Development and evaluation of protamine-coated PLGA nanoparticles for nose-to-brain delivery of tacrine: In-vitro and in-vivo assessment

The present study aimed for the development and in-vitro/in-vivo evaluation of tacrine loaded poly-(D,l)-lactide-co-glycolide nanoparticles (TCR-PLGA NPs) for the treatment of Alzheimer's disease. TCR-loaded PLGA NPs were prepared using nanoprecipitation technique and formulation parameters (i.e. surfactant type, MW of polymer (PLGA) and drug to polymer ratio) were evaluated by the factorial design analysis. The optimal formulae were surface modified with protamine sulphate (Pt) to improve their brain targeting via intranasal administration. The produced NPs were small in size (70.55–237.67 nm) with low polydispersity index (0.075–0.224) and adequate TCR entrapment efficiency within the range of 4.35–33.78%. The in-vitro degradation of the selected formulae followed the first-order kinetics and was related with the in-vitro release study which followed a sustained release pattern with a maximum release of up to 43.65% within 120 h. The in-vivo study demonstrated a good brain targeting efficiency after intranasal administration of Pt-coated PLGA NPs in the form of nanocomposite gel in carbopol 934 to rats, in comparison with uncoated NPs, where the Pt-coated NPs have demonstrated higher brain absolute bioavailability of TCR (265.24 ± 62.99%). The histopathological examination revealed the safety of the intranasal nanocomposite gel of Pt-coated PLGA NPs.