Publications -- Michail Kastellorizios

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This collection is limited to articles published under the terms of a creative commons license or other open access publishing agreement since 2016. It is not intended as a complete list of the author's works.


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    Novel Method to Obtain Contact Angles of Tumor Biopsies
    (American Chemical Society, 2023-08-07) Rincon, Julio; Kastellorizios, Michail
    Characterizing the strength of a solid-liquid interface can be done by depositing a single drop of liquid on a planar solid surface and measuring the angle of the formed semicircle, called the contact angle. The contact angle of pure water is indicative of a surface's hydrophobicity and is a useful metric in biomedical applications such as tissue scaffolding and drug/tissue interactions. However, the roughness and inhomogeneity of most biological surfaces make obtaining accurate contact angles of such materials challenging. Here, we developed an instrument and methodology to obtain contact angles of tissue sections. Breast cancer tumor and nearby healthy tissue sections were used as the model biological surface. The custom instrument was built on existing equipment by improving drop dispensing accuracy in the nanoliter range, an XYZ stage, additional side view cameras, and microscope-based sample visualization. The method takes into account the inherent surface inhomogeneity and topology of tissue and the required method of illumination for contact angle acquisition. As such, the system uses an inverted microscope with a high sensitivity camera, an XYZ stage for accurate droplet placement on tissue, and multiple cameras to obtain contact angles around the entire perimeter of the drop. We tested the system with breast cancer biopsies and adjacent normal tissue from 75 patients and report here a trend of tumor exhibiting higher water contact angles, and thus higher hydrophobicity, compared to their respective normal adjacent tissue. The system described here can be used to characterize any type of biological tissue, which can be sectioned, with any liquid including water or solutions with dissolved or suspended therapeutic molecules and particles.
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    Effect of Composition and Size on Surface Properties of Anti-Cancer Nanoparticles
    (MDPI, 2023-09-09) Mishra, Ina; Garrett, Meredith; Curry, Stephen; Jameson, Jeffrey; Kastellorizios, Michail
    Liposomal formulations offer significant advantages as anticancer drug carriers for targeted drug delivery; however, due to their complexity, clinical translation has been challenging. In addition, liposomal product manufacturing has been interrupted in the past, as was the case for Doxil((R)) (doxorubicin hydrochloride liposome injection). Here, interfacial tension (IFT) measurements were investigated as a potential physicochemical characterization tool to aid in liposomal product characterization during development and manufacturing. A pendant drop method using an optical tensiometer was used to measure the interfacial tension of various analogues of Doxil((R)) liposomal suspensions in air and in dodecane. The effect of liposome concentration, formulation (PEG and cholesterol content), presence of encapsulated drug, as well as average particle size was analyzed. It was observed that Doxil((R)) analog liposomes demonstrate surfactant-like behavior with a sigmoidal-shape interfacial tension vs. concentration curve. This behavior was heavily dependent on PEG content, with a complete loss of surfactant-like behavior when PEG was removed from the formulation. In addition to interfacial tension, three data analyses were identified as able to distinguish between formulations with variations in PEG, cholesterol, and particle size: (i) polar and non-polar contribution to interfacial tension, (ii) liposomal concentration at which the polar and non-polar components were equal, and (iii) rate of interfacial tension decay after droplet formation, which is indicative of how quickly liposomes migrate from the bulk of the solution to the surface. We demonstrate for the first time that interfacial tension can be used to detect certain liposomal formulation changes, such as PEG content, encapsulated drug presence, and size variability, and may make a useful addition to physicochemical characterization during development and manufacturing of liposomal products.