DoE based Olanzapine loaded poly-caprolactone nanoparticles decreases extrapyramidal effects in rodent model

Joseph, Emil; Reddi, Satish; Rinwa, Vibhu; Balwani, Garima; Saha, Ranendra Narayan

doi:10.1016/j.ijpharm.2018.02.010

Cited by 21 publications

(11 citation statements)

References 33 publications

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“…The disappearance of the drug endothermic peak in polymeric nanoparticles has been reported earlier (Supporting Information data, Figure S3). 37 2.2. Amyloid Fibrillation Study.…”

Section: Resultsmentioning

confidence: 99%

Biophysical, Biochemical, and Behavioral Implications of ApoE3 Conjugated Donepezil Nanomedicine in a Aβ_1–42 Induced Alzheimer’s Disease Rat Model

Krishna

Saha

Dubey

2020

ACS Chem. Neurosci.

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Alzheimer's disease (AD) is a progressive neurological disorder and is the most common type of dementia. Amyloid β (Aβ) plaques play an important role in the pathophysiology of AD. However, the existing therapeutic strategies are not effective for the management of both Aβ-induced neurotoxicity and Aβ fibrils clearance in biological conditions. Herein, we have developed lipoprotein conjugated polymeric nanoparticles that can boost the clearance rate of Aβ fibrils and mitigate Aβ-induced neurotoxicity in AD rat. These nanoparticles were designed by loading donepezil in an amphiphilic polymer with a lipoprotein (ApoE3) integrated over the surface. Polymeric nanoparticles were prepared by a nanoprecipitation method, and ApoE3 was conjugated to the polymer layer by polysorbate 80. In the present study, we intended to examine the protective effect of ApoE3 nanoparticles against Aβinduced neurotoxicity both in vitro and in vivo to evaluate if these can reduce the Aβ fibril formation and cognitive and behavioral deficits observed in AD induced rats. In the in vitro study, neurotoxicity induced by Aβ 1−42 in human neuroblastoma (SH-SY5Y) cells was found to be significantly reduced upon treatment with ApoE3 donepezil nanoparticles. The presence of the ApoE3 significantly modified the morphology of Aβ fibrils and also inhibited the formation Aβ oligomers. Moreover, in the in vivo study, following treatment, AD induced rats were tested on Morris water maze (MWM) and passive avoidance task for their cognitive ability and sacrificed for biochemical estimations. From our observations, ApoE3 donepezil nanoparticles exhibited neuroprotection in the Aβ 1−42 induced model by mitigating the pathological features and cognitive impairments. Thus, we anticipate that the nanosized lipoprotein carriers will possibly offer a rational therapeutic strategy in the formulation development of AD.

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“…The disappearance of the drug endothermic peak in polymeric nanoparticles has been reported earlier (Supporting Information data, Figure S3). 37 2.2. Amyloid Fibrillation Study.…”

Section: Resultsmentioning

confidence: 99%

Biophysical, Biochemical, and Behavioral Implications of ApoE3 Conjugated Donepezil Nanomedicine in a Aβ_1–42 Induced Alzheimer’s Disease Rat Model

Krishna

Saha

Dubey

2020

ACS Chem. Neurosci.

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“…Surface coating of optimized nanoparticles by polysorbate-80 was performed to enhance the brain uptake (D2-NPs). , In brief, freeze-dried nanoparticles were dispersed in water containing 1% of polysorbate-80 (20 mg/mL of nanoparticles). This dispersion was further bath sonicated for 10 min for complete dispersion of nanoparticles and then incubated at room temperature for 30 min.…”

Section: Methodsmentioning

confidence: 99%

Design and Biological Evaluation of Lipoprotein-Based Donepezil Nanocarrier for Enhanced Brain Uptake through Oral Delivery

Krishna

Wadhwa

Alexander

et al. 2019

ACS Chem. Neurosci.

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Alzheimer’s disease (AD) is a progressive neurodegenerative disorder associated with memory and cognitive impairment. Donepezil is an acetylcholinesterase inhibitor used for the symptomatic treatment of AD. However, high dose of donepezil is prescribed to achieve effective concentration in the brain, which leads to significant side effects, gastrointestinal alterations, and hepatotoxicity. In the present study, ApoE3 conjugated polymeric nanoparticles derived from diblock copolymer methoxy poly(ethylene glycol)–polycaprolactone (mPEG–PCL) have been used to boost the delivery of donepezil to the brain. mPEG–PCL is an amphiphilic diblock polymer with a tendency to avoid nanoparticle uptake by phagocytic cells in the liver and can significantly reduce the gastric mucosal irritations. Moreover, ApoE3-based nanocarriers showed a promising ability to enhance brain uptake, binding to amyloid beta with high affinity and accelerating its clearance. Donepezil-loaded polymeric nanoparticles were performed by using a nanoprecipitation method and further surface modified with polysorbate 80 and ApoE3 to increase the brain bioavailability and reduce the dose. Optimization of various process parameters were performed using quality by design approach. ApoE3 polymeric nanoparticles were found to be stable in simulated gastric fluids and exhibited a sustained drug release pattern. Cellular uptake studies confirmed better neuronal uptake of the developed formulation, which is further corroborated with pharmacokinetic and biodistribution studies. Orally administered ApoE3 polymeric nanoparticles resulted in significantly higher brain donepezil levels after 24 h (84.97 ± 11.54 ng/mg tissue) as compared to the pure drug (not detected), suggesting a significant role of surface coating. Together, these findings are promising and offer preclinical evidence for better brain availability of donepezil by oral administration.

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“…The innovative therapeutic approach represents a new form of pharmaceuticals-transdermal drug delivery systems-"patches" containing lipid nanocontainers with this neuroleptic [139]. In addition to improving bioavailability, a study [140] with biodegradable polymeric lipid-core nanocapsules and a decrease in extrapyramidal side effects were shown for polymeric nanoparticles polycaprolactone [141]. Animal model studies have demonstrated improved therapeutic efficacy compared to pure olanzapine [141].…”

Section: Drug Delivery For Schizophrenia and Bipolar Disordersmentioning

confidence: 99%

“…In addition to improving bioavailability, a study [140] with biodegradable polymeric lipid-core nanocapsules and a decrease in extrapyramidal side effects were shown for polymeric nanoparticles polycaprolactone [141]. Animal model studies have demonstrated improved therapeutic efficacy compared to pure olanzapine [141].…”

Section: Drug Delivery For Schizophrenia and Bipolar Disordersmentioning

confidence: 99%

Nano Carrier Drug Delivery Systems for the Treatment of Neuropsychiatric Disorders: Advantages and Limitations

et al. 2020

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Neuropsychiatric diseases are one of the main causes of disability, affecting millions of people. Various drugs are used for its treatment, although no effective therapy has been found yet. The blood brain barrier (BBB) significantly complicates drugs delivery to the target cells in the brain tissues. One of the problem-solving methods is the usage of nanocontainer systems. In this review we summarized the data about nanoparticles drug delivery systems and their application for the treatment of neuropsychiatric disorders. Firstly, we described and characterized types of nanocarriers: inorganic nanoparticles, polymeric and lipid nanocarriers, their advantages and disadvantages. We discussed ways to interact with nerve tissue and methods of BBB penetration. We provided a summary of nanotechnology-based pharmacotherapy of schizophrenia, bipolar disorder, depression, anxiety disorder and Alzheimer’s disease, where development of nanocontainer drugs derives the most active. We described various experimental drugs for the treatment of Alzheimer’s disease that include vector nanocontainers targeted on β-amyloid or tau-protein. Integrally, nanoparticles can substantially improve the drug delivery as its implication can increase BBB permeability, the pharmacodynamics and bioavailability of applied drugs. Thus, nanotechnology is anticipated to overcome the limitations of existing pharmacotherapy of psychiatric disorders and to effectively combine various treatment modalities in that direction.

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DoE based Olanzapine loaded poly-caprolactone nanoparticles decreases extrapyramidal effects in rodent model

Cited by 21 publications

References 33 publications

Biophysical, Biochemical, and Behavioral Implications of ApoE3 Conjugated Donepezil Nanomedicine in a Aβ_1–42 Induced Alzheimer’s Disease Rat Model

Biophysical, Biochemical, and Behavioral Implications of ApoE3 Conjugated Donepezil Nanomedicine in a Aβ_1–42 Induced Alzheimer’s Disease Rat Model

Design and Biological Evaluation of Lipoprotein-Based Donepezil Nanocarrier for Enhanced Brain Uptake through Oral Delivery

Nano Carrier Drug Delivery Systems for the Treatment of Neuropsychiatric Disorders: Advantages and Limitations

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DoE based Olanzapine loaded poly-caprolactone nanoparticles decreases extrapyramidal effects in rodent model

Cited by 21 publications

References 33 publications

Biophysical, Biochemical, and Behavioral Implications of ApoE3 Conjugated Donepezil Nanomedicine in a Aβ1–42 Induced Alzheimer’s Disease Rat Model

Biophysical, Biochemical, and Behavioral Implications of ApoE3 Conjugated Donepezil Nanomedicine in a Aβ1–42 Induced Alzheimer’s Disease Rat Model

Design and Biological Evaluation of Lipoprotein-Based Donepezil Nanocarrier for Enhanced Brain Uptake through Oral Delivery

Nano Carrier Drug Delivery Systems for the Treatment of Neuropsychiatric Disorders: Advantages and Limitations

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Product

Resources

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Biophysical, Biochemical, and Behavioral Implications of ApoE3 Conjugated Donepezil Nanomedicine in a Aβ_1–42 Induced Alzheimer’s Disease Rat Model

Biophysical, Biochemical, and Behavioral Implications of ApoE3 Conjugated Donepezil Nanomedicine in a Aβ_1–42 Induced Alzheimer’s Disease Rat Model