Prasanthan Pooja, Kishore Nand
Department of Chemistry, Indian Institute of Technology Bombay Powai Mumbai 400 076 India
RSC Adv. 2021 Jun 22;11(36):22057-22069. doi: 10.1039/d1ra03770f. eCollection 2021 Jun 21.
Micelles formed by pluronic triblock copolymers are known to be a promising class of drug delivery vehicles. Quantitative mechanistic insights into the ability of pluronic micelles to improve the solubility of poorly water soluble drugs, encapsulation and delivery of hydrophilic drugs are not available. The current study evaluated the energetics of encapsulation of chemotherapeutic drugs gemcitabine, cytarabine, and hydroxyurea in pluronic F127 and F68 micelles. In addition, the interactions of the drugs released from pluronic micellar media with serum albumin, which is a major circulatory transport protein, and subsequent conformational changes have also been analyzed with the help of calorimetry and spectroscopy. All the drugs showed improved partitioning in F127 micelles, the extent of which slightly increased with temperature rise. Interestingly, drug-protein binding is enhanced upon delivery from pluronic micelles without affecting the conformational integrity of the protein. This study highlights the role of drug functionalities, hydrophobicity, and steric factors towards their partitioning in pluronic micelles. Such studies are important in understanding physicochemical aspects of drug encapsulation and release, and lead to establishing structure-property-energetics correlations for developing suitable nano-drug delivery vehicles.
已知由普朗尼克三嵌段共聚物形成的胶束是一类很有前景的药物递送载体。目前尚缺乏关于普朗尼克胶束提高难溶性药物溶解度、包封及递送亲水性药物能力的定量机制见解。本研究评估了化疗药物吉西他滨、阿糖胞苷和羟基脲在普朗尼克F127和F68胶束中的包封能量学。此外，还借助量热法和光谱法分析了从普朗尼克胶束介质中释放的药物与血清白蛋白（一种主要的循环转运蛋白）的相互作用以及随后的构象变化。所有药物在F127胶束中的分配情况均有所改善，且随着温度升高，改善程度略有增加。有趣的是，从普朗尼克胶束递送药物后，药物与蛋白质的结合增强，而不影响蛋白质的构象完整性。本研究强调了药物官能团、疏水性和空间因素在其在普朗尼克胶束中分配方面的作用。此类研究对于理解药物包封和释放的物理化学方面很重要，并有助于建立结构-性质-能量学相关性，以开发合适的纳米药物递送载体。
