Baghdadi Rehab A, Abdalla Ashraf N, Abourehab Mohammed A S, Tulbah Alaa S
Department of Pharmaceutical Sciences, College of Pharmacy, Umm Al-Qura University, Makkah, KSA.
Department of Pharmaceutics and Industrial Pharmacy, College of Pharmacy, Minia University, Minia, Egypt.
J Taibah Univ Med Sci. 2024 Jul 22;19(4):806-815. doi: 10.1016/j.jtumed.2024.07.002. eCollection 2024 Aug.
BACKGROUND/AIM: Dasatinib (DS), a second-generation tyrosine kinase inhibitor, functions as a multi-target small-molecule drug via targeting various tyrosine kinases involved in neoplastic cell growth. DS inhibits cancer cell replication and migration, and induces tumor cell apoptosis in a variety of solid tumors. However, it is poorly soluble in water under some pH values. Therefore, the development of a DS-containing, self-emulsifying, drug delivery system (SeDDs) could help overcome these problems in treating cancer cells.
Various SeDD formulations loaded with DS were developed with isopropyl myristate (oil phase), Labrafil (surfactant), and polyethylene glycol (co-surfactant). The physicochemical properties of the formulations were assessed according to droplet size, encapsulation efficiency, and in vitro drug release. The cytotoxicity of the formulations on the cancer cell lines HT29 and SW420 (human colorectal carcinoma), and MCF7 (human breast adenocarcinoma), in addition to MRC5 normal human fetal lung fibroblasts, was evaluated to assess selectivity.
The DS-SeDD formulation showed favorable particle size, encapsulation efficiency, and in vitro drug release. The anti-cancer potency of DS-SeDDs had greater cytotoxicity effects than pure DA on the three cancer cell lines, MCF7, HT29, and SW420l.
The developed DS-SeDD formulations may potentially be an effective sustained drug delivery method for cancer therapy.
背景/目的：达沙替尼（DS）是一种第二代酪氨酸激酶抑制剂，通过靶向参与肿瘤细胞生长的各种酪氨酸激酶发挥多靶点小分子药物的作用。DS抑制癌细胞的复制和迁移，并在多种实体瘤中诱导肿瘤细胞凋亡。然而，在某些pH值下它在水中的溶解度较差。因此，开发一种含DS的自乳化药物递送系统（SeDDs）有助于克服在治疗癌细胞方面的这些问题。
用肉豆蔻酸异丙酯（油相）、Labrafil（表面活性剂）和聚乙二醇（助表面活性剂）开发了多种负载DS的SeDD制剂。根据粒径、包封率和体外药物释放来评估制剂的物理化学性质。评估了制剂对癌细胞系HT29和SW420（人结肠直肠癌）、MCF7（人乳腺腺癌）以及MRC5正常人胎儿肺成纤维细胞的细胞毒性，以评估其选择性。
DS-SeDD制剂显示出良好的粒径、包封率和体外药物释放。DS-SeDDs的抗癌效力对三种癌细胞系MCF7、HT29和SW420l的细胞毒性作用比纯DS更大。
所开发的DS-SeDD制剂可能是一种有效的癌症治疗持续药物递送方法。
