Comparative in-vivo and in-vitro characterization of Donepezil loaded Lactoferrin linked PEG coated and uncoated nanocarriers as intranasal drug delivery system.

Alzheimer's disease treatment faces challenges with conventional oral formulations of donepezil (DNP). This study aims to develop and characterize DNP-loaded Lactoferrin (LCF)-linked PEG-coated nano-carriers for intranasal delivery. The formulation was developed using a Quality by Design (QbD) approach integrated with molecular docking. A novel micelle-enhanced spectrofluorimetric method was developed and validated for in-vitro and in-vivo characterization of the nano-carriers. The method was optimized using Analytical Quality by Design (AQbD) principles. In-vivo pharmacokinetic and bio-distribution studies were conducted in rats to compare the developed formulation with uncoated NLCs and conventional dosage forms. The LCF-PEG-coated NLCs showed improved brain targeting efficiency compared to uncoated NLCs and conventional formulations. The spectrofluorimetric method demonstrated high sensitivity and reliability for both in-vitro and in-vivo analyses. The developed DNP-loaded LCF-PEG-coated NLCs show promise as an effective intranasal delivery system for Alzheimer's disease treatment. The novel spectrofluorimetric method offers a sustainable and efficient alternative to conventional LC-MS/MS techniques for characterizing DNP formulations.