Preparation, Optimization, and In-Vitro Release Study of Abemaciclib-Loaded Chitosan Nanocarrier as a New Approach for Breast Cancer Treatment

Mohanad Mohammed Ali, S. Hussein-Al-Ali, Mike Kh. Haddad
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Abstract

Abemaciclib (Abm) is a CDK inhibitor that specifically targets the CDK4/6 cell cycle pathway and has potential anticancer activity. Unfortunately, it has a low solubility and dissolution rate. Abemaciclib Unfortunately, it has low solubility and dissolution rate. The aim of this study is to enhance the solubility of ABM by loading it onto a chitosan (CS) polymer. Polymer nanoparticle (NP) and Abm-CSNPs nanocomposites were prepared. Minitab 18 software was used to design 18 run samples to study the effects of CS, tripolyphosphate, and pH as independent variables on the loading efficiency and particle size (dependent variable). The response surface methodology (RSM) was also used to determine how the variables affected the response. The graphical analysis used surface plots, main effects plots, contour plots, and interaction graphs. The study includes F values, P values, variance inflation factors (VIFs), adjusted sums of square (Adj SSs), adjusted mean squares (Adj MSs) and square error of the coefficient (SE Coef). The carriers and loaded samples were also examined using the results of tests, including Fourier transform infrared spectroscopy, X-ray diffraction, and scanning electron microscopy. Furthermore, the release of Abm from Abm-CSNPs nanocomposite was studied in vitro. The results revealed an ability to produce particle sizes ranging from (168-192) nm and loading efficiencies from (56.7-62.1). Abm-CSNPs nanocomposite may be used as an alternative drug delivery system for Abm to increase the release time of Abm to 1400 minutes.
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作为乳腺癌治疗新方法的阿贝昔利布负载壳聚糖纳米载体的制备、优化和体外释放研究
Abemaciclib(ABM)是一种CDK抑制剂,专门针对CDK4/6细胞周期途径,具有潜在的抗癌活性。本研究的目的是通过在壳聚糖(CS)聚合物上负载 ABM 来提高其溶解度。本研究制备了聚合物纳米粒子(NP)和 Abm-CSNPs 纳米复合材料。使用 Minitab 18 软件设计了 18 个运行样本,以研究 CS、三聚磷酸钠和 pH 作为自变量对负载效率和粒度(因变量)的影响。图形分析使用了表面图、主效应图、等值线图和交互作用图。研究包括 F 值、P 值、方差膨胀因子(VIF)、调整后平方和(Adj SS)、调整后均方差(Adj MS)和系数平方误差(SE Coef)。还利用傅立叶变换红外光谱、X 射线衍射和扫描电子显微镜等测试结果对载体和负载样品进行了检验。此外,还在体外研究了 Abm-CSNPs 纳米复合材料释放阿维菌素的情况。结果表明,Abm-CSNPs 纳米复合材料能够产生粒径为(168-192)纳米的颗粒,负载效率为(56.7-62.1)。
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