Title : Evaluation of surface-charged donepezil-loaded liposomes for intranasal nose-to-brain drug delivery
Abstract:
Intranasal drug administration has gained considerable attention as a non-invasive approach for delivering therapeutic agents directly to the central nervous system (CNS). This route provides the potential to bypass the blood–brain barrier and improve drug targeting to the brain. However, limited permeability of many drugs across the nasal mucosa remains a significant challenge. Nanocarrier systems, particularly liposomes, have emerged as promising drug delivery platforms due to their biocompatibility, structural versatility, and ability to enhance drug transport across biological barriers.
The aim of this study was to develop and evaluate oppositely charged liposomal formulations containing donepezil hydrochloride (DPZ) for potential intranasal drug delivery. Liposomes were prepared using the thin-film hydration method followed by probe sonication to obtain nanosized vesicles. Phosphatidylcholine and cholesterol served as the main lipid components, while dicetyl phosphate (DCP) and stearylamine (SA) were used as charge-inducing agents to produce negatively and positively charged liposomes, respectively.
The prepared formulations were characterized for vesicle size, polydispersity index, zeta potential, and encapsulation efficiency using dynamic light scattering and UV–visible spectrophotometry. Furthermore, in vitro drug release, permeability across a synthetic nasal membrane, and mucoadhesive behavior were investigated to determine the suitability of the formulations for intranasal delivery.
The results demonstrated that the incorporation of DCP reduced vesicle size and promoted faster drug release, whereas SA increased vesicle size and improved mucoadhesive properties. Both negatively and positively charged liposomes exhibited enhanced encapsulation efficiency compared to the non-modified formulation. Additionally, DCP-containing liposomes showed improved permeability across the nasal membrane, while SA-modified formulations displayed stronger mucoadhesion, which may contribute to prolonged nasal residence time.
These findings suggest that modifying the surface charge of liposomal carriers can significantly influence their physicochemical characteristics and delivery performance. Oppositely charged liposomal systems represent a promising strategy for enhancing the intranasal delivery of donepezil and may support the development of effective nose-to-brain drug delivery systems for neurological disorders.
