Comparative Study of Donepezil-Loaded Formulations for the Treatment of Alzheimer’s Disease by Nasal Administration

Abstract

Alzheimer’s disease is characterized by a progressive deterioration of neurons resulting in a steady loss of cognitive functions and memory. Many treatments encounter the challenge of overcoming the blood–brain barrier, thus the intranasal route is a non-invasive effective alternative that enhances the drug delivery in the target organ–the brain–and reduces the side effects associated with systemic administration. This study aimed at developing intranasal gels of donepezil as an approach to Alzheimer’s disease. Three different gels were elaborated and characterized in terms of pH, morphology, gelation temperature, rheology, and swelling. An in vitro release study and an ex vivo permeation in porcine nasal mucosa were conducted on Franz diffusion cells. The tolerability of the formulations was determined by the cytotoxicity in human nasal cells RPMI 2650. Results showed that pluronic gels exhibit the higher release rate and enhanced permeation compared to chitosan gel. Moreover, the combination of Pluronic F-127 and Transcutol® P exerted a synergic effect on the permeation of donepezil through the nasal mucosa. The resulting gels showed suitable tolerance in the RPMI 2650 cell line and physicochemical characteristics for intranasal delivery, and thus gel formulations administered by nasal mucosa could be an alternative strategy to improve the bioavailability of donepezil.

A Novel Approach for Dermal Application of Pranoprofen-Loaded Lipid Nanoparticles for the Treatment of Post-Tattoo Inflammatory Reactions

“…PRA released from the nanostructure lipid carrier followed a first-order kinetic model with a constant (Kf) of 0.031 ± 0.005 h −1 ; the constant corresponds to the release rate at which the drug is released from the formulation, and higher Kf values represent faster drug release. The first-order model assumes that the release rate is directly correlated to the amount of drug remaining in the formulation; that is, the drug release rate decreases over time [60,61]. This profile can be seen in Figure 5, in which after 48 h, the diffusion of the drug through the dialysis membrane was minimal.…”

Chitosan-Based Thermogelling System for Nose-to-Brain Donepezil Delivery: Optimising Formulation Properties and Nasal Deposition Profile

“…Donepezil oral delivery has several limitations including first-pass metabolism, gastrointestinal and peripheral adverse effects, and low brain bioavailability [ 17 ]. On the contrary, the nasal administration of donepezil offers the potential for its efficient and direct central nervous system delivery, reduced systemic bioavailability, and a lower risk of adverse effects [ 18 ]. The recognised advantages of nasal donepezil delivery have led to the development of several liquid pharmaceutical platforms including donepezil nanosuspension [ 19 ], donepezil-loaded liposomes [ 20 , 21 ], nanoemulsion [ 22 ], lipid nanoparticles [ 23 ], microemulsion [ 24 ], and in situ gel [ 17 ], improving donepezil solubility and/or its permeation profile and enhancing its brain bioavailability, as evidenced in animal models in vivo.…”

Gel Formulations with an Echinocandin for Cutaneous Candidiasis: The Influence of Azone and Transcutol on Biopharmaceutical Features

“…Figure8shows the rheograms of CPF-gel and CPF-AZ-gel at 10, 25, and 32 • C. Rheological behavior plays a critical role in topical formulations, as it determines sensory and dosage characteristics, as well as modulates the biopharmaceutical parameters, such as the drug release rate from its vehicle[37]. CPF-AZ-gel exhibited a higher viscosity than CPF-gel due to its Azone and Transcutol-P content, providing greater consistency to the final product.…”