Investigating Effects of Pegylation of the Surface Tension of Liposomes used in the Treatment of Breast Cancer

Purpose: In recent years there have been many advancements in nanomedicine as potential delivery systems for the treatment of various types of cancer. Two formulations on the market, Doxil® and Myocet®, are made of doxorubicin-loaded liposomes. One them, Doxil® has the hydrophilic polymer polyethylene glycol (PEG) immobilized on its surface, while the other (Myocet®) doesn’t. PEG has been shown to improve liposome circulation in the blood by disguising them from the immune system, creating a ‘stealth’ delivery system for drugs. However, it is unknown whether the PEG changes the way liposomes may interact within the tumor. Here, we fabricated liposomes that mimic Doxil® and Myocet® and measured their surface tension, as surface tension is a driving force behind the interfacial interactions between liposomes and tumor extracellular matrix. Materials and Methods: Two formulations of liposomes (Doxil® and Myocet®) were fabricated using thin film hydration for liposome formation and membrane extrusion for liposome downsizing to nanometer levels. A thin film of each formulation was made and then hydrated with phosphate buffered saline. Extrusion was performed using a 50nm membrane bringing final liposome size of each formulation to approximately 100nm. The Doxil® formulation contained hydrogenated soybean phosphatidylcholine (HSPC), cholesterol and PEG, while the Myocet® contained only HSPC and cholesterol. The two formulations underwent a series of dilutions, and the surface tension of each concentration was calculated using the twin capillary rise method. A custom 3D printed stand coupled with a well plate was used to secure the capillaries while allowing small volumes of the formulations to be used. Results: Data collected showed a significant decrease in surface tension when PEG is removed from the surface of the liposomes. This effect was consistent across all concentrations when compared to the original formulation. Conclusions: Our results show that PEG causes a drastic change in how liposomes interact with surfaces. Further, we demonstrated that this effect is greatly affected by small changes in liposome concentration. The reduction in surface tension observed in Myocet® versus Doxil® may be the reason behind Doxil’s sustained success in the clinic compared to Myocet®. Future studies will focus on quantifying interfacial tension between these liposome formulations and breast cancer biopsies in order to potentially explain their different clinical performance.