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口服索拉非尼负载型微乳用于乳腺癌:来自体外评价和药代动力学研究的证据。

Oral sorafenib-loaded microemulsion for breast cancer: evidences from the in-vitro evaluations and pharmacokinetic studies.

机构信息

Department of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, Bandarsindri, Ajmer, Rajasthan, 305817, India.

Department of Pharmaceutics, College of Pharmacy, University of Hafr Al-Batin, Al Jamiah, Hafr Al Batin, 39524, Saudi Arabia.

出版信息

Sci Rep. 2022 Aug 12;12(1):13746. doi: 10.1038/s41598-022-17333-6.

DOI:10.1038/s41598-022-17333-6
PMID:35962160
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9374710/
Abstract

Sorafenib tosylate (SFB) is a multikinase inhibitor that inhibits tumour growth and proliferation for the management of breast cancer but is also associated with issues like toxicity and drug resistance. Also, being a biopharmaceutical class II (BCS II) drug, its oral bioavailability is the other challenge. Henceforth, this report intended to encapsulate SFB into a biocompatible carrier with biodegradable components, i.e., phospholipid. The microemulsion of the SFB was prepared and characterized for the surface charge, morphology, micromeritics and drug release studies. The cell viability assay was performed on 4T1 cell lines and inferred that the IC value of sorafenib-loaded microemulsion (SFB-loaded ME) was enhanced compared to the naïve SFB at the concentrations of about 0.75 µM. More drug was available for the pharmacological response, as the protein binding was notably decreased, and the drug from the developed carriers was released in a controlled manner. Furthermore, the pharmacokinetic studies established that the developed nanocarrier was suitable for the oral administration of a drug by substantially enhancing the bioavailability of the drug to that of the free SFB. The results bring forth the preliminary evidence for the future scope of SFB as a successful therapeutic entity in its nano-form for effective and safer cancer chemotherapy via the oral route.

摘要

甲苯磺酸索拉非尼(SFB)是一种多激酶抑制剂,可抑制肿瘤生长和增殖,用于治疗乳腺癌,但也存在毒性和耐药性等问题。此外,作为一种生物制药 II 类(BCS II)药物,其口服生物利用度也是另一个挑战。因此,本报告旨在将 SFB 包封到具有生物降解成分的生物相容性载体中,即磷脂。制备并表征了 SFB 的微乳液,以研究其表面电荷、形态、微粉学和药物释放研究。在 4T1 细胞系上进行了细胞活力测定,并推断与游离 SFB 相比,载有索拉非尼的微乳液(SFB-loaded ME)的 IC 值在约 0.75µM 的浓度下有所提高。由于蛋白结合显著降低,并且开发的载体中的药物以受控方式释放,因此有更多的药物可用于药理反应。此外,药代动力学研究表明,所开发的纳米载体适合通过口服给予药物,从而大大提高药物的生物利用度,使其达到游离 SFB 的水平。这些结果为 SFB 在纳米形式下作为一种成功的治疗实体的未来前景提供了初步证据,可通过口服途径进行有效和更安全的癌症化疗。

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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27cf/9374710/4ca227834d54/41598_2022_17333_Fig2_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27cf/9374710/eacbba46aec2/41598_2022_17333_Fig4_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27cf/9374710/f50a0f13a40f/41598_2022_17333_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27cf/9374710/a598ace30bbf/41598_2022_17333_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27cf/9374710/d6ced557cd41/41598_2022_17333_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27cf/9374710/fb4d106865ca/41598_2022_17333_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27cf/9374710/afc926575f71/41598_2022_17333_Fig11_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27cf/9374710/c6cafbe581e0/41598_2022_17333_Fig13_HTML.jpg

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