Liposomal and Nanostructured Lipid Nanoformulations of a Pentacyclic Triterpenoid Birch Bark Extract: Structural Characterization and In Vitro Effects on Melanoma B16-F10 and Walker 256 Tumor Cells Apoptosis

<b>Background/Objectives</b>: Pentacyclic triterpenoids are increasingly studied as anticancer agents with many advantages compared to synthetic chemotherapeutics. The aim of this study was to prepare liposomal and nanostructured lipid formulations including a standardized extract of sil...

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Main Authors: Dumitriţa Rugină, Mihai Adrian Socaciu, Madalina Nistor, Zorita Diaconeasa, Mihai Cenariu, Flaviu Alexandru Tabaran, Carmen Socaciu
Format: Article
Language:English
Published: MDPI AG 2024-12-01
Series:Pharmaceuticals
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Online Access:https://www.mdpi.com/1424-8247/17/12/1630
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author Dumitriţa Rugină
Mihai Adrian Socaciu
Madalina Nistor
Zorita Diaconeasa
Mihai Cenariu
Flaviu Alexandru Tabaran
Carmen Socaciu
author_facet Dumitriţa Rugină
Mihai Adrian Socaciu
Madalina Nistor
Zorita Diaconeasa
Mihai Cenariu
Flaviu Alexandru Tabaran
Carmen Socaciu
author_sort Dumitriţa Rugină
collection DOAJ
description <b>Background/Objectives</b>: Pentacyclic triterpenoids are increasingly studied as anticancer agents with many advantages compared to synthetic chemotherapeutics. The aim of this study was to prepare liposomal and nanostructured lipid formulations including a standardized extract of silver birch (<i>Betula pendula</i>) outer bark (TTs) and to evaluate their potential as anticancer agents in vitro, using Melanoma B16-F10 and Walker carcinoma cells. <b>Methods</b>: Appropriate solvents were selected for efficient TTs extraction, and original recipes were used to obtain Pegylated liposomes and nanolipid complexes with entrapped TTs, comparative to pure standards (betulinic acid and doxorubicin) in similar conditions. The composition, morphology, and sizes of all nanoformulations were checked by high-performance liquid chromatography/mass spectrometry, Transmission Electronic Microscopy, and Diffraction Light Scattering. The entrapment efficiency and its impact on cell viability, cell cycle arrest, and apoptosis by flow cytometry was also measured on both cancer cell lines. <b>Conclusions:</b> The standardized TTs, including betulin, lupeol, and betulinic acid, showed good stability and superior activity compared to pure betulinic acid. According to experimental data, TTs showed good entrapment in liposomal and NLC nanoformulations, both delivery systems including natural, biodegradable ingredients and enhanced bioavailability. The apoptosis and necrosis effects were more pronounced for TTs liposomal formulations in both types of cancer cells, with lower cytotoxicity compared to Doxorubicin, and can be correlated with their increased bioavailability.
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spelling doaj-art-f2a2fd74a8f04c55b2701fbfe042d6862025-08-20T02:43:45ZengMDPI AGPharmaceuticals1424-82472024-12-011712163010.3390/ph17121630Liposomal and Nanostructured Lipid Nanoformulations of a Pentacyclic Triterpenoid Birch Bark Extract: Structural Characterization and In Vitro Effects on Melanoma B16-F10 and Walker 256 Tumor Cells ApoptosisDumitriţa Rugină0Mihai Adrian Socaciu1Madalina Nistor2Zorita Diaconeasa3Mihai Cenariu4Flaviu Alexandru Tabaran5Carmen Socaciu6Faculty of Veterinary Medicine, University of Agricultural Sciences and Veterinary Medicine, 400372 Cluj-Napoca, RomaniaFaculty of Medicine, University of Medicine and Pharmacy “Iuliu Hatieganu”, 400347 Cluj-Napoca, RomaniaFaculty of Food Science and Technology, University of Agricultural Sciences and Veterinary Medicine, 400372 Cluj-Napoca, RomaniaFaculty of Food Science and Technology, University of Agricultural Sciences and Veterinary Medicine, 400372 Cluj-Napoca, RomaniaFaculty of Veterinary Medicine, University of Agricultural Sciences and Veterinary Medicine, 400372 Cluj-Napoca, RomaniaFaculty of Veterinary Medicine, University of Agricultural Sciences and Veterinary Medicine, 400372 Cluj-Napoca, RomaniaDepartment of Biotechnology, BIODIATECH—Proplanta Research Centre for Applied Biotechnology in Diagnosis and Molecular Therapy, 400478 Cluj-Napoca, Romania<b>Background/Objectives</b>: Pentacyclic triterpenoids are increasingly studied as anticancer agents with many advantages compared to synthetic chemotherapeutics. The aim of this study was to prepare liposomal and nanostructured lipid formulations including a standardized extract of silver birch (<i>Betula pendula</i>) outer bark (TTs) and to evaluate their potential as anticancer agents in vitro, using Melanoma B16-F10 and Walker carcinoma cells. <b>Methods</b>: Appropriate solvents were selected for efficient TTs extraction, and original recipes were used to obtain Pegylated liposomes and nanolipid complexes with entrapped TTs, comparative to pure standards (betulinic acid and doxorubicin) in similar conditions. The composition, morphology, and sizes of all nanoformulations were checked by high-performance liquid chromatography/mass spectrometry, Transmission Electronic Microscopy, and Diffraction Light Scattering. The entrapment efficiency and its impact on cell viability, cell cycle arrest, and apoptosis by flow cytometry was also measured on both cancer cell lines. <b>Conclusions:</b> The standardized TTs, including betulin, lupeol, and betulinic acid, showed good stability and superior activity compared to pure betulinic acid. According to experimental data, TTs showed good entrapment in liposomal and NLC nanoformulations, both delivery systems including natural, biodegradable ingredients and enhanced bioavailability. The apoptosis and necrosis effects were more pronounced for TTs liposomal formulations in both types of cancer cells, with lower cytotoxicity compared to Doxorubicin, and can be correlated with their increased bioavailability.https://www.mdpi.com/1424-8247/17/12/1630pentacyclic triterpenoidsPEGylated liposomesnanolipid complexesdiffraction light scatteringmelanoma B16-F10 and walker 256 carcinoma cellscell cycle arrest
spellingShingle Dumitriţa Rugină
Mihai Adrian Socaciu
Madalina Nistor
Zorita Diaconeasa
Mihai Cenariu
Flaviu Alexandru Tabaran
Carmen Socaciu
Liposomal and Nanostructured Lipid Nanoformulations of a Pentacyclic Triterpenoid Birch Bark Extract: Structural Characterization and In Vitro Effects on Melanoma B16-F10 and Walker 256 Tumor Cells Apoptosis
Pharmaceuticals
pentacyclic triterpenoids
PEGylated liposomes
nanolipid complexes
diffraction light scattering
melanoma B16-F10 and walker 256 carcinoma cells
cell cycle arrest
title Liposomal and Nanostructured Lipid Nanoformulations of a Pentacyclic Triterpenoid Birch Bark Extract: Structural Characterization and In Vitro Effects on Melanoma B16-F10 and Walker 256 Tumor Cells Apoptosis
title_full Liposomal and Nanostructured Lipid Nanoformulations of a Pentacyclic Triterpenoid Birch Bark Extract: Structural Characterization and In Vitro Effects on Melanoma B16-F10 and Walker 256 Tumor Cells Apoptosis
title_fullStr Liposomal and Nanostructured Lipid Nanoformulations of a Pentacyclic Triterpenoid Birch Bark Extract: Structural Characterization and In Vitro Effects on Melanoma B16-F10 and Walker 256 Tumor Cells Apoptosis
title_full_unstemmed Liposomal and Nanostructured Lipid Nanoformulations of a Pentacyclic Triterpenoid Birch Bark Extract: Structural Characterization and In Vitro Effects on Melanoma B16-F10 and Walker 256 Tumor Cells Apoptosis
title_short Liposomal and Nanostructured Lipid Nanoformulations of a Pentacyclic Triterpenoid Birch Bark Extract: Structural Characterization and In Vitro Effects on Melanoma B16-F10 and Walker 256 Tumor Cells Apoptosis
title_sort liposomal and nanostructured lipid nanoformulations of a pentacyclic triterpenoid birch bark extract structural characterization and in vitro effects on melanoma b16 f10 and walker 256 tumor cells apoptosis
topic pentacyclic triterpenoids
PEGylated liposomes
nanolipid complexes
diffraction light scattering
melanoma B16-F10 and walker 256 carcinoma cells
cell cycle arrest
url https://www.mdpi.com/1424-8247/17/12/1630
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