Quality by design-based development of transferrin-functionalized nanostructured lipid carriers for targeted Co-delivery of ropinirole and mangiferin for improved drug-delivery to the brain.

Ischemic stroke (IS) persists as a major contributor of mortality and functional impairment globally, because of limited conventional drug delivery system and restrictive properties of the blood-brain barrier (BBB). In recent years, Ligand-conjugated nanomaterial-based drug delivery systems have emerged as effective techniques to improve brain-targeted therapy through multimodal approach. In this context, the present study proposes an innovative nanotechnology based Transferrin (Tf)-conjugated Nanostructured Lipid carrier (NLC) co-loaded Ropinirole (RP), and Mangiferin (MF) to facilitate targeted and effective delivery across the BBB. The characterization of developed Transferrin-conjugated Ropinirole-Mangiferin-Nanostructured Lipid carrier (Tf-RP-MF-NLC) demonstrated a mean particle size of 163.9 ± 2.97 nm, a polydispersity index (PDI) of 0.31 ± 0.04, zeta potential of -8.589 ± 3.63 mV and spherical morphology as shown by Transmission Electron Microscopy (TEM) Analysis. The entrapment efficiency (EE) of RP and MF was found to be >85%, while Tf conjugation efficiency was estimated to be >60%. The % cumulative drug release was found to be >80% for RP and > 65% for MF over 24 h from Tf-RP-MF-NLC. The antioxidant effect and biocompatibility of the Tf-RP-MF-NLC were confirmed by the DPPH assay and haemolysis testing, respectively. Furthermore, results obtained from gamma scintigraphy study revealed that Tf-RP-MF-NLC had enhanced brain targeting and increased drug accumulation as compared to RP-MF-NLC following intraperitoneal (i.p.) administration. Overall, these findings highlights Tf-RP-MF-NLC as a promising brain targeted nanocarrier system with improved drug delivery, suggesting its potential as an effective therapeutic strategy for improved drug delivery to the brain.