meredith
Jameson, Jeffrey
Mishra, Ina
Kastellorizios, Michail


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Purpose:The use of nanoparticles (NPs) for drug delivery has gained a lot of attention from biomedical researchers in the last few decades. This is primarily because NPs are of an extremely small size that enables them to accumulate preferentially inside of the tumors instead of healthy tissue. The reason is unknown as to why research being done on NPs has shown promising results in animal models but does not translate successfully to the clinic. Here, we will study the effect of NPs cholesterol content on their surface tension. Cholesterol is sometimes added to NPs to increase their rigidity and stability, but we do not know if it interferes with other properties such as surface tension. We hypothesize that surface tension can be useful in enriching characterization of novel NPs and help determine which NPs to move on to clinical testing. Methods:We used Doxil®, one of the few successful NPs for cancer therapy, as reference. Doxil® consists of a drug (doxorubicin) encapsulated in nano-sized vehicles (liposomes) made of HSPC, cholesterol (CHOL), and PEG. Two formulations of NPs, HSPC:CHOL:PEG (Doxil®) and HSPC:PEG, were prepared by thin film hydration followed by membrane extrusion. We tested their surface tension at six concentrations using the twin-capillary method. A capillary stand was 3D-printed that was able to hold the capillaries stable. Results: The average change in surface tension for the six different concentrations between the two formulations did not have a noticeable change. The surface tension decreased proportionately at the same concentrations for each of the HSPC:CHOL:PEG and HSPC:PEG formulations. In addition, the same experiment was used to compare the difference in surface tension between HSPC:CHOL and phosphatidylcholine (PC), which is equivalent to HSPC. The difference between the values were also negligible. Conclusion:Based on our results, we conclude that the inclusion of cholesterol in liposomes does not alter their surface energy properties as measured by the twin capillary rise method. This may be due to the fact that cholesterol is a small molecule while PEG is a giant molecule that covers the surface of the entire liposome. Even though cholesterol does not affect surface tension, it is still pertinent for the formulation to be effective. In future studies, an additional technique will be used (pendant drop shape analysis) that gives more insight into surface tension and breaks it into its polar and non-polar components.