Afzal Obaid, Akhter Md Habban, Ahmad Irfan, Muzammil Khursheed, Dawria Adam, Zeyaullah Mohammad, Altamimi Abdulmalik S A, Khalilullah Habibullah, Mir Najib Ullah Shehla Nasar, Rahman Mohammad Akhlaquer, Ali Abuzer, Shahzad Naiyer, Jaremko Mariusz, Emwas Abdul-Hamid, Abdel Aziz Ibrahim Ibrahim
Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia.
School of Pharmaceutical and Population Health Informatics (SoPPHI), DIT University, Dehradun 248009, India.
Pharmaceutics. 2022 Aug 16;14(8):1711. doi: 10.3390/pharmaceutics14081711.
β−sitosterol is the most abundant type of phytosterol or plant sterol and can be found in various plant dietary sources including natural oils, soy products, and nuts. Numerous studies have demonstrated the potential therapeutic and clinical applications of β−sitosterol including lowering low-density lipoprotein and cholesterol levels, scavenging free radicals in the body, and interestingly, treating and preventing cancer. This study focuses on synthesizing and characterizing β−sitosterol encapsulated Alginate/Chitosan nanoparticles (β−sito−Alg/Ch/NPs) and evaluating their effectiveness in breast cancer treatment and their pharmacokinetic profile in vivo. The synthesized NPs, which incurred a mean size of 25 ± 1 nm, were extensively characterized in vitro for various parameters including surface charge and morphology. The NPs were further analyzed using DSC, FT-IR, thermogravimetry and X-ray diffraction studies. The release of β−sito from NPs was carried out in a bio-relevant medium of pH 7.4 and pH 5.5 and samples were drawn off and analyzed under time frames of 0, 8, 16, 32, 64, 48, 80, and 96 h, and the best kinetic release model was developed after fitting drug release data into different kinetic models. The metabolic activity of MCF-7 cells treated with the prepared formulation was assessed. The radical scavenging potential of β−sito−Alg/Ch/NPs was also studied. The pharmacokinetic parameters including Cmax, Tmax, half-life (t1/2), and bioavailability were measured for β−sito−Alg/Ch/NPs as compared to β−sito−suspension. The β−sito−Alg/Ch/NPs stability was assessed at biological pH 7.4. The % drug release in PBS of pH 7.4 reportedly has shown 41 ± 6% vs. 11 ± 1% from β−sito−Alg/Ch/NPs and β−sito−suspension. In acidic pH 5.5 mimicking the tumor microenvironment has shown 75 ± 9% vs. 12 ± 4% drug release from β−sito−Alg/Ch/NPs and β−sito−suspension. When compared to the β−sito−suspension, the β−sito−Alg/Ch/NPs demonstrated greater cytotoxicity (p < 0.05) and ~3.41-fold higher oral bioavailability. Interestingly, this work demonstrated that β−sito−Alg/Ch/NPs showed higher cytotoxicity due to improved bioavailability and antioxidant potential compared to the β−sito−suspension.
β-谷甾醇是植物甾醇或植物固醇中含量最丰富的类型，可在各种植物性饮食来源中找到，包括天然油脂、豆制品和坚果。大量研究表明了β-谷甾醇的潜在治疗和临床应用，包括降低低密度脂蛋白和胆固醇水平、清除体内自由基，有趣的是，还能治疗和预防癌症。本研究着重于合成和表征包裹β-谷甾醇的海藻酸盐/壳聚糖纳米颗粒（β-sito-Alg/Ch/NPs），并评估其在乳腺癌治疗中的有效性及其体内药代动力学特征。合成的纳米颗粒平均尺寸为25±1纳米，在体外对包括表面电荷和形态在内的各种参数进行了广泛表征。使用差示扫描量热法（DSC）、傅里叶变换红外光谱（FT-IR）、热重分析和X射线衍射研究对纳米颗粒进行了进一步分析。β-sito从纳米颗粒中的释放是在pH 7.4和pH 5.5的生物相关介质中进行的，在0、8、16、32、64、48、80和96小时的时间范围内抽取样品并进行分析，将药物释放数据拟合到不同的动力学模型后建立了最佳动力学释放模型。评估了用制备的制剂处理的MCF-7细胞的代谢活性。还研究了β-sito-Alg/Ch/NPs的自由基清除潜力。与β-sito混悬液相比，测量了β-sito-Alg/Ch/NPs的药代动力学参数，包括Cmax、Tmax、半衰期（t1/2）和生物利用度。在生物pH 7.4下评估了β-sito-Alg/Ch/NPs的稳定性。据报道，在pH 7.4的磷酸盐缓冲盐溶液（PBS）中，β-sito-Alg/Ch/NPs的药物释放率为41±6%，而β-sito混悬液为11±1%。在模拟肿瘤微环境的酸性pH 5.5下，β-sito-Alg/Ch/NPs的药物释放率为75±9%，而β-sito混悬液为12±4%。与β-sito混悬液相比，β-sito-Alg/Ch/NPs表现出更大的细胞毒性（p<0.05）和口服生物利用度高约3.41倍。有趣的是，这项工作表明，与β-sito混悬液相比，β-sito-Alg/Ch/NPs由于生物利用度提高和抗氧化潜力而表现出更高的细胞毒性。
