Development of a Nasal Donepezil-loaded Microemulsion for the Treatment of Alzheimer’s Disease: in vitro and ex vivo Characterization

2018 ◽  
Vol 17 (1) ◽  
pp. 43-53 ◽  
Author(s):  
Lupe C. Espinoza ◽  
Marisol Vacacela ◽  
Beatriz Clares ◽  
Maria Luisa Garcia ◽  
Maria-Jose Fabrega ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Acetylcholinesterase Inhibitor ◽  
In Vitro Release ◽  
Nasal Irritation ◽  
Ex Vivo Permeation ◽  
Optical Stability

Background: Donepezil (DPZ) is widely prescribed as a specific and reversible acetylcholinesterase inhibitor for the symptomatic treatment of mild to moderate Alzheimer's disease (AD). Objective: Considering the therapeutic potential of DPZ and the advantages offered by the intranasal route as an alternative for drug administration, the aim of this study was the development and characterization of a DPZ microemulsion (ME) for nose-to-brain delivery. Method: The ME was developed by construction of pseudoternary phase diagrams and characterized by dynamic light scattering and transmission electron microscopy. Flow properties and viscosity, as well as optical stability and stability under storage at different temperatures were evaluated. Finally, in vitro release and ex vivo permeation studies through porcine nasal mucosa were accomplished. Results: A transparent and homogeneous DPZ-ME (12.5 mg/ml) was obtained. The pH and viscosity were 6.38 and 44.69 mPa·s, respectively, indicating nasal irritation prevention and low viscosity. The mean droplet size was 58.9±3.2 nm with a polydispersity index of 0.19±0.04. The morphological analysis revealed the spherical shape of droplets, as well as their smooth and regular surface. Optical stability evidenced no destabilization processes. DPZ release profile indicated that the ME followed a hyperbolic kinetic model while the ex vivo permeation profile showed that the highest permeation occurred during initial 4 h and the maximum permeated amount was approximately 2000 µg, which corresponds to 80% of the starting amount of drug. Conclusion: We conclude that our nasal ME could be considered as a new potential tool for further investigation in the AD.

Synthesis of a Novel Curcumin Derivative as a Potential Imaging Probe in Alzheimer’s Disease Imaging

2019 ◽  
Vol 16 (8) ◽  
pp. 723-731 ◽  
Author(s):  
Alexander Sturzu ◽  
Sumbla Sheikh ◽  
Hubert Kalbacher ◽  
Thomas Nägele ◽  
Christopher Weidenmaier ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Flow Cytometry ◽  
Transgenic Mice ◽  
Ex Vivo ◽  
Amyloid Plaques ◽  
Laser Scanning Microscopy ◽  
Β Amyloid ◽  
Curcumin Derivative

Background: Curcumin has been of interest in the field of Alzheimer’s disease. Early studies on transgenic mice showed promising results in the reduction of amyloid plaques.However, curcumin is very poorly soluble in aqueous solutions and not easily accessible to coupling as it contains only phenolic groups as potential coupling sites. For these reasons only few imaging studies using curcumin bound as an ester were performed and curcumin is mainly used as nutritional supplement. Methods: In the present study we produced an aminoethyl ether derivative of curcumin using a nucleophilic substitution reaction. This is a small modification and should not impact the properties of curcumin while introducing an easily accessible reactive amino group. This novel compound could be used to couple curcumin to other molecules using the standard methods of peptide synthesis. We studied the aminoethyl-curcumin compound and a tripeptide carrying this aminoethyl-curcumin and the fluorescent dye fluorescein (FITC-curcumin) in vitro on cell culture using confocal laser scanning microscopy and flow cytometry. Then these two substances were tested ex vivo on brain sections prepared from transgenic mice depicting Alzheimer-like β-amyloid plaques. Results: In the in vitro CLSM microscopy and flow cytometry experiments we found dot-like unspecific uptake and only slight cytotoxicity correlating with this uptake. As these measurements were optimized for the use of fluorescein as dye we found that the curcumin at 488nm fluorescence excitation was not strong enough to use it as a fluorescence marker in these applications. In the ex vivo sections CLSM experiments both the aminoethyl-curcumin and the FITC-curcumin peptide bound specifically to β- amyloid plaques. Conclusion: In conclusion we successfully produced a novel curcumin derivative which could easily be coupled to other imaging or therapeutic molecules as a sensor for amyloid plaques.

Dehydroepiandrosterone (DHEA) and its Sulphate (DHEAS) in Alzheimer’s Disease

2020 ◽  
Vol 17 (2) ◽  
pp. 141-157 ◽  
Author(s):  
Dubravka S. Strac ◽  
Marcela Konjevod ◽  
Matea N. Perkovic ◽  
Lucija Tudor ◽  
Gordana N. Erjavec ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Large Scale ◽  
Therapeutic Potential ◽  
Relevant Literature ◽  
Comprehensive Overview ◽  
Brain Functions ◽  
Specific Effects ◽  
And Behavior

Background: Neurosteroids Dehydroepiandrosterone (DHEA) and Dehydroepiandrosterone Sulphate (DHEAS) are involved in many important brain functions, including neuronal plasticity and survival, cognition and behavior, demonstrating preventive and therapeutic potential in different neuropsychiatric and neurodegenerative disorders, including Alzheimer’s disease. Objective: The aim of the article was to provide a comprehensive overview of the literature on the involvement of DHEA and DHEAS in Alzheimer’s disease. Method: PubMed and MEDLINE databases were searched for relevant literature. The articles were selected considering their titles and abstracts. In the selected full texts, lists of references were searched manually for additional articles. Results: We performed a systematic review of the studies investigating the role of DHEA and DHEAS in various in vitro and animal models, as well as in patients with Alzheimer’s disease, and provided a comprehensive discussion on their potential preventive and therapeutic applications. Conclusion: Despite mixed results, the findings of various preclinical studies are generally supportive of the involvement of DHEA and DHEAS in the pathophysiology of Alzheimer’s disease, showing some promise for potential benefits of these neurosteroids in the prevention and treatment. However, so far small clinical trials brought little evidence to support their therapy in AD. Therefore, large-scale human studies are needed to elucidate the specific effects of DHEA and DHEAS and their mechanisms of action, prior to their applications in clinical practice.

Therapeutic Potential of Adipose-Derived Mesenchymal Stem Cells (Admscs) and/or Taurine in Aluminum Chloride-Induced Alzheimer's Disease Rat Model

2021 ◽  
Author(s):  
Mohamed Hosney ◽  
Alaa Sakraan ◽  
Aman Asaad ◽  
Mervat El-Deftar ◽  
Emad Elzayat
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Rat Model ◽  
Cell Activation ◽  
Therapeutic Potential ◽  
Brain Homogenate ◽  
Oxidative Stress Marker

Abstract Alzheimer's disease (AD) is the most prevalent type of dementia characterized by its progression, neurobehavioral and neuro-pathological characteristics, leading to a diverse neuronal loss. Adipose-derived mesenchymal stem cells (ADMSCs) have previously proved potential role in preventing the pathogenesis of several neurodegenerative disorders, so regarded as a promising new approach for AD regenerative therapy. Taurine was found to enhance stem cell activation and propagation yielding a higher concentration of neural progenitors and stem cells, and aid to lessen the number of activated microglia leading to down-regulated inflammation in vitro. The present study aimed to investigate the possible therapeutic potential of ADMSCs and/or taurine in treating AD rat model. It was planned to include three successive phases; induction, withdrawal, and therapeutic phases. Fifty male Wistar rats were divided into 2 main groups: control (C) group and AD model group. Behavioral changes, as manifested by the T-Maze experiment, had been recorded. β-amyloid levels had been measured in brain homogenate and serum by ELISA. Oxidative stress marker (MDA), and anti-oxidant enzymes activity (SOD, GSH, and CAT) in brain, as well as serum acetylcholine esterase activity were spectrophotometrically determined. Pro-apoptotic (p53 and Bax) and anti-apoptotic (Bcl2) gene expression in brain were evaluated using RT-qPCR. The histopathological alterations in brain tissues were also observed. The present study proved the potential therapeutic ability of ADMSCs and/or taurine in alleviating the adverse pathological changes induced by AlCl3 in AD rat model at both physiological and molecular levels.

Nanostructured Lipid Carriers for Intranasal Administration of Olanzapine in the management of Schizophrenia

2021 ◽  
Vol 14 ◽  
Author(s):  
Sarbjot Kaur ◽  
Ujjwal Nautiyal ◽  
Pooja A. Chawla ◽  
Viney Chawla
Keyword(s):  
Drug Delivery ◽  
Ex Vivo ◽  
In Vitro Release ◽  
Nanostructured Lipid Carriers ◽  
Polydispersity Index ◽  
Poloxamer 407 ◽  
Ex Vivo Permeation ◽  
Permeation Studies ◽  
Vitro Release

Background: Background: Olanzapine belongs to a new class of dual spectrum antipsychotic agents. It is known to show promise in managing both the positive and negative symptoms of schizophrenia. Drug delivery systems based on nanostructured lipid carriers (NLC) are expected to provide rapid nose-to-brain transport of this drug and improved distribution into and within the brain. Objective: The present study deals with the preparation and evaluation of olanzapine loaded NLC via the intranasal route for schizophrenia. Methods: Olanzapine-NLC were formulated through the solvent injection method using isopropyl alcohol as the solvent, stearic acid as solid lipid, and oleic acid as liquid lipid, chitosan as a coating agent, and Poloxamer 407 as a surfactant. NLC were characterized for particle size, polydispersity index, entrapment efficiency, pH, viscosity, X-ray diffraction studies, in-vitro mucoadhesion study, in- vitro release and ex-vivo permeation studies. The shape and surface morphology of the prepared NLC was determined through transmission electron microscopy. To detect the interaction of the drug with carriers, compatibility studies were also carried out. Results: Average size and polydispersity index of developed formulation S6 was 227.0±6.3 nm and 0.460 respectively. The encapsulation efficiency of formulation S6 was found to be 87.25 %. The pH, viscosity, in-vitro mucoadhesion study, and in- vitro release of optimized olanzapine loaded NLC were recorded as 5.7 ± 0.05, 78 centipoise, 15±2 min, and 91.96 % respectively. In ex-vivo permeation studies, the percent drug permeated after 210 min was found to be 84.03%. Conclusion: These results reveal potential application of novel olanzapine-NLC in intranasal drug delivery system for treatment of schizophrenia.

scholarly journals The Therapeutic Potential of Berberis darwinii Stem-Bark: Quantification of Berberine and In Vitro Evidence for Alzheimer's Disease Therapy

2011 ◽  
Vol 6 (8) ◽  
pp. 1934578X1100600 ◽  
Author(s):  
Solomon Habtemariam
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Charles Darwin ◽  
Potent Inhibitor ◽  
Methanolic Extract ◽  
Therapeutic Potential ◽  
Stem Bark ◽  
Acetylcholinesterase Inhibition ◽  
Disease Therapy

Berberis darwinii is native to South America but has been widely distributed in Europe and other continents following its discovery by Charles Darwin. Herewith, the therapeutic potential of stem-bark of the plant for treating Alzheimer's disease was studied using an in vitro acetylcholinesterase inhibition assay. It was found that the methanolic extract of the stem-bark was a potent inhibitor of the enzyme with an IC50 value of 1.23 ± 0.05 μg/mL. An HPLC-based berberine quantification study revealed an astonishing 38% yield of the dried methanolic extract.

scholarly journals The Therapeutic Potential of Rosemary (Rosmarinus officinalis) Diterpenes for Alzheimer’s Disease

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Solomon Habtemariam
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Therapeutic Potential ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Rosmarinus Officinalis ◽  
Brain Inflammation ◽  
Important Species

Rosemary (Rosmarinus officinalisL.) is one of the most economically important species of the family Lamiaceae. Native to the Mediterranean region, the plant is now widely distributed all over the world mainly due to its culinary, medicinal, and commercial uses including in the fragrance and food industries. Among the most important group of compounds isolated from the plant are the abietane-type phenolic diterpenes that account for most of the antioxidant and many pharmacological activities of the plant. Rosemary diterpenes have also been shown in recent years to inhibit neuronal cell death induced by a variety of agents bothin vitroandin vivo. The therapeutic potential of these compounds for Alzheimer’s disease (AD) is reviewed in this communication by giving special attention to the chemistry of the compounds along with the various pharmacological targets of the disease. The multifunctional nature of the compounds from the general antioxidant-mediated neuronal protection to other specific mechanisms including brain inflammation and amyloid beta (Aβ) formation, polymerisation, and pathologies is discussed.

scholarly journals Development and Correlation between in vitro Drug Release and in vitro Permeation of Thermally Triggered Mucoadhesive in situ Nasal Gel of Repaglinide PVP K30 Complex

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Kamla Pathak ◽  
Anil Kumar ◽  
Ekta Yadav
Keyword(s):  
Ex Vivo ◽  
Solid Dispersions ◽  
In Vitro Release ◽  
Type Ii Diabetes Mellitus ◽  
Poloxamer 407 ◽  
Ex Vivo Permeation ◽  
In Situ Nasal Gel ◽  
Pvp K30

The aim of the investigation was to develop and evaluate thermoreversible in situ nasal gel formulations of repaglinide (REP) and to establish correlation between its in vitro release and ex vivo permeation profiles. The solubility of REP was enhanced by preparing solid dispersions (SDs) with hydrophilic carriers (PVP K30/ PEG 6000/ poloxamer 188) in different weight ratios. REP: PVP K30 (1:5) was selected as the optimized SD as it showed highest enhancement in solubility (405%). The optimized SD was characterized by SEM and DSC and incorporated into a blend of thermoreversible and mucoadhesive polymers (poloxamer 407 and carbopol 934 P) by cold technique to form in situ gels (F1-F6). The prepared in-situ gels were evaluated for various pharmacotechnical features and the formulation F3 exhibited least gelling time of 6.1± 0.20, good mucoadhesive property to ensure sufficient residence time at the site of application and a %CDR of 82.25%. The ex vivo permeation characteristics across goat mucosa can be summarized as CDP of 78.7%, flux = 6.80 mg/cm2/h; permeability coefficient of 2.02 mg/h and zero order kinetics. On correlating the CDR profile of F3 with that of its CDP profile, a R2 value of 0.991 (slope= 0.921) was observed. The value of slope approximating one, suggested that almost entire amount of drug released from F3 was capable of permeating across the nasal mucosa, ex-vivo indicating that in-situ nasal gels of REP for systemic action can be successfully developed for the management non-insulin dependent type-II diabetes mellitus.

scholarly journals Therapeutic Potential Of Multifunctional Derivatives Of Cholinesterase Inhibitors

2020 ◽  
Vol 19 ◽  
Author(s):  
Maja Przybyłowska ◽  
Krystyna Dzierzbicka ◽  
Szymon Kowalski ◽  
Klaudia Chmielewska ◽  
Iwona Inkielewicz-Stepniak
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Therapeutic Potential ◽  
Amyloid Plaque ◽  
Β Amyloid ◽  
Derivatives Of ◽  
And Oxidative Stress ◽  
Pro Inflammatory Cytokines

: The aim of this work is review of tacrine analogues from the last three years, which were not included in the latest review work, donepezil and galantamine hybrids from 2015 and rivastigmine derivatives from 2014. In this account we summarize the efforts toward the development and characterization of non-toxic inhibitors of cholinesterases based on mentioned drugs with various interesting additional properties such as antioxidant, decreasing β-amyloid plaque aggregation, nitric oxide production, pro-inflammatory cytokines release, monoamine oxidase-B activity, cytotoxicity and oxidative stress in vitro and in animal model that classify these hybrids as potential multifunctional therapeutic agents for Alzheimer’s disease. Moreover, herein, we have described the cholinergic hypothesis, mechanisms of neurodegeneration and current pharmacotherapy of Alzheimer’s disease which is based on the restoration of cholinergic function through blocking enzymes that break down acetylcholine.

scholarly journals Honokiol and Pioglitazone Ameliorate Alzheimer's Disease Pathologies in vitro and ex vivo

2018 ◽  
Vol 32 (S1) ◽  
Author(s):  
Tyler Lynd ◽  
Manoj Govindarajulu ◽  
Murali Dhanasekaran ◽  
Vishnu Suppiramaniam
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Ex Vivo
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