Oral linalool-based nanoemulsion of acalabrutinib for ameliorating its oral bioavailability and in vitro anticancer potential in T lymphoblast cell lines

IF 2.2 4区化学 Q3 CHEMISTRY, PHYSICAL

Colloid and Polymer Science Pub Date : 2024-07-04 DOI:10.1007/s00396-024-05290-7

Arti Shettiwar, Ujala Gupta, Essha Chatterjee, Bhagyashree Patra, Mayur Aalhate, Srushti Mahajan, Indrani Maji, Neelesh Kumar Mehra, Santosh Kumar Guru, Pankaj Kumar Singh

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Abstract

Acalabrutinib (ACL) was approved in the United States in the year of 2017 and 2019 for the treatment of chronic lymphocytic leukemia (CLL) and relapsed mantle cell lymphoma (MCL). Low-energy method was employed to curate nanoemulsion (NE) for which various components were screened through solubility study and optimization was done through a pseudo-ternary phase diagram. The NE was evaluated for its droplet size, polydispersity index (PDI), transmittance, morphology, rheology, robustness to dilution, the effect of pH, storage stability, and ex vivo permeation study. The optimized ACL-NE demonstrated an appropriate droplet size (94.35 ± 0.3 nm), PDI (0.27 ± 0.03), and an entrapment efficiency of 67.38 ± 2.69%. It showed non-Newtonian (shear thinning behavior) due to reduced viscosity with an increasing shear rate. The apparent permeability was 3.09-fold higher for ACL-NE than ACL suspension. An in vitro drug release study depicted a higher release of ACL (71.10 ± 10.99%) from the optimized NE in a sustained fashion than the suspension (49.01 ± 1.65%). A dose-dependent cytotoxicity was observed in MOLT-4 and HH-cell lines where the IC50 values of ACL were 5.62- and 16.49-fold reduced when encapsulated in oil globules for the respective cell lines. Blank-NE did cause a reduction in cellular toxicity at higher doses. A 7.31- and 5.1-fold increase in C_max and bioavailability was noted between ACL suspension and ACL-NE.

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基于芳樟醇的阿卡布替尼口服纳米乳液可改善其口服生物利用度和在 T 淋巴母细胞系中的体外抗癌潜力

阿卡布替尼（ACL）于2017年和2019年在美国获批用于治疗慢性淋巴细胞白血病（CLL）和复发套细胞淋巴瘤（MCL）。研究人员采用低能法制备了纳米乳液（NE），通过溶解度研究筛选了其中的各种成分，并通过伪三元相图进行了优化。对纳米乳液的液滴大小、多分散指数（PDI）、透光率、形态、流变性、对稀释的稳定性、pH 值的影响、储存稳定性和体内外渗透研究进行了评估。优化后的 ACL-NE 显示出适当的液滴大小（94.35 ± 0.3 nm）、PDI（0.27 ± 0.03）和 67.38 ± 2.69% 的夹带效率。由于粘度随剪切速率的增加而降低，它呈现出非牛顿性（剪切稀化行为）。ACL-NE 的表观渗透性比 ACL 悬浮液高 3.09 倍。体外药物释放研究表明，从优化的 NE 中持续释放的 ACL（71.10 ± 10.99%）高于悬浮液（49.01 ± 1.65%）。在 MOLT-4 和 HH 细胞系中观察到了剂量依赖性细胞毒性，当 ACL 被包裹在油球中时，其 IC50 值分别降低了 5.62 倍和 16.49 倍。在较高剂量下，Blank-NE 确实会降低细胞毒性。ACL 悬浮液和 ACL-NE 的 Cmax 和生物利用度分别增加了 7.31 倍和 5.1 倍。

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来源期刊

Colloid and Polymer Science 化学-高分子科学

CiteScore

4.60

自引率

4.20%

发文量

111

审稿时长

2.2 months

期刊介绍： Colloid and Polymer Science - a leading international journal of longstanding tradition - is devoted to colloid and polymer science and its interdisciplinary interactions. As such, it responds to a demand which has lost none of its actuality as revealed in the trends of contemporary materials science.