Polymeric nanoparticles for efficient nose-to-brain delivery.

Brain disorders affect over one billion people globally, presenting significant challenges for effective treatment due to the limited drug bioavailability in the brain. This issue is largely attributed to the presence of the blood-brain barrier (BBB), a highly selective and restrictive biological barrier. Nose-to-brain delivery (NtBD) via intranasal administration has emerged as a compelling and non-invasive strategy to bypass the BBB, leveraging the anatomical and physiological characteristics of the nasal cavity to enable direct drug transport to the brain. Among the various delivery strategies, nanoparticles, and polymeric nanoparticles in particular, stand out due to their growing attention, offering biocompatibility, biodegradability, and customizable designs. This review explores the key physicochemical characteristics of polymeric nanoparticles, including size, charge, and surface modifications, and analyses their impact on mucosal adhesion, mucopenetration, and brain targeting efficiency by crossing different biological barriers. Functionalization strategies, such as mucoadhesive coatings, cell-penetrating peptides, and targeting ligands, are discussed comprehensively to enhance drug stability, residence time, and cellular uptake. Evaluation techniques covering in vitro, ex vivo, and in vivo models are critically reviewed, emphasizing their relevance for elucidating transport mechanisms and assessing the therapeutic potential of nanoparticles. Special focus is given to the applications of polymeric nanoparticles in treating several brain diseases, where they show promising potential in optimizing drug delivery efficiency and therapeutic outcomes. By synthesizing current advancements, this review offers a robust framework for the rational development of next-generation polymeric nanoparticles tailored to advanced NtBD systems.