Quantification and Brain Targeting of Eugenol-Loaded Surface Modified Nanoparticles Through Intranasal Route in the Treatment of Cerebral Ischemia

Objective To enhance brain bioavailability for intranasally administered Eugenol-encapsulated-chitosan-coated-PCL-Nanoparticles (CS-EUG-PCL-NPs). Methods Chitosan-coated-PCL-Nanoparticles (CS-PCL-NPs) were developed through double emulsification-solvent evaporation technique and further characterized for particle size, zeta potential, size distribution, encapsulation efficiency as well as in vitro drug release. UPLC-PDA method was developed to evaluate brain-drug uptake for optimized CS-EUG-PCL-NPs and to determine it's pharmacokinetic in rat's brain as well as plasma. Results Mean particles size (224.55.31), polydispersity index (PDI) i.e. (0.216 +/- 0.020) and entrapment efficiency (68.13 +/- 5.03) was determined for developed NPs. UPLC-PDA-e study showed a significantly high mucoadhesive potential of CS-EUG-PCL-NPs and least for conventional and homogenized nanoformulation; elution time for EUG and internal standard (IS) thymoquinone as 3.50 and 3.61min were observed respectively. Furthermore, intra and inter-assay (%CV) of 0.25-1.57, %accuracy (97.11-99.00%) as well as a linear dynamic range (100.00ng/mL-2500.0ng/mL), was observed. Pharmacokinetic studies in Wistar rat brain and plasma exhibited a high AUC(0-24) alongwith an amplified C-max (p**<0.01) as compared to i.v. treated group. Conclusions Intranasal administration of developed CS-coated-EUG-loaded-PCL-NPs enhanced the drug bioavailability in rat brain and thus preparation of Eugenol-NPs may help treat cerebral ischemia effectively. The toxicity studies performed at the end revealed safe nature of optimized nanoformulation.