Hansen parameters and GastroPlus assisted optimized topical elastic liposomes to treat breast cancer using a novel isatin derivative

IF 5.3 2区化学 Q2 CHEMISTRY, MULTIDISCIPLINARY

Arabian Journal of Chemistry Pub Date : 2024-10-18 DOI:10.1016/j.arabjc.2024.106028

Mohammad A. Altamimi , Afzal Hussain , Mohammed M. Alanazi , Dhafer Alotaibi , Saeed Ali Syed , Ahmed Bari

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Abstract

Breast cancer treatment is a global health challenge using conventional toxic chemotherapeutic agents. A novel isatin could be a promising alternative. An isatin derivative (TM-19) was synthesized and characterized using NMR (nuclear magnetic resonance), mass spectrometry, Fourier transform infrared (FTIR), and differential scanning calorimetry (DSC). HSPiP and GastroPlus predictive software were used to predict suitable solvents for solubility and in vivo oral pharmacokinetics in humans (fasted condition), respectively. Based on predictive findings, topical elastic liposomes (phosphatidylcholine as PC and span 80 by film hydration method) was prepared, characterized, and optimized using QbD (quality by design). QbD identified the impact of composition on response variables (Y₁ for size, Y₂ for polydispersity index, Y₃ for zeta potential, and Y₄ for %EE). In vitro cytotoxicity study was carried out against MCF-7 cell lines. Low molecular weight and lipophilic TM-19 was crystalline in nature (255 g/mol). GastroPlus program predicted limited in vivo dissolution and poor oral absorption (10.4 %). Results confirmed the highest TM-19 solubility in DMSO (dimethyl sulfoxide) ˃ chloroform ˃ PEG 400 (polyethylene glycol 400). Considering experimental and predicted data, topical delivery of TM-19 using optimized (desirability parameter value = 0.97) elastic liposomes (TF1) was quite promising due to optimal size (344 nm), high %EE (61.7 %), low PDI (0.45), and optimal zeta potential (− 12.34 mV). TM-19 loaded TF1 elicited concentration dependent cytotoxic effect (˃ 90 % at 10 µM) against MCF-7 as compared to TM-19 suspension.

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利用新型异汀衍生物治疗乳腺癌的汉森参数和 GastroPlus 辅助优化局部弹性脂质体

使用传统的有毒化疗药物治疗乳腺癌是一项全球性的健康挑战。新型异靛红可能是一种有前途的替代品。我们合成了一种isatin衍生物（TM-19），并使用核磁共振（NMR）、质谱分析、傅立叶变换红外（FTIR）和差示扫描量热法（DSC）对其进行了表征。HSPiP 和 GastroPlus 预测软件分别用于预测合适的溶剂在人体（空腹状态）中的溶解度和体内口服药代动力学。根据预测结果，采用 QbD（质量源于设计）方法制备、表征和优化了局部弹性脂质体（磷脂酰胆碱作为 PC，span 80 采用薄膜水合法）。QbD 确定了组成对响应变量的影响（Y1 为大小，Y2 为多分散指数，Y3 为 zeta 电位，Y4 为 %EE）。对 MCF-7 细胞系进行了体外细胞毒性研究。低分子量、亲油的 TM-19 呈晶体状（255 克/摩尔）。GastroPlus 程序预测其体内溶解度有限，口服吸收率低（10.4%）。结果证实，TM-19 在 DMSO（二甲基亚砜）˃ 氯仿 ˃ PEG 400（聚乙二醇 400）中的溶解度最高。考虑到实验数据和预测数据，使用优化的（可取参数值 = 0.97）弹性脂质体（TF1）局部给药 TM-19，由于其具有最佳尺寸（344 nm）、高 %EE（61.7 %）、低 PDI（0.45）和最佳 zeta 电位（- 12.34 mV），因此前景非常广阔。与 TM-19 悬浮液相比，TM-19 负载的 TF1 对 MCF-7 具有浓度依赖性细胞毒性作用（10 µM 时为 90%）。

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来源期刊

Arabian Journal of Chemistry CHEMISTRY, MULTIDISCIPLINARY-

CiteScore

10.80

自引率

3.30%

发文量

763

审稿时长

63 days

期刊介绍： The Arabian Journal of Chemistry is an English language, peer-reviewed scholarly publication in the area of chemistry. The Arabian Journal of Chemistry publishes original papers, reviews and short reports on, but not limited to: inorganic, physical, organic, analytical and biochemistry. The Arabian Journal of Chemistry is issued by the Arab Union of Chemists and is published by King Saud University together with the Saudi Chemical Society in collaboration with Elsevier and is edited by an international group of eminent researchers.