Asmawi Azren Aida, Salim Norazlinaliza, Abdulmalek Emilia, Abdul Rahman Mohd Basyaruddin
Integrated Chemical BioPhysics Research, Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, Serdang 43400, Malaysia.
UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang 43400, Malaysia.
Pharmaceutics. 2023 Feb 15;15(2):652. doi: 10.3390/pharmaceutics15020652.
Lung cancer is one of the deadliest pulmonary diseases in the world. Although docetaxel (DTX) has exhibited superior efficacy in lung cancer treatment, it has demonstrated numerous adverse effects and poor bioavailability. The natural product extract, curcumin (CCM), has reportedly reduced toxicity and synergistically improved DTX bioavailability. Nonetheless, the hydrophobic nature of DTX and CCM limits their clinical use. Nanoemulsion pulmonary delivery of DTX and CCM has demonstrated potential as a drug carrier to alleviate these drawbacks. The controlled preparation of inhalable DTX- and CCM-loaded nanoemulsions within the 100 to 200 nm range was explored in this study. A response surface methodology (RSM) based on a central composite design (CCD) was utilized to fabricate the desired size of the nanoemulsion under optimized conditions. Different process parameters were employed to control the size of the nanoemulsions procured through a high-energy emulsification technique. The size of the resultant nanoemulsions decreased with increasing energy input. The actual response according to the targeted sizes for DTX- and CCM-loaded nanoemulsion models exhibited excellent agreement with the predicted value at below 5% residual standard error under optimized conditions. The nanoemulsion of 100 nm particle size demonstrated better membrane permeability than their larger counterparts. Moreover, the formulations documented favorable physicochemical and aerodynamic pulmonary delivery properties and reduced toxicity in human lung fibroblast (MRC-5) cells. Hence, this tunable size of nanoemulsions could be a suitable alternative drug delivery for pulmonary diseases with increased local lung concentration.
肺癌是世界上最致命的肺部疾病之一。尽管多西他赛（DTX）在肺癌治疗中已显示出卓越疗效，但它也表现出许多不良反应且生物利用度低。据报道，天然产物提取物姜黄素（CCM）可降低毒性并协同提高DTX的生物利用度。尽管如此，DTX和CCM的疏水性限制了它们的临床应用。DTX和CCM的纳米乳剂肺部给药已显示出作为药物载体缓解这些缺点的潜力。本研究探索了在100至200nm范围内可吸入的负载DTX和CCM的纳米乳剂的可控制备。基于中心复合设计（CCD）的响应面方法（RSM）被用于在优化条件下制备所需尺寸的纳米乳剂。采用不同的工艺参数来控制通过高能乳化技术获得的纳米乳剂的尺寸。所得纳米乳剂的尺寸随着能量输入的增加而减小。在优化条件下，根据负载DTX和CCM的纳米乳剂模型的目标尺寸得到的实际响应与预测值在残留标准误差低于5%时表现出极好的一致性。粒径为100nm的纳米乳剂比其较大的同类产品表现出更好的膜通透性。此外，这些制剂具有良好的物理化学和空气动力学肺部给药特性，并降低了对人肺成纤维细胞（MRC-5）的毒性。因此，这种可调节尺寸的纳米乳剂可能是一种适合肺部疾病的替代药物递送方式，可提高肺部局部药物浓度。
