Pharmaceutical Sciences
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12503/21636
Browse
Browsing Pharmaceutical Sciences by Author "Jameson, Jeffrey"
Now showing 1 - 2 of 2
- Results Per Page
- Sort Options
Item Effect of Cholesterol Content on Surface Properties of Doxil-Mimicking Liposomes(2019-03-05) Garrett, Meredith; Mishra, Ina; Kastellorizios, Michail; Jameson, JeffreyPurpose: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.Item Investigating Effects of Pegylation of the Surface Tension of Liposomes used in the Treatment of Breast Cancer(2019-03-05) Jameson, Jeffrey; Mishra, Ina; Kastellorizios, Michail; Garrett, MeredithPurpose: 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.