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.

Purpose: This study aimed to develop spanlastics-loaded buccal films to overcome the oral bioavailability limitations of olmesartan medoxomil (OLM), a sparsely water-soluble antihypertensive agent. Methods: OLM-loaded spanlastics were prepared using the ethanol injection method. A 2 ⁴ factorial design was employed to investigate the effects of different variables on vesicles’ features and to identify the optimized spanlastic formula (OS). Vesicles were characterized in terms of entrapment efficiency (EE), particle size (PS), zeta potential (ZP), and polydispersity index (PDI). OS was further characterized in vitro, incorporated into buccal films, and its pharmacodynamic performance was assessed in a single-dose study in hypertensive rats, compared to orally administered OLM suspension. Results: OS showed spherical vesicles with EE% of 67.7±2.97%, PS of 202.6±4.38 nm, ZP of ‒32.00±1.27 mV, and PDI of 0.272±0.00. OS showed markedly higher OLM release over 24 h compared to OLM suspension. Differential scanning calorimetry indicated drug amorphization. In vitro characterization, along with histopathological examination, demonstrated that OS-loaded films were well-tolerated and safe for buccal administration. Furthermore, pharmacodynamic evaluation revealed that these films significantly enhanced and sustained the antihypertensive effect of OLM, achieving a 1.68-fold increase in area under the antihypertensive effect-time curve and a 1.67-fold prolongation in effect half-life. Conclusion: These findings confirm the enhanced and sustained antihypertensive effect of OLM delivered via spanlastics-loaded buccal films, highlighting them as a promising delivery system for OLM.