Intranasal Delivery of PEGylated Mesoporous Silica Nanoparticles for Enhanced Brain Targeting: In Vivo Evaluation of Pharmacokinetics, Biodistribution and Biocompatibility

Effective treatment of neurological disorders remains challenging due to the restrictive blood–brain barrier (BBB), which limits therapeutic delivery to the central nervous system (CNS). This study presents a novel PEGylated mesoporous silica nanoparticle (MSNP) platform designed to enhance drug transport across the BBB. Curcumin, a neuroprotective compound with poor solubility and bioavailability, was encapsulated to evaluate the nanocarrier’s brain-targeting efficiency. The PEGylated curcumin-loaded MSNPs (P@CurMSNPs) were synthesized and characterized to confirm their physicochemical suitability for CNS delivery. In vivo experiments in mice demonstrated that the formulation effectively crossed the BBB after intranasal, intravenous, and intraperitoneal administration, with the intranasal route achieving the highest brain uptake within 30 minutes. Compared with free curcumin, P@CurMSNPs showed a threefold increase in peak brain concentration, approximately 15-fold higher total brain exposure (AUC), and extended retention up to 168 hours versus 6 hours for the free drug. The intrinsic fluorescence of curcumin enabled real-time tracking, while histopathological and biochemical analyses confirmed biocompatibility. This work highlights a promising non-invasive nanoplatform integrating PEGylation, mesoporous silica architecture, and intranasal delivery to overcome BBB limitations and achieve sustained brain retention with minimal systemic toxicity.