Intranasal Delivery of Paclitaxel-Loaded Ligand Conjugated Polymeric Nanoparticles for Targeted Brain Delivery

Abstract

Compared to the conventional blood–brain barrier crossing over, nose-to-brain delivery provides a potentially effective substitution, particularly when large molecules of drugs need to be delivered. The majority of macromolecules degrade quickly in a physiological environment. Therefore, drug molecules can be protected against early breakdown by using nanocarrier systems. Targeting nanocarrier system with ligand potential of enhancing bioavailability due to tailored binding affinity to targeting site. In the current study, we prepared paclitaxel (PTX) loaded ascorbic acid (AA) conjugated polycaprolactone (PCL) nanoparticles (NPs) for intranasal administration. Polymeric nanoparticles (PNPs) were prepared using the solvent evaporation method, which was further analyzed for particle size, polydispersity index (PDI), surface charge, encapsulation-efficiency (EE), drug loading (DL), surface morphology, in-vitro drug release, and in-vivo pharmacokinetic evaluation. Results showed the optimized PTX-PNPs showed particle size 114.7 ± 2.96 nm, zeta potential -27.6 ± 1.63 mV, with entrapment efficiency 97.3 ± 0.41%, and drug loading 35.3 ± 0.38%. In-vitro PTX release showed a biphasic release pattern, primary burst release followed by sustained release was observed. An in-vivo pharmacokinetic study showed a 5.6-fold increase in the PTX concentration reaching to the brain. Histopathological results of the nasal mucosa showed minimal alteration after 72 h of administering surface-modified paclitaxel loaded polymeric nanoparticles (AA-PTX-PNPs). Thus, this study highlighted the suitability of a AA-PTX-PNPs as a promising strategy for intranasal administration therapy for various brain disorders.

Graphical Abstract