Rahim Muhammad Abdur, Madni Asadullah, Tahir Nayab, Jan Nasrullah, Shah Hassan, Khan Safiullah, Ullah Riaz, Bari Ahmed, Khan Muhammad Sohaib
Department of Pharmaceutics, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan.
College of Pharmacy, University of Sargodha, Sargodha 40100, Pakistan.
Pharmaceutics. 2021 Aug 21;13(8):1310. doi: 10.3390/pharmaceutics13081310.
The current study is aimed to fabricate doxorubicin (Dox) loaded mild temperature responsive liposomes (MTLs) by thin film hydration technique for enhanced in vitro and in vivo anticancer efficacy against hepatocellular carcinoma. The aforementioned Dox loaded MTLs were developed and optimized with extrusion and drug loading techniques. The optimized MTLs were in optimum size range (118.20 ± 2.81-187.13 ± 4.15 nm), colloidal stability (-13.27 ± 0.04 to -32.34 ± 0.15 mV), and enhanced entrapment of Dox (28.71 ± 2.01-79.24 ± 2.16). Furthermore, the optimized formulation (MTL1-E) embodied improved physicochemical stability deducted by Fourier transform infra-red (FTIR) spectroscopy and mild hyperthermia-based phase transition demonstrated from differential scanning calorimetry (DSC). An in vitro drug release study revealed mild hyperthermia assisted rapid in vitro Dox release from MTLs-E (T ≈ 1 h) by Korsmeyer-Peppas model based Fickian diffusion ( < 0.45). Likewise, an in vitro cytotoxicity study and lower IC values also symbolized mild hyperthermia (40.2 °C) based quick and improved cytotoxicity of MTL1-E in HepG2 and MCF-7 cells than Dox. The fluorescence microscopy also represented enhanced cellular internalization of MTL1-E at mild hyperthermia compared to the normothermia (37.2 °C). In addition, an in vivo animal study portrayed the safety, improved anticancer efficacy and healing of hepatocellular carcinoma (HCC) through MTL1-E. In brief, the Dox loaded MTLs could be utilized as safe and effective therapeutic strategy against HCC.
本研究旨在通过薄膜水化技术制备负载阿霉素（Dox）的温和温度响应脂质体（MTL），以增强其对肝癌的体外和体内抗癌疗效。上述负载Dox的MTL通过挤压和载药技术进行开发和优化。优化后的MTL具有最佳尺寸范围（118.20±2.81 - 187.13±4.15 nm）、胶体稳定性（-13.27±0.04至-32.34±0.15 mV）以及增强的Dox包封率（28.71±2.01 - 79.24±2.16）。此外，优化后的制剂（MTL1-E）通过傅里叶变换红外（FTIR）光谱显示出改善的物理化学稳定性，差示扫描量热法（DSC）证明了基于温和热疗的相变。体外药物释放研究表明，基于Korsmeyer-Peppas模型的Fickian扩散（<0.45），温和热疗可促进MTLs-E中Dox的快速体外释放（T≈1小时）。同样，体外细胞毒性研究和较低的IC值也表明，与Dox相比，温和热疗（40.2°C）可使MTL1-E在HepG2和MCF-7细胞中具有快速且增强的细胞毒性。荧光显微镜检查还显示，与正常体温（37.2°C）相比，温和热疗时MTL1-E的细胞内化增强。此外，体内动物研究表明MTL1-E对肝癌（HCC）具有安全性、改善的抗癌疗效和治愈作用。简而言之，负载Dox的MTL可作为一种安全有效的治疗肝癌的策略。
