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.

IF 3.1 Q2 PHARMACOLOGY & PHARMACY

Advanced pharmaceutical bulletin Pub Date : 2024-12-14 eCollection Date: 2025-04-01 DOI:10.34172/apb.43232

Alireza Rashidi, Somayeh Taymouri, Mahboubeh Rostami, Mina Mirian

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Abstract

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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叶酸功能化的卵磷脂体用于向乳腺癌细胞递送伏立诺他：表征及其对MCF-7和4T1乳腺癌细胞系的细胞杀伤作用。

目的：乳腺癌是女性中常见的一种癌症。伏立诺他（VOR）是一种用于治疗乳腺癌的化疗药物，但由于生物利用度低和一些副作用，其有效性受到限制。本研究的主要目的是制备含有VOR的叶酸偶联聚乙二醇化胆囊体（FA- peg -胆囊体），用于选择性靶向FA受体表达的乳腺癌细胞。因此，石胆酸因其抗癌和抗增殖作用而被用作胆汁酸。方法：采用薄膜水化法制备载VOR的胆小体，并采用双水平分数因子设计对其进行优化。然后研究了所考虑的胆囊体的各种特性，包括粒径、zeta电位、多分散性指数（PdI）、包封效率（EE） %和载药量（DL） %，并将fa - peg -胆固醇掺入优化的胆囊体中。我们还利用MCF-7和4T1乳腺癌细胞系，在体外评估了VOR负载FA-PEG-胆小体的抗癌效果。此外，对无药fa - peg -胆囊体和胆囊体在L929细胞系中的生物相容性进行了评价。结果：优化后的VOR负载的小体呈球形，粒径为305.33±18.50 nm， PdI为0.37±0.03，zeta电位为-17.66±0.15 mV， EE为92.91±0.22%，DL%为23.64±0.04%。fa - peg -胆固醇在纳米胆管体中的掺入增加了粒子大小和zeta电位的绝对值。体外细胞毒性研究也显示，在MCF-7和4T1癌细胞中，与游离的VOR和VOR- bilosomes相比，装载VOR的FA- PEG-bilosomes表现出更大的细胞毒性作用。结论：FA- peg -二脂体是治疗FA（+）肿瘤的理想制剂。

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