Department of Molecular and Cellular Biosciences, Rowan University, 201 Mullica Hill Rd., Glassboro, NJ 08028, USA.
Department of Physics & Astronomy, Rowan University, 201 Mullica Hill Rd., Glassboro, NJ 08028, USA.
Molecules. 2022 Feb 27;27(5):1572. doi: 10.3390/molecules27051572.
Despite considerable advances in recent years, challenges in delivery and storage of biological drugs persist and may delay or prohibit their clinical application. Though nanoparticle-based approaches for small molecule drug encapsulation are mature, encapsulation of proteins remains problematic due to destabilization of the protein. Reverse micelles composed of decylmonoacyl glycerol (10MAG) and lauryldimethylamino-N-oxide (LDAO) in low-viscosity alkanes have been shown to preserve the structure and stability of a wide range of biological macromolecules. Here, we present a first step on developing this system as a future platform for storage and delivery of biological drugs by replacing the non-biocompatible alkane solvent with solvents currently used in small molecule delivery systems. Using a novel screening approach, we performed a comprehensive evaluation of the 10MAG/LDAO system using two preparation methods across seven biocompatible solvents with analysis of toxicity and encapsulation efficiency for each solvent. By using an inexpensive hydrophilic small molecule to test a wide range of conditions, we identify optimal solvent properties for further development. We validate the predictions from this screen with preliminary protein encapsulation tests. The insight provided lays the foundation for further development of this system toward long-term room-temperature storage of biologics or toward water-in-oil-in-water biologic delivery systems.
尽管近年来取得了相当大的进展，但生物药物的输送和储存仍然存在挑战，这可能会延迟或阻止它们的临床应用。虽然基于纳米颗粒的小分子药物包封方法已经成熟，但由于蛋白质的不稳定性，蛋白质的包封仍然存在问题。由癸基单酰基甘油（10MAG）和十二烷基二甲基氧化胺（LDAO）组成的反胶束在低粘度烷烃中已被证明可以保持广泛的生物大分子的结构和稳定性。在这里，我们通过用目前用于小分子输送系统的溶剂替代非生物相容性烷烃溶剂，作为生物药物储存和输送的未来平台，介绍了开发该系统的第一步。使用一种新的筛选方法，我们使用两种制备方法，在七种生物相容性溶剂中对 10MAG/LDAO 系统进行了全面评估，分析了每种溶剂的毒性和包封效率。通过使用一种廉价的亲水性小分子来测试广泛的条件，我们确定了进一步开发的最佳溶剂性质。我们用初步的蛋白质包封测试验证了该筛选的预测。该研究为进一步开发该系统以实现生物制剂的长期室温储存或水包油包水生物传递系统奠定了基础。
