Quality by design for the synthesis and optimisation of arginine-poly (ester-amide) nanocapsules as promising carriers for nose-brain delivery of carbamazepine

Polymeric nanocapsules for direct brain drug delivery through intranasal is a promising route for drugs that need to reach the brain directly with rapid onset of action and high bioavailability. In this study, arginine-poly(esteramide) nanocapsules loaded with carbamazepine (CBZ) [(CBZ/Arg-PEA)NCs] were synthesised for direct brain delivery of CBZ via the nose-brain transport pathway using interfacial polycondensation method. Process optimisation was conducted using Quality by Design (QbD) to produce NCs with critical quality attributes (high entrapment and loading efficiencies, low particle size and extended release over 24 h). The design of experiment (DoE) entailed three critical input parameters (CBZ concentration, aqueous, and organic phases volume). The findings of the present study revealed that the optimum formulation would produce high entrapment efficiency (98.6%) and good loading efficiency (20%), targeted release (79% after 24 h) and a small particle size (400 nm). Molecular profiling using FTIR, XRD and DSC showed the formation of the polymer and its semicrystalline nature. TEM images revealed spherical NCs. In-vivo study in mice revealed that nose-brain treatment with nanocapsules was capable to deliver CBZ directly to the brain and obtained a sustained increase in brain concentration at 2, 5, and 10 min after the treatment. In conclusion, (CBZ/Arg-PEA) NCs are a promising drug brain delivery system for treating epilepsy via the nose-brain transport pathway.

Automated summary

This study developed arginine-poly(esteramide) nanocapsules loaded with carbamazepine for direct brain drug delivery via the nose-brain transport pathway. The optimized formulation showed high entrapment efficiency, good loading efficiency, targeted release, and small particle size. In vivo study demonstrated the effective delivery of CBZ to the brain through nose-brain treatment.