Kumar Rohit, Kumar Anurag, Kumar Dharmendra, Yadav Sneha, Shrivastava Neeraj Kumar, Singh Jyoti, Sonkar Archana Bharti, Verma Pratibha, Arya Dilip Kumar, Kaithwas Gaurav, Agrarwal Ashish Kumar, Singh Sanjay
Department of Pharmaceutical Sciences, School of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University (A Central University), Vidya Vihar, Raebareli Road, Lucknow 226025, India.
Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (BHU), Varanasi 221005, India.
Pharmaceutics. 2024 Jul 9;16(7):913. doi: 10.3390/pharmaceutics16070913.
Our hypothesis posited that incorporating alpha-linolenic acid (ALA) into liposomes containing Paclitaxel (PTX) could augment cellular uptake, decrease the therapeutic dosage, and alleviate PTX-related side effects. Our investigation encompassed characterization of the liposomal formulation, encompassing aspects like particle size, surface morphology, chemical structure, drug release kinetics, and stability. Compatibility studies were performed through Fourier transform infrared spectroscopy (FTIR). By utilizing the Box-Behnken design (BBD), we developed ALA-based liposomes with satisfactory particle size and entrapment efficiency. It is noteworthy that ALA incorporation led to a slight increase in particle size but did not notably affect drug entrapment. In vitro drug release assessments unveiled a sustained release pattern, with ALA-PTX liposomes demonstrating release profiles comparable to PTX liposomes. Morphological examinations confirmed the spherical structure of the liposomes, indicating that substituting ALA with phosphatidylcholine did not alter the physicochemical properties. Cellular uptake investigations showcased enhanced uptake of ALA-based liposomes in contrast to PTX liposomes, likely attributed to the heightened fluidity conferred by ALA. Efficacy against MCF-7 cells demonstrated concentration-dependent reductions in cell viability, with ALA-PTX liposomes exhibiting the lowest IC50 value. Morphological analysis confirmed apoptotic changes in cells treated with all formulations, with ALA-PTX liposomes eliciting more pronounced changes, indicative of enhanced anticancer efficacy.
我们的假设是,将α-亚麻酸(ALA)掺入含有紫杉醇(PTX)的脂质体中,可以增加细胞摄取,降低治疗剂量,并减轻与PTX相关的副作用。我们的研究包括脂质体制剂的表征,涵盖粒径、表面形态、化学结构、药物释放动力学和稳定性等方面。通过傅里叶变换红外光谱(FTIR)进行相容性研究。利用Box-Behnken设计(BBD),我们开发了具有令人满意的粒径和包封率的基于ALA的脂质体。值得注意的是,掺入ALA导致粒径略有增加,但对药物包封没有显著影响。体外药物释放评估揭示了一种持续释放模式,ALA-PTX脂质体的释放曲线与PTX脂质体相当。形态学检查证实了脂质体的球形结构,表明用ALA替代磷脂酰胆碱不会改变其物理化学性质。细胞摄取研究表明,与PTX脂质体相比,基于ALA的脂质体的摄取增强,这可能归因于ALA赋予的更高流动性。对MCF-7细胞的疗效表明,细胞活力呈浓度依赖性降低,ALA-PTX脂质体表现出最低的IC50值。形态学分析证实了用所有制剂处理的细胞中的凋亡变化,ALA-PTX脂质体引起更明显的变化,表明抗癌疗效增强。