Development of Folic Acid Functionalized Bilosomes for Delivery of Vorinostat to Breast Cancer Cells: Characterization and Cytocidal Effects on MCF-7 and 4T1 Breast Cancer Cell Lines

Purpose: Breast cancer is a prevalent form of cancer in woman. Vorinostat (VOR) is a chemotherapeutic drug that has been utilized for treatment of breast cancer, but its effectiveness is limited due to low bioavailability and several side effects. The primary aim of this study is to prepare folic ac...

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Main Authors: Alireza Rashidi, Somayeh Taymouri, Mahboubeh Rostami, Mina Mirian
Format: Article
Language:English
Published: Tabriz University of Medical Sciences 2025-04-01
Series:Advanced Pharmaceutical Bulletin
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Online Access:https://apb.tbzmed.ac.ir/PDF/apb-15-82.pdf
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author Alireza Rashidi
Somayeh Taymouri
Mahboubeh Rostami
Mina Mirian
author_facet Alireza Rashidi
Somayeh Taymouri
Mahboubeh Rostami
Mina Mirian
author_sort Alireza Rashidi
collection DOAJ
description Purpose: Breast cancer is a prevalent form of cancer in woman. Vorinostat (VOR) is a chemotherapeutic drug that has been utilized for treatment of breast cancer, but its effectiveness is limited due to low bioavailability and several side effects. The primary aim of this study is to prepare folic acid conjugated pegylated bilosomes containing VOR (FA-PEG- bilosomes) for the selective targeting of breast cancer cells with the FA receptor expression. Accordingly, lithocholic acid was used as a bile acid in bilosomes due to its anti-cancer and anti-proliferation effects. Methods: VOR loaded bilosomes were prepared using the thin-film hydration method and optimized by applying two-level fractional factorial design. Various properties of the considered bilosomes, including particle size, zeta potential, polydispersity index (PdI), encapsulation efficiency (EE) % and drug loading (DL) %, were then investigated and synthesized FA-PEG-Cholesterol was incorporated in the optimized bilosomes. The anti-cancer efficacy of VOR loaded FA-PEG- bilosomes was also evaluated in vitro using the MCF-7 and 4T1 breast cancer cell lines. Furthermore, drug free FA-PEG-bilosomes and bilosomes were evaluated for biocompatibility in the L929 cell line. Results: The optimized VOR loaded bilosomes exhibited spherical particles with the size of 305.33±18.50 nm, PdI of 0.37±0.03, zeta potential of -17.66±0.15 mV, EE of 92.91±0.22 % and DL% of 23.64±0.04%. Incorporation of FA-PEG-cholesterol in nanobilosomes increased the particle size and absolute value of zeta potential. In vitro cytotoxicity study also revealed that VOR loaded FA- PEG-bilosomes demonstrated a greater cytotoxic effect, as compared to the free VOR and VOR- bilosomes in both MCF-7 and 4T1 cancer cells. Conclusion: This showed that FA- PEG-bilosomes could be a promising formulation for the treatment of FA (+) tumors.
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spelling doaj-art-3a5b0f5468024bc8ae82636fe8250be82025-08-20T02:41:33ZengTabriz University of Medical SciencesAdvanced Pharmaceutical Bulletin2228-58812251-73082025-04-01151829410.34172/apb.43232apb-43232Development of Folic Acid Functionalized Bilosomes for Delivery of Vorinostat to Breast Cancer Cells: Characterization and Cytocidal Effects on MCF-7 and 4T1 Breast Cancer Cell LinesAlireza Rashidi0Somayeh Taymouri1Mahboubeh Rostami2Mina Mirian3Department of Pharmaceutics, School of Pharmacy and Novel Drug Delivery Systems Research Centre, Isfahan University of Medical Sciences, Isfahan, Iran.Department of Pharmaceutics, School of Pharmacy and Novel Drug Delivery Systems Research Centre, Isfahan University of Medical Sciences, Isfahan, Iran.Department of Medicinal Chemistry, School of Pharmacy and Novel Drug Delivery Systems Research Centre, Isfahan University of Medical Sciences, Isfahan, Iran.Department of Biotechnology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.Purpose: Breast cancer is a prevalent form of cancer in woman. Vorinostat (VOR) is a chemotherapeutic drug that has been utilized for treatment of breast cancer, but its effectiveness is limited due to low bioavailability and several side effects. The primary aim of this study is to prepare folic acid conjugated pegylated bilosomes containing VOR (FA-PEG- bilosomes) for the selective targeting of breast cancer cells with the FA receptor expression. Accordingly, lithocholic acid was used as a bile acid in bilosomes due to its anti-cancer and anti-proliferation effects. Methods: VOR loaded bilosomes were prepared using the thin-film hydration method and optimized by applying two-level fractional factorial design. Various properties of the considered bilosomes, including particle size, zeta potential, polydispersity index (PdI), encapsulation efficiency (EE) % and drug loading (DL) %, were then investigated and synthesized FA-PEG-Cholesterol was incorporated in the optimized bilosomes. The anti-cancer efficacy of VOR loaded FA-PEG- bilosomes was also evaluated in vitro using the MCF-7 and 4T1 breast cancer cell lines. Furthermore, drug free FA-PEG-bilosomes and bilosomes were evaluated for biocompatibility in the L929 cell line. Results: The optimized VOR loaded bilosomes exhibited spherical particles with the size of 305.33±18.50 nm, PdI of 0.37±0.03, zeta potential of -17.66±0.15 mV, EE of 92.91±0.22 % and DL% of 23.64±0.04%. Incorporation of FA-PEG-cholesterol in nanobilosomes increased the particle size and absolute value of zeta potential. In vitro cytotoxicity study also revealed that VOR loaded FA- PEG-bilosomes demonstrated a greater cytotoxic effect, as compared to the free VOR and VOR- bilosomes in both MCF-7 and 4T1 cancer cells. Conclusion: This showed that FA- PEG-bilosomes could be a promising formulation for the treatment of FA (+) tumors.https://apb.tbzmed.ac.ir/PDF/apb-15-82.pdfbreast cancerbilosomeslithocholic acidvorinostatfolate receptormtt assay
spellingShingle Alireza Rashidi
Somayeh Taymouri
Mahboubeh Rostami
Mina Mirian
Development of Folic Acid Functionalized Bilosomes for Delivery of Vorinostat to Breast Cancer Cells: Characterization and Cytocidal Effects on MCF-7 and 4T1 Breast Cancer Cell Lines
Advanced Pharmaceutical Bulletin
breast cancer
bilosomes
lithocholic acid
vorinostat
folate receptor
mtt assay
title Development of Folic Acid Functionalized Bilosomes for Delivery of Vorinostat to Breast Cancer Cells: Characterization and Cytocidal Effects on MCF-7 and 4T1 Breast Cancer Cell Lines
title_full Development of Folic Acid Functionalized Bilosomes for Delivery of Vorinostat to Breast Cancer Cells: Characterization and Cytocidal Effects on MCF-7 and 4T1 Breast Cancer Cell Lines
title_fullStr Development of Folic Acid Functionalized Bilosomes for Delivery of Vorinostat to Breast Cancer Cells: Characterization and Cytocidal Effects on MCF-7 and 4T1 Breast Cancer Cell Lines
title_full_unstemmed Development of Folic Acid Functionalized Bilosomes for Delivery of Vorinostat to Breast Cancer Cells: Characterization and Cytocidal Effects on MCF-7 and 4T1 Breast Cancer Cell Lines
title_short Development of Folic Acid Functionalized Bilosomes for Delivery of Vorinostat to Breast Cancer Cells: Characterization and Cytocidal Effects on MCF-7 and 4T1 Breast Cancer Cell Lines
title_sort development of folic acid functionalized bilosomes for delivery of vorinostat to breast cancer cells characterization and cytocidal effects on mcf 7 and 4t1 breast cancer cell lines
topic breast cancer
bilosomes
lithocholic acid
vorinostat
folate receptor
mtt assay
url https://apb.tbzmed.ac.ir/PDF/apb-15-82.pdf
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AT somayehtaymouri developmentoffolicacidfunctionalizedbilosomesfordeliveryofvorinostattobreastcancercellscharacterizationandcytocidaleffectsonmcf7and4t1breastcancercelllines
AT mahboubehrostami developmentoffolicacidfunctionalizedbilosomesfordeliveryofvorinostattobreastcancercellscharacterizationandcytocidaleffectsonmcf7and4t1breastcancercelllines
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