Adediran Emmanuel, Vijayanand Sharon, Kale Akanksha, Gulani Mahek, Wong Jennifer C, Escayg Andrew, Murnane Kevin S, D'Souza Martin J
Nanotechnology Laboratory, Center for Drug Delivery Research, College of Pharmacy, Mercer University, Atlanta, GA 30341, USA.
Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.
Pharmaceutics. 2025 Apr 1;17(4):452. doi: 10.3390/pharmaceutics17040452.
The neuropeptide oxytocin has been identified as a potential therapeutic molecule. However, the therapeutic potential of this molecule is limited due to the challenges faced in oxytocin delivery to the brain. Scientific innovation has led to the breakthrough discovery of many modalities to encapsulate molecules for targeted drug delivery, which can enhance oxytocin delivery to the brain. This research aimed to explore a microfluidics-based system that optimizes the formulation of cross-linked bovine serum albumin (BSA) nanoparticles encapsulating oxytocin. : First, the formulation parameters were optimized using a design of experiments (DOE) by evaluating the effect of flow rate, polymer concentration, and the binary solvent mixture polarity on the nanoparticle size. Drug encapsulation efficiency, release, and kinetics profile were characterized. These oxytocin nanoparticles were conjugated to rabies virus glycoprotein (RVG), a brain-targeting ligand, and the conjugation efficiency was determined. : The sizes of the nanoparticles were between 50 nm and 75 nm with a <0.4 polydispersity index. The encapsulation efficiency was >80%. Approximately 58% of oxytocin was released from the nanoparticles within the first six hours, showing an initial burst that is ideal for seizure control and thereafter exhibiting the Korsmeyer-Peppas release kinetics. : For the first time, we demonstrated the microfluidics method of formulating nanoparticles with particle size of less than 100 nm, with improved encapsulation efficiency and optimal release profile for oxytocin brain delivery.
神经肽催产素已被确定为一种潜在的治疗分子。然而，由于在将催产素输送到大脑过程中面临的挑战，该分子的治疗潜力受到限制。科学创新带来了许多用于封装分子以实现靶向药物递送的方式的突破性发现，这可以提高催产素向大脑的递送。本研究旨在探索一种基于微流体的系统，该系统可优化包裹催产素的交联牛血清白蛋白（BSA）纳米颗粒的配方。首先，通过评估流速、聚合物浓度和二元溶剂混合物极性对纳米颗粒大小的影响，使用实验设计（DOE）优化配方参数。对药物包封效率、释放和动力学曲线进行了表征。将这些催产素纳米颗粒与脑靶向配体狂犬病病毒糖蛋白（RVG）偶联，并测定偶联效率。纳米颗粒的大小在50纳米至75纳米之间，多分散指数<0.4。包封效率>80%。在最初的六个小时内，约58%的催产素从纳米颗粒中释放出来，显示出对癫痫控制理想的初始突释，此后呈现出 Korsmeyer-Peppas 释放动力学。我们首次展示了一种微流体方法，可制备粒径小于100纳米的纳米颗粒，具有提高的包封效率和用于催产素脑递送的最佳释放曲线。
