Nasal delivery of donepezil HCl-loaded hydrogels for the treatment of Alzheimer’s disease

• Published in: Scientific reports 2019-07, Vol.9 (1), p.9563-20, Article 9563
• Main Authors: Al Harthi, Sitah, Alavi, Seyed Ebrahim, Radwan, Mahasen Ali, El Khatib, Mona Mohamed, AlSarra, Ibrahim Abdullah
• Format: Article
• Language: English
• Subjects: 631/61/54/152; 631/92/152; Administration, Intranasal; Alzheimer Disease - drug therapy; Animals; Biological Availability; Chitosan; Cholinesterase Inhibitors - administration & dosage; Cholinesterase Inhibitors - chemistry; Cholinesterase Inhibitors - pharmacokinetics; Dialysis; Donepezil; Donepezil - administration & dosage; Donepezil - chemistry; Donepezil - pharmacokinetics; Drug Liberation; Drug Monitoring; Drug Stability; Evaporation; Humanities and Social Sciences; Hydrogels; Hydrogels - chemistry; Kinetics; Liposomes; Liposomes - chemistry; Liposomes - ultrastructure; Liquid chromatography; multidisciplinary; Pharmacokinetics; Rabbits; Rheology; Scanning electron microscopy; Science; Science (multidisciplinary); Tablets
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-46032-y

This study aims to prepare, characterize and evaluate the pharmacokinetics of liposomal donepezil HCl (LDH) dispersed into thiolated chitosan hydrogel (TCH) in rabbits. Various hydrogels including TCH were prepared, and after characterization, TCH was selected for subsequent evaluations, due to the promising results. TCH was then incorporated with LDH prepared by reverse phase evaporation method. The hydrogel was characterized using scanning electron microscope, dialysis membrane technique, and ultra-performance liquid chromatography methods. The optimized resultant was then evaluated in terms of pharmacokinetics in an in vivo environment. The mean size of LDH and drug entrapment efficiency were 438.7 ± 28.3 nm and 62.5% ± 0.6, respectively. The controlled drug release pattern results showed that the half-life of the loaded drug was approximately 3.5 h. Liposomal hydrogel and free liposomes were more stable at 4 °C compared to those in 20 °C. The pharmacokinetics study in the rabbit showed that the optimized hydrogel increased the mean peak drug concentration and area under the curve by 46% and 39%, respectively, through nasal route compared to the oral tablets of DH. Moreover, intranasal delivery of DH through liposomal hydrogel increased the mean brain content of the drug by 107% compared to the oral DH tablets. The results suggested that liposomes dispersed into TCH is a promising device for the nasal delivery of DH and can be considered for the treatment of Alzheimer’s disease.