Nanocarriers (synthetic/cell-based have attracted enormous interest for various therapeutic indications, including neurodegenerative disorders. A broader understanding of the impact of nanomedicines design is now required to enhance their translational potential. Nanoformulations in vivo journey is significantly affected by their physicochemical properties including the size, shape, hydrophobicity, elasticity, and surface charge/chemistry/morphology, which play a role as an interface with the biological environment. Understanding protein corona formation is crucial in characterizing nanocarriers and evaluating their interactions with biological systems. In this review, the types and properties of the brain-targeted nanocarriers are discussed. The biological factors and nanocarriers properties affecting their in vivo behavior are elaborated. The compositional description of cell culture and biological matrices, including proteins potentially relevant to protein corona built-up on nanoformulation especially for brain administration, is provided. Analytical techniques of characterizing nanocarriers in complex matrices, their advantages, limitations, and implementation challenges in industrial GMP environment are discussed. The uses of orthogonal complementary characterization approaches of nanocarriers are also covered.

纳米载体（基于合成/细胞的载体已引起人们对各种治疗适应症的极大兴趣，包括神经退行性疾病。现在需要对纳米药物设计的影响有更广泛的了解，以增强它们的翻译潜力。纳米制剂在体内的旅程受到其理化特性的显着影响，包括大小，形状，疏水性，弹性和表面电荷/化学/形态，它们与生物环境有关。了解蛋白质电晕的形成对于表征纳米载体并评估其与生物系统的相互作用至关重要。讨论了以脑为靶点的纳米载体的类型和性质，影响它们的生物学因素和纳米载体的性质详细阐述了体内行为。提供了细胞培养物和生物基质的组成描述，包括与可能在纳米制剂上积累的蛋白质电晕有关的蛋白质，尤其是对于大脑给药。讨论了表征复杂基质中纳米载体的分析技术，其优势，局限性以及在工业GMP环境中的实施挑战。还涵盖了纳米载体正交互补表征方法的使用。