Fluorescent Rhein-Loaded Liposomes for In Vivo Biodistribution Study

<b>Objectives:</b> This work aimed to develop and investigate liposomes incorporating Rhein (Lip-Rh) into the liposomal membrane to enhance the compound’s water solubility and oral bioavailability. <b>Methods:</b> Liposomes were produced by the thin lipid film technique, with...

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Main Authors: Silviu Iulian Filipiuc, Natalia Simionescu, Gabriela Dumitrița Stanciu, Adina Coroaba, Narcisa Laura Marangoci, Leontina Elena Filipiuc, Mariana Pinteala, Cristina Mariana Uritu, Bogdan Ionel Tamba
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Language:English
Published: MDPI AG 2025-02-01
Series:Pharmaceutics
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Online Access:https://www.mdpi.com/1999-4923/17/3/307
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author Silviu Iulian Filipiuc
Natalia Simionescu
Gabriela Dumitrița Stanciu
Adina Coroaba
Narcisa Laura Marangoci
Leontina Elena Filipiuc
Mariana Pinteala
Cristina Mariana Uritu
Bogdan Ionel Tamba
author_facet Silviu Iulian Filipiuc
Natalia Simionescu
Gabriela Dumitrița Stanciu
Adina Coroaba
Narcisa Laura Marangoci
Leontina Elena Filipiuc
Mariana Pinteala
Cristina Mariana Uritu
Bogdan Ionel Tamba
author_sort Silviu Iulian Filipiuc
collection DOAJ
description <b>Objectives:</b> This work aimed to develop and investigate liposomes incorporating Rhein (Lip-Rh) into the liposomal membrane to enhance the compound’s water solubility and oral bioavailability. <b>Methods:</b> Liposomes were produced by the thin lipid film technique, with a phosphatidylcholine-to-cholesterol molar ratio of 5:1, dissolved in chloroform and methanol, and thereafter hydrated with ultrapure water and subjected to sonication. The resultant liposomes were studied from a physicochemical perspective using DLS, zeta potential, STEM, UV–Vis, and fluorescence spectroscopies, while oral bioavailability was assessed by fluorescence imaging. Additionally, cell viability assays were performed on tumour cells (MCF-7) in comparison to normal cells (HGFs). <b>Results:</b> The resultant nanoparticles exhibited relatively uniform sizes and narrow size distribution. In vivo fluorescence imaging studies performed on Wistar rats demonstrated significantly enhanced oral bioavailability for Lip-Rh, with rapid absorption into the bloodstream observed one hour after administration, in contrast to the free compound dissolved in vegetable oil. Cell viability assays demonstrated higher cytotoxicity of Lip-Rh towards MCF-7 cells compared to HGF cells, highlighting the selective therapeutic potential of the product. Moreover, we determined that the optimal dose of Rhein per kilogram of body weight, when encapsulated in liposomes, is approximately 2.5 times less than when Rhein is delivered in its unencapsulated form. <b>Conclusions:</b> Lip-Rh is a promising candidate for oncological treatments, presenting three key advantages: increased cytotoxicity towards tumour cells, protection of normal tissues, and the practicality of oral delivery. Additional investigation is required to explore its application in anticancer therapy, whether as monotherapy or as a complementary treatment.
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spelling doaj-art-7dbc4b83d24d4f4987247e07a547b1472025-08-20T02:42:24ZengMDPI AGPharmaceutics1999-49232025-02-0117330710.3390/pharmaceutics17030307Fluorescent Rhein-Loaded Liposomes for In Vivo Biodistribution StudySilviu Iulian Filipiuc0Natalia Simionescu1Gabriela Dumitrița Stanciu2Adina Coroaba3Narcisa Laura Marangoci4Leontina Elena Filipiuc5Mariana Pinteala6Cristina Mariana Uritu7Bogdan Ionel Tamba8Centre of Advanced Research in Bionanoconjugates and Biopolymers, “Petru Poni” Institute of Macromolecular Chemistry, 700487 Iasi, RomaniaCentre of Advanced Research in Bionanoconjugates and Biopolymers, “Petru Poni” Institute of Macromolecular Chemistry, 700487 Iasi, RomaniaAdvanced Center for Research and Development in Experimental Medicine “Prof. Ostin C. Mungiu”, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, RomaniaCentre of Advanced Research in Bionanoconjugates and Biopolymers, “Petru Poni” Institute of Macromolecular Chemistry, 700487 Iasi, RomaniaCentre of Advanced Research in Bionanoconjugates and Biopolymers, “Petru Poni” Institute of Macromolecular Chemistry, 700487 Iasi, RomaniaAdvanced Center for Research and Development in Experimental Medicine “Prof. Ostin C. Mungiu”, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, RomaniaCentre of Advanced Research in Bionanoconjugates and Biopolymers, “Petru Poni” Institute of Macromolecular Chemistry, 700487 Iasi, RomaniaCentre of Advanced Research in Bionanoconjugates and Biopolymers, “Petru Poni” Institute of Macromolecular Chemistry, 700487 Iasi, RomaniaAdvanced Center for Research and Development in Experimental Medicine “Prof. Ostin C. Mungiu”, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania<b>Objectives:</b> This work aimed to develop and investigate liposomes incorporating Rhein (Lip-Rh) into the liposomal membrane to enhance the compound’s water solubility and oral bioavailability. <b>Methods:</b> Liposomes were produced by the thin lipid film technique, with a phosphatidylcholine-to-cholesterol molar ratio of 5:1, dissolved in chloroform and methanol, and thereafter hydrated with ultrapure water and subjected to sonication. The resultant liposomes were studied from a physicochemical perspective using DLS, zeta potential, STEM, UV–Vis, and fluorescence spectroscopies, while oral bioavailability was assessed by fluorescence imaging. Additionally, cell viability assays were performed on tumour cells (MCF-7) in comparison to normal cells (HGFs). <b>Results:</b> The resultant nanoparticles exhibited relatively uniform sizes and narrow size distribution. In vivo fluorescence imaging studies performed on Wistar rats demonstrated significantly enhanced oral bioavailability for Lip-Rh, with rapid absorption into the bloodstream observed one hour after administration, in contrast to the free compound dissolved in vegetable oil. Cell viability assays demonstrated higher cytotoxicity of Lip-Rh towards MCF-7 cells compared to HGF cells, highlighting the selective therapeutic potential of the product. Moreover, we determined that the optimal dose of Rhein per kilogram of body weight, when encapsulated in liposomes, is approximately 2.5 times less than when Rhein is delivered in its unencapsulated form. <b>Conclusions:</b> Lip-Rh is a promising candidate for oncological treatments, presenting three key advantages: increased cytotoxicity towards tumour cells, protection of normal tissues, and the practicality of oral delivery. Additional investigation is required to explore its application in anticancer therapy, whether as monotherapy or as a complementary treatment.https://www.mdpi.com/1999-4923/17/3/307Rheinfluorescence imagingliposomal RheinRhein biodistributionRhein cytotoxicity
spellingShingle Silviu Iulian Filipiuc
Natalia Simionescu
Gabriela Dumitrița Stanciu
Adina Coroaba
Narcisa Laura Marangoci
Leontina Elena Filipiuc
Mariana Pinteala
Cristina Mariana Uritu
Bogdan Ionel Tamba
Fluorescent Rhein-Loaded Liposomes for In Vivo Biodistribution Study
Pharmaceutics
Rhein
fluorescence imaging
liposomal Rhein
Rhein biodistribution
Rhein cytotoxicity
title Fluorescent Rhein-Loaded Liposomes for In Vivo Biodistribution Study
title_full Fluorescent Rhein-Loaded Liposomes for In Vivo Biodistribution Study
title_fullStr Fluorescent Rhein-Loaded Liposomes for In Vivo Biodistribution Study
title_full_unstemmed Fluorescent Rhein-Loaded Liposomes for In Vivo Biodistribution Study
title_short Fluorescent Rhein-Loaded Liposomes for In Vivo Biodistribution Study
title_sort fluorescent rhein loaded liposomes for in vivo biodistribution study
topic Rhein
fluorescence imaging
liposomal Rhein
Rhein biodistribution
Rhein cytotoxicity
url https://www.mdpi.com/1999-4923/17/3/307
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