{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:07:01Z","timestamp":1791288421175,"version":"4.3.0"},"reference-count":35,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T00:00:00Z","timestamp":1693353600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Pharmaceutical Research and Manufacturers of America","award":["2019"],"award-info":[{"award-number":["2019"]}]},{"name":"Pharmaceutical Research and Manufacturers of America","award":["2U54MD006882-06"],"award-info":[{"award-number":["2U54MD006882-06"]}]},{"DOI":"10.13039\/100006545","name":"National Institute on Minority Health and Health Disparities","doi-asserted-by":"publisher","award":["2019"],"award-info":[{"award-number":["2019"]}],"id":[{"id":"10.13039\/100006545","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006545","name":"National Institute on Minority Health and Health Disparities","doi-asserted-by":"publisher","award":["2U54MD006882-06"],"award-info":[{"award-number":["2U54MD006882-06"]}],"id":[{"id":"10.13039\/100006545","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u00ae (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\u00ae 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\u00ae 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.<\/jats:p>","DOI":"10.3390\/ijms241713417","type":"journal-article","created":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T09:44:46Z","timestamp":1693388686000},"page":"13417","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Effect of Composition and Size on Surface Properties of Anti-Cancer Nanoparticles"],"prefix":"10.3390","volume":"24","author":[{"given":"Ina","family":"Mishra","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of North Texas System College of Pharmacy, University of North Texas Health Science Center, Fort Worth, TX 76107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0452-8294","authenticated-orcid":false,"given":"Meredith","family":"Garrett","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of North Texas System College of Pharmacy, University of North Texas Health Science Center, Fort Worth, TX 76107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Curry","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of North Texas System College of Pharmacy, University of North Texas Health Science Center, Fort Worth, TX 76107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Jameson","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of North Texas System College of Pharmacy, University of North Texas Health Science Center, Fort Worth, TX 76107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michail","family":"Kastellorizios","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of North Texas System College of Pharmacy, University of North Texas Health Science Center, Fort Worth, TX 76107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Xu, M., Han, X., Xiong, H., Gao, Y., Xu, B., Zhu, G., and Li, J. (2023). Cancer Nanomedicine: Emerging Strategies and Therapeutic Potentials. Molecules, 28.","DOI":"10.3390\/molecules28135145"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"236","DOI":"10.7150\/ntno.77564","article-title":"Natural and synthetic nanovectors for cancer therapy","volume":"7","author":"Eftekhari","year":"2023","journal-title":"Nanotheranostics"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Longo, J.P.F., and Muehlmann, L.A. (2023). Application of Nanomedicine in Immunotherapy: Recent Advances and Prospects. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15071910"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1016\/j.jconrel.2023.02.015","article-title":"Vaccine-like nanomedicine for cancer immunotherapy","volume":"355","author":"Yi","year":"2023","journal-title":"J. Control. Release"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2445","DOI":"10.1021\/acs.accounts.9b00228","article-title":"Survey of Clinical Translation of Cancer Nanomedicines-Lessons Learned from Successes and Failures","volume":"52","author":"He","year":"2019","journal-title":"Acc. Chem. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e10246","DOI":"10.1002\/btm2.10246","article-title":"Nanoparticles in the clinic: An update post COVID-19 vaccines","volume":"6","author":"Anselmo","year":"2021","journal-title":"Bioeng. Transl. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.addr.2020.07.002","article-title":"Liposomes: Advancements and innovation in the manufacturing process","volume":"154\u2013155","author":"Shah","year":"2020","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"120093","DOI":"10.1016\/j.ijpharm.2020.120093","article-title":"A supercritical fluid technology for liposome production and comparison with the film hydration method","volume":"592","author":"Penoy","year":"2021","journal-title":"Int. J. Pharm."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.nano.2019.02.019","article-title":"Liposomes produced by microfluidics and extrusion: A comparison for scale-up purposes","volume":"18","author":"Shah","year":"2019","journal-title":"Nanomedicine"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"120807","DOI":"10.1016\/j.ijpharm.2021.120807","article-title":"PLGA-based nanomedicines manufacturing: Technologies overview and challenges in industrial scale-up","volume":"605","author":"Operti","year":"2021","journal-title":"Int. J. Pharm."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1177\/1078155215594415","article-title":"Is it equivalent? Evaluation of the clinical activity of single agent Lipodox(R) compared to single agent Doxil(R) in ovarian cancer treatment","volume":"22","author":"Smith","year":"2016","journal-title":"J. Oncol. Pharm. Pract."},{"key":"ref_12","unstructured":"(2018). Liposome Drug Products, Chemistry, Manufacturing, and Controls; Human Pharmacokinetics and Bioavailability; and Labeling Documentation, Food and Drug Administration, CDER. Guidance for Industry."},{"key":"ref_13","unstructured":"(2022). Drug Products, Including Biological Products, that Contain Nanomaterials, Guidance for Industry, Food and Drug Administration, CDER."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/978-3-319-72041-8_11","article-title":"Nanoparticle-Protein Interaction: The Significance and Role of Protein Corona","volume":"1048","author":"Ahsan","year":"2018","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S0076-6879(05)91004-5","article-title":"The liposomal formulation of doxorubicin","volume":"391","author":"Abraham","year":"2005","journal-title":"Methods Enzymol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"113851","DOI":"10.1016\/j.addr.2021.113851","article-title":"Liposome composition in drug delivery design, synthesis, characterization, and clinical application","volume":"176","author":"Large","year":"2021","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5783","DOI":"10.2147\/IJN.S254808","article-title":"Protein-Nanoparticle Interaction: Corona Formation and Conformational Changes in Proteins on Nanoparticles","volume":"15","author":"Park","year":"2020","journal-title":"Int. J. Nanomed."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1146\/annurev-bioeng-071811-150124","article-title":"The effect of nanoparticle size, shape, and surface chemistry on biological systems","volume":"14","author":"Albanese","year":"2012","journal-title":"Annu. Rev. Biomed. Eng."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.addr.2015.09.012","article-title":"PEGylation as a strategy for improving nanoparticle-based drug and gene delivery","volume":"99","author":"Suk","year":"2016","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.jconrel.2012.03.020","article-title":"Doxil(R)\u2014The first FDA-approved nano-drug: Lessons learned","volume":"160","author":"Barenholz","year":"2012","journal-title":"J. Control. Release"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"6948","DOI":"10.1039\/C5NR09158F","article-title":"Time-evolution of in vivo protein corona onto blood-circulating PEGylated liposomal doxorubicin (DOXIL) nanoparticles","volume":"8","author":"Hadjidemetriou","year":"2016","journal-title":"Nanoscale"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1002\/bab.1291","article-title":"Comprehensive analysis of PEGylated liposome-associated proteins relating to the accelerated blood clearance phenomenon by combination with shotgun analysis and conventional methods","volume":"62","author":"Kawanishi","year":"2015","journal-title":"Biotechnol. Appl. Biochem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1166\/jbn.2020.2958","article-title":"Role of Physicochemical Properties of Protein in Modulating the Nanoparticle-Bio Interface","volume":"16","author":"Dhar","year":"2020","journal-title":"J. Biomed. Nanotechnol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Simon, J., Kuhn, G., Fichter, M., Gehring, S., Landfester, K., and Mailander, V. (2021). Unraveling the In Vivo Protein Corona. Cells, 10.","DOI":"10.3390\/cells10010132"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2525","DOI":"10.1021\/ja107583h","article-title":"Physical-chemical aspects of protein corona: Relevance to in vitro and in vivo biological impacts of nanoparticles","volume":"133","author":"Monopoli","year":"2011","journal-title":"J. Am. Chem. Soc."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2088","DOI":"10.1021\/acsnano.1c07687","article-title":"Opsonin-Deficient Nucleoproteic Corona Endows UnPEGylated Liposomes with Stealth Properties In Vivo","volume":"16","author":"Giulimondi","year":"2022","journal-title":"ACS Nano"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"9599","DOI":"10.1039\/C8SM02129E","article-title":"The effect of particle wettability on the stick-slip motion of the contact line","volume":"14","author":"Kim","year":"2018","journal-title":"Soft Matter"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1140\/epje\/i2017-11541-5","article-title":"Effects of interplay of nanoparticles, surfactants and base fluid on the surface tension of nanocolloids","volume":"40","author":"Harikrishnan","year":"2017","journal-title":"Eur. Phys. J. E"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"111270","DOI":"10.1016\/j.msec.2020.111270","article-title":"The influence of shape and charge on protein corona composition in common gold nanostructures","volume":"117","author":"Bewersdorff","year":"2020","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4091","DOI":"10.2147\/IJN.S249622","article-title":"Size-Dependent Interactions of Lipid-Coated Gold Nanoparticles: Developing a Better Mechanistic Understanding through Model Cell Membranes and In Vivo Toxicity","volume":"15","author":"Engstrom","year":"2020","journal-title":"Int. J. Nanomed."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"218","DOI":"10.18433\/J32P40","article-title":"Impact of surface tension in pharmaceutical sciences","volume":"12","author":"Jouyban","year":"2009","journal-title":"J. Pharm. Pharm. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.ejpb.2019.05.006","article-title":"Effect of nanoparticle size and PEGylation on the protein corona of PLGA nanoparticles","volume":"141","author":"Partikel","year":"2019","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Varlamova, E.G., Gudkov, S.V., Plotnikov, E.Y., and Turovsky, E.A. (2022). Size-Dependent Cytoprotective Effects of Selenium Nanoparticles during Oxygen-Glucose Deprivation in Brain Cortical Cells. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23137464"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4916","DOI":"10.1021\/acsbiomaterials.0c00743","article-title":"Effect of Nanoparticle Composition, Size, Shape, and Stiffness on Penetration Across the Blood-Brain Barrier","volume":"6","author":"Brown","year":"2020","journal-title":"ACS Biomater. Sci. Eng."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"673","DOI":"10.2217\/nnm.16.5","article-title":"The effect of nanoparticle size on in vivo pharmacokinetics and cellular interaction","volume":"11","author":"Hoshyar","year":"2016","journal-title":"Nanomedicine"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/17\/13417\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:42:28Z","timestamp":1760128948000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/17\/13417"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,30]]},"references-count":35,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["ijms241713417"],"URL":"https:\/\/doi.org\/10.3390\/ijms241713417","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,30]]}}}