Intranasal route: The green corridor for Alzheimer's disease therapeutics

Chaudhury, Sutapa Som; Sinha, Koel; Mukhopadhyay, Chitrangada Das

doi:10.1016/j.jddst.2021.102791

Cited by 3 publications

(2 citation statements)

References 196 publications

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“…Being in the vicinity of the cerebrospinal uid (CSF) and the direct nervous interface to the brain, the highly vascularized olfactory region offers direct access to drugs from nose to brain [18]. This intra-nasal pathway provides a non-invasive mode of drug delivery as well as the stability to the peptide-based drugs of AD from degradation by plasma-trypsin, chymotrypsin, and other plasmatic enzymes [19,20]. This nose to brain delivery is also advantageous in terms of high adsorption of large molecules avoiding gastrointestinal degradation and rst-pass effect in the liver [18,20].…”

Section: Introductionmentioning

confidence: 99%

“…This intra-nasal pathway provides a non-invasive mode of drug delivery as well as the stability to the peptide-based drugs of AD from degradation by plasma-trypsin, chymotrypsin, and other plasmatic enzymes [19,20]. This nose to brain delivery is also advantageous in terms of high adsorption of large molecules avoiding gastrointestinal degradation and rst-pass effect in the liver [18,20].…”

Section: Introductionmentioning

confidence: 99%

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Rodent Model Preclinical Assessment of PEGylated Block Copolymer Targeting Cognition and Oxidative Stress Insults of Alzheimer’s Disease

et al. 2023

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Misfolded peptide amyloid beta (Aβ 42 ), neuro brillary tangles of hyper-phosphorylated tau, oxidative damage to the brain, neuroin ammation are distinguished determinants of Alzheimer's disease (AD) responsible for disease progression. This multifaceted neurodegenerative disease is challenging to cure under a single treatment regime until the key disease-determinants are traced for their sequential occurrence in disease progression. In an early report, a novel side-chain tripeptide containing PEGylated block copolymer has been tested thoroughly in vitro and in silico for the early inhibition of Aβ 42aggregation as well as degradation of preformed Aβ 42 -bril deposits. The present study demonstrates a preclinical assessment of the PEGylated block copolymer in colchicine-induced AD mimicking rodent model. The colchicine induced Wistar rats receiving an intranasal delivery of the block copolymer at a daily dosage of 100 µg/kg and 200 µg/kg body weights respectively for 14 days manifested a notable attenuation of behavioral de cit pattern, oxidative stress, and neurotransmitters' de ciency as compared to the untreated ones. The current study also reports the ameliorative property of the PEGylated compound for progressive neuroin ammation and decreased mitochondrial bioenergetics in astrocytoma cell line viz. U87. A closer look into the drug mechanism of action of a compact three-dimensional PEGylated block copolymer con rmed its disintegrative interaction with Aβ 42 bril via in silico simulation.The results obtained herein this study signify the potential of the novel PEGylated block copolymer to ameliorate the cognitive decline and progressive oxidative insults in AD, and may envision a successful clinical phase trial.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Rodent Model Preclinical Assessment of PEGylated Block Copolymer Targeting Cognition and Oxidative Stress Insults of Alzheimer’s Disease

et al. 2023

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Murine model preclinical assessment of PEGylated block copolymer targeting cognition and oxidative stress insults of Alzheimer’s disease

Chaudhury

Nandi

Kumar

et al. 2022

Preprint

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Misfolded peptide amyloid beta (Aβ42), neurofibrillary tangles of hyper-phosphorylated tau, oxidative damage to the brain, neuroinflammation are distinguished determinants of Alzheimer’s disease (AD) responsible for disease progression. This multifaceted neurodegenerative disease is challenging to cure under a single treatment regime until the key disease-determinants are traced for their sequential occurrence in disease progression. In an early report, a novel side-chain tripeptide containing PEGylated block copolymer has been tested thoroughly in vitro and in silico for the early inhibition of Aβ42-aggregation as well as degradation of preformed Aβ42-fibril deposits. The present study demonstrates a preclinical assessment of the PEGylated block copolymer in colchicine-induced AD mimicking murine model. The colchicine induced Wistar rats receiving an intranasal delivery of the block copolymer at a daily dosage of 100 µg/kg and 200 µg/kg body weights respectively for 14 days manifested a notable attenuation of behavioral deficit pattern, oxidative stress, and neurotransmitters’ deficiency as compared to the untreated ones. The current study also reports the ameliorative property of the PEGylated compound for progressive neuroinflammation and decreased mitochondrial bioenergetics in astrocytoma cell line viz. U87. A closer look into the drug mechanism of action of a compact three-dimensional PEGylated block copolymer confirmed its disintegrative interaction with Aβ42 fibril via an in silico simulation. The results obtained herein this study signify the potential of the novel PEGylated block copolymer to ameliorate the cognitive decline and progressive oxidative insults in AD, and may envision a successful clinical phase trial.

show abstract

Rodent model preclinical assessment of PEGylated block copolymer targeting cognition and oxidative stress insults of Alzheimer’s disease

Chaudhury

Nandi

Kumar

et al. 2022

Preprint

View full text Add to dashboard Cite

Misfolded peptide amyloid beta (Aβ42), neurofibrillary tangles of hyper-phosphorylated tau, oxidative damage to the brain, neuroinflammation are distinguished determinants of Alzheimer’s disease (AD) responsible for disease progression. This multifaceted neurodegenerative disease is challenging to cure under a single treatment regime until the key disease-determinants are traced for their sequential occurrence in disease progression. In an early report, a novel side-chain tripeptide containing PEGylated block copolymer has been tested thoroughly in vitro and in silico for the early inhibition of Aβ42-aggregation as well as degradation of preformed Aβ42-fibril deposits. The present study demonstrates a preclinical assessment of the PEGylated block copolymer in colchicine-induced AD mimicking rodent model. The colchicine induced Wistar rats receiving an intranasal delivery of the block copolymer at a daily dosage of 100 µg/kg and 200 µg/kg body weights respectively for 14 days manifested a notable attenuation of behavioral deficit pattern, oxidative stress, and neurotransmitters’ deficiency as compared to the untreated ones. The current study also reports the ameliorative property of the PEGylated compound for progressive neuroinflammation and decreased mitochondrial bioenergetics in astrocytoma cell line viz. U87. A closer look into the drug mechanism of action of a compact three-dimensional PEGylated block copolymer confirmed its disintegrative interaction with Aβ42 fibril via in silico simulation. The results obtained herein this study signify the potential of the novel PEGylated block copolymer to ameliorate the cognitive decline and progressive oxidative insults in AD, and may envision a successful clinical phase trial.

show abstract

Intranasal route: The green corridor for Alzheimer's disease therapeutics

Cited by 3 publications

References 196 publications

Rodent Model Preclinical Assessment of PEGylated Block Copolymer Targeting Cognition and Oxidative Stress Insults of Alzheimer’s Disease

Rodent Model Preclinical Assessment of PEGylated Block Copolymer Targeting Cognition and Oxidative Stress Insults of Alzheimer’s Disease

Murine model preclinical assessment of PEGylated block copolymer targeting cognition and oxidative stress insults of Alzheimer’s disease

Rodent model preclinical assessment of PEGylated block copolymer targeting cognition and oxidative stress insults of Alzheimer’s disease

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