Effect of Composition and Size on Surface Properties of Anti-Cancer Nanoparticles
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<sup>...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/17/13417 |
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| author | Ina Mishra Meredith Garrett Stephen Curry Jeffrey Jameson Michail Kastellorizios |
| author_facet | Ina Mishra Meredith Garrett Stephen Curry Jeffrey Jameson Michail Kastellorizios |
| author_sort | Ina Mishra |
| collection | DOAJ |
| description | 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<sup>®</sup> (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<sup>®</sup> 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<sup>®</sup> 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. |
| first_indexed | 2024-03-10T23:21:21Z |
| format | Article |
| id | doaj.art-5483be7787c84a1ca1ce27753a192aac |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T23:21:21Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-5483be7787c84a1ca1ce27753a192aac2023-11-19T08:16:59ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-08-0124171341710.3390/ijms241713417Effect of Composition and Size on Surface Properties of Anti-Cancer NanoparticlesIna Mishra0Meredith Garrett1Stephen Curry2Jeffrey Jameson3Michail Kastellorizios4Department of Pharmaceutical Sciences, University of North Texas System College of Pharmacy, University of North Texas Health Science Center, Fort Worth, TX 76107, USADepartment of Pharmaceutical Sciences, University of North Texas System College of Pharmacy, University of North Texas Health Science Center, Fort Worth, TX 76107, USADepartment of Pharmaceutical Sciences, University of North Texas System College of Pharmacy, University of North Texas Health Science Center, Fort Worth, TX 76107, USADepartment of Pharmaceutical Sciences, University of North Texas System College of Pharmacy, University of North Texas Health Science Center, Fort Worth, TX 76107, USADepartment of Pharmaceutical Sciences, University of North Texas System College of Pharmacy, University of North Texas Health Science Center, Fort Worth, TX 76107, USALiposomal 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<sup>®</sup> (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<sup>®</sup> 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<sup>®</sup> 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.https://www.mdpi.com/1422-0067/24/17/13417interfacial tensionliposomesnanoparticlesclinical translationDoxil<sup>®</sup> |
| spellingShingle | Ina Mishra Meredith Garrett Stephen Curry Jeffrey Jameson Michail Kastellorizios Effect of Composition and Size on Surface Properties of Anti-Cancer Nanoparticles International Journal of Molecular Sciences interfacial tension liposomes nanoparticles clinical translation Doxil<sup>®</sup> |
| title | Effect of Composition and Size on Surface Properties of Anti-Cancer Nanoparticles |
| title_full | Effect of Composition and Size on Surface Properties of Anti-Cancer Nanoparticles |
| title_fullStr | Effect of Composition and Size on Surface Properties of Anti-Cancer Nanoparticles |
| title_full_unstemmed | Effect of Composition and Size on Surface Properties of Anti-Cancer Nanoparticles |
| title_short | Effect of Composition and Size on Surface Properties of Anti-Cancer Nanoparticles |
| title_sort | effect of composition and size on surface properties of anti cancer nanoparticles |
| topic | interfacial tension liposomes nanoparticles clinical translation Doxil<sup>®</sup> |
| url | https://www.mdpi.com/1422-0067/24/17/13417 |
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