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

Abstract

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.

Preparation, Characterization, and In Vivo Pharmacokinetic Evaluation of Polyvinyl Alcohol and Polyvinyl Pyrrolidone Blended Hydrogels for Transdermal Delivery of Donepezil HCl

“…These results were in accordance with the observation of previously obtained results [26,39,40]. Harthi et al recently studied the gelation behavior of PVP hydrogels with different contents of polyethylene glycol (PEG) and found that the gel fraction (%) was reduced as the concentration of PEG increased, while the gel fraction (%) was maximum at 0% PEG content (PVP hydrogel without PEG content) [26]. In addition, the gelation behavior of PVA hydrogel was maximal, almost 90%, in the absence of sodium alginate (SA) and decreased with the increasing content of SA, i.e., a 27% gel fraction at 30% SA [39].…”

“…Consequently, the cross-linking network chains are reduced by reducing physical interactions between the PVA and PVP network and, thus decreased the gelation process. These results were in accordance with the observation of previously obtained results [26,39,40]. Harthi et al recently studied the gelation behavior of PVP hydrogels with different contents of polyethylene glycol (PEG) and found that the gel fraction (%) was reduced as the concentration of PEG increased, while the gel fraction (%) was maximum at 0% PEG content (PVP hydrogel without PEG content) [26].…”

“…However, the addition of cosolvent will reduces the cross-linking density and network formation resulting in the enhanced elasticity and flexibility of hydrogels. Moreover, cosolvent will engross the water molecules from the release medium, and increases the solubilization of the drug, leading to decreasing the viscosity of the hydrogels and increasing the release rate of the drug [26]. These PVA-PVP blended hydrogels have improved water uptake capacity, possess high elasticity and soft consistency, are pleasant to touch, terminate easily without pain, and have mechanical strength and transparency [27].…”

“…After 24 h, dried hydrogel samples were immersed in 1000 mL distilled water for 24 h to reach equilibrium swelling and to remove the soluble parts. Subsequently, the samples were dried again in an oven at 50 • C (W e ) for 24 h [26]. The gel fraction was calculated as follows:…”

“…To measure water uptake capacity, circular hydrogel samples (2 cm diameter and 2 mm thickness) were prepared and dried in an oven at 50 • C for 24 h. Then the weights of dried hydrogels (W e ) were measured immediately. Subsequently, samples were immersed in distilled water at 37 • C for 24 h. Finally, the weight of the soaked hydrogel samples was measured (W s ) [26]. The swelling ratio was calculated as follows:…”