Atorvastatin-loaded cubosome: a repurposed targeted delivery systems for enhanced targeting against breast cancer.

IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY
Eman M El-Marakby, Hend Fayez, M A Motaleb, Mai Mansour
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引用次数: 0

Abstract

Cancer ranks as one of the most challenging illnesses to deal with because progressive phenotypic and genotypic alterations in cancer cells result in resistance and recurrence. Thus, the creation of novel medications or alternative therapy approaches is mandatory. Repurposing of old drugs is an attractive approach over the traditional drug discovery process in terms of shorter drug development duration, low-cost, highly efficient and minimum risk of failure. In this study Atorvastatin, a statin drug used to treat abnormal cholesterol levels and prevent cardiovascular disease in people at high risk, was introduced and encapsulated in cubic liquid crystals as anticancer candidate aiming at sustaining its release and achieving better cellular uptake in cancer cells. The cubic liquid crystals were successfully prepared and optimized with an entrapment effieciency of 73.57% ±1.35 and particle size around 200 nm. The selected formulae were effectively doped with radioactive iodine 131I to enable the noninvasive visualization and trafficking of the new formulae. The in vivo evaluation in solid tumor bearing mice was conducted for comparing131I-Atorvastatin solution,131I-Atorvastatin loaded cubosome and 131I-Atorvastatin chitosan coated cubosome. The in vivo biodistribution study revealed that tumor radioactivity uptake of 131I-Atorvastatin cubosome and chitosan coated cubosome exhibited high accumulation in tumor tissues (target organ) scoring ID%/g of 5.67 ± 0.2 and 5.03 ± 0.1, respectively 1h post injection compared to drug solution which recorded 3.09 ± 0.05% 1h post injection. Concerning the targeting efficiency, the target/non target ratio for 131I-Atorvastatin chitosan coated cubosome was higher than that of 131I-Atorvastatin solution and 131I ATV-loaded cubosome at all time intervals and recorded T/NT ratio of 2.908 2h post injection.

阿托伐他汀载体立方体:增强乳腺癌靶向性的再利用靶向递送系统。
癌症是最具挑战性的疾病之一,因为癌细胞表型和基因型的逐渐改变会导致抗药性和复发。因此,必须开发新型药物或替代治疗方法。与传统的药物研发过程相比,旧药再利用是一种极具吸引力的方法,因为它能缩短药物研发时间、降低成本、提高效率并将失败风险降至最低。阿托伐他汀是一种他汀类药物,用于治疗胆固醇水平异常和预防高危人群的心血管疾病,本研究将阿托伐他汀作为抗癌候选药物引入并封装在立方液晶中,目的是使其持续释放并更好地被癌细胞吸收。成功制备并优化的立方液晶的包封率为 73.57% ±1.35,粒径约为 200 纳米。所选配方有效地掺入了放射性碘 131I,从而实现了新配方的无创可视化和迁移。对 131I 阿托伐他汀溶液、131I-阿托伐他汀负载立方体和 131I 阿托伐他汀壳聚糖包覆立方体进行了实体瘤小鼠体内评估。体内生物分布研究表明,131I-阿托伐他汀立方体和壳聚糖包裹的立方体在肿瘤组织(靶器官)中的放射性吸收率较高,注射后1小时的ID%/g分别为5.67 ± 0.2和5.03 ± 0.1,而药物溶液在注射后1小时的ID%/g为3.09 ± 0.05%。在靶向效率方面,131I-阿托伐他汀壳聚糖包裹的立方体在所有时间间隔内的靶向/非靶向比率均高于131I-阿托伐他汀溶液和131I ATV负载的立方体,注射后2小时的T/NT比率为2.908。
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来源期刊
CiteScore
5.90
自引率
2.90%
发文量
82
审稿时长
1 months
期刊介绍: Pharmaceutical Development & Technology publishes research on the design, development, manufacture, and evaluation of conventional and novel drug delivery systems, emphasizing practical solutions and applications to theoretical and research-based problems. The journal aims to publish significant, innovative and original research to advance the frontiers of pharmaceutical development and technology. Through original articles, reviews (where prior discussion with the EIC is encouraged), short reports, book reviews and technical notes, Pharmaceutical Development & Technology covers aspects such as: -Preformulation and pharmaceutical formulation studies -Pharmaceutical materials selection and characterization -Pharmaceutical process development, engineering, scale-up and industrialisation, and process validation -QbD in the form a risk assessment and DoE driven approaches -Design of dosage forms and drug delivery systems -Emerging pharmaceutical formulation and drug delivery technologies with a focus on personalised therapies -Drug delivery systems research and quality improvement -Pharmaceutical regulatory affairs This journal will not consider for publication manuscripts focusing purely on clinical evaluations, botanicals, or animal models.
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