Abstract
To enhance brain bioavailability for intranasally administered Eugenol-encapsulated-chitosan-coated-PCL-Nanoparticles (CS-EUG-PCL-NPs). 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. Mean particles size (224.5±5.31), polydispersity index (PDI) i. e. (0.216±0.020) and entrapment efficiency (68.13±5.03) was determined for developed NPs. UPLC-PDA-eλ 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 3.61 min 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 (100.00 ng/mL-2500.0 ng/mL), was observed. Pharmacokinetic studies in Wistar rat brain and plasma exhibited a high AUC0-24 alongwith an amplified Cmax (p**<0.01) as compared to i. v. treated group. 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.
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