Nanobiofar Group, Department of Pharmacology, Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Santiago de Compostela, Campus Vida, E-15782-Santiago de Compostela, Spain.
Colloids and Polymers Physics Group, Department of Condensed Matter Physics, Faculty of Physics, University of Santiago de Compostela, Campus Vida, E-15782-Santiago de Compostela, Spain.
Int J Pharm. 2018 Nov 15;551(1-2):23-33. doi: 10.1016/j.ijpharm.2018.08.049. Epub 2018 Aug 25.
Combined micro- and nanosystems are appealing for pulmonary protein delivery, fulfilling the specific physiological requirements for efficient outcomes in-vivo. However, fabrication of protein formulations may impose stresses perturbing protein conformational stability and, hence, biological activity. Herein, a protein, insulin (INS), was nanoencapsulated inside chitosan nanoparticles (CS NPs) by ionic gelation. By spray drying, the resultant protein-loaded NPs were further encapsulated with a thermoprotectant into powders bearing adequate aerodynamic properties for lung delivery. Structural modifications and interactions of the protein/carrier system were investigated following processing, with special emphasis on protein integrity. Accordingly, physicochemical, elemental, structural and thermal experiments were performed. The analyses revealed the localization of a proportion of the protein on the NPs' surface following nanoencapsulation, and the involved molecular interactions between the NPs and thermoprotectant after microencapsulation. Protein integrity was conserved throughout the preparation processes. This highlights the non-invasiveness of the fabrication techniques, particularly spray drying, for preparing micro-nanosystems for effective administration of inhalable macromolecules.
组合式微纳系统在肺部蛋白传递中具有吸引力，满足了体内高效结果的特定生理需求。然而，蛋白质制剂的制备可能会对蛋白质构象稳定性产生影响，从而影响其生物活性。在此，通过离子凝胶法将蛋白质胰岛素（INS）纳米封装到壳聚糖纳米颗粒（CS NPs）中。通过喷雾干燥，将所得的载蛋白 NPs 进一步用热保护剂包封到粉末中，这些粉末具有足够的空气动力学特性，可用于肺部给药。在加工过程中研究了蛋白质/载体系统的结构修饰和相互作用，特别强调了蛋白质的完整性。因此，进行了物理化学、元素、结构和热实验。分析表明，纳米包封后，一部分蛋白质定位于 NPs 的表面，微包封后 NPs 与热保护剂之间存在分子相互作用。在整个制备过程中保持了蛋白质的完整性。这突出了制备技术的非侵入性，特别是喷雾干燥技术，用于制备用于有效施用以吸入为途径的大分子的微纳米系统。
