Theoretical design for covering Engeletin with functionalized nanostructure-lipid carriers as neuroprotective agents against Huntington’s disease via the nasal-brain route

Smriti,; Singla, M; Gupta, S; Porwal, O; Nasser Binjawhar, D; Sayed, AA; Mittal, P; El-Demerdash, FM; Algahtani, M; Singh, SK; Dua, K; Gupta, G; Bawa, P; Altyar, AE; Abdel-Daim, MM

Theoretical design for covering Engeletin with functionalized nanostructure-lipid carriers as neuroprotective agents against Huntington’s disease via the nasal-brain route

Smriti, Singla, M Gupta, S Porwal, O Nasser Binjawhar, D Sayed, AA Mittal, P El-Demerdash, FM Algahtani, M Singh, SK Dua, K

Gupta, G Bawa, P Altyar, AE Abdel-Daim, MM

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Publisher:: Frontiers Media SA
Publication Type:: Journal Article
Citation:: Frontiers in Pharmacology, 14

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Field	Value	Language
dc.contributor.author	Smriti,
dc.contributor.author	Singla, M
dc.contributor.author	Gupta, S
dc.contributor.author	Porwal, O
dc.contributor.author	Nasser Binjawhar, D
dc.contributor.author	Sayed, AA
dc.contributor.author	Mittal, P
dc.contributor.author	El-Demerdash, FM
dc.contributor.author	Algahtani, M
dc.contributor.author	Singh, SK
dc.contributor.author	Dua, K https://orcid.org/0000-0002-7507-1159
dc.contributor.author	Gupta, G
dc.contributor.author	Bawa, P
dc.contributor.author	Altyar, AE
dc.contributor.author	Abdel-Daim, MM
dc.date.accessioned	2023-07-12T19:05:09Z
dc.date.available	2023-07-12T19:05:09Z
dc.identifier.citation	Frontiers in Pharmacology, 14
dc.identifier.issn	1663-9812
dc.identifier.uri	http://hdl.handle.net/10453/171470
dc.description.abstract	<jats:p><jats:bold>Objective:</jats:bold> To propose a theoretical formulation of engeletin-nanostructured lipid nanocarriers for improved delivery and increased bioavailability in treating Huntington’s disease (HD).</jats:p><jats:p><jats:bold>Methods:</jats:bold> We conducted a literature review of the pathophysiology of HD and the limitations of currently available medications. We also reviewed the potential therapeutic benefits of engeletin, a flavanol glycoside, in treating HD through the Keap1/nrf2 pathway. We then proposed a theoretical formulation of engeletin-nanostructured lipid nanocarriers for improved delivery across the blood-brain barrier (BBB) and increased bioavailability.</jats:p><jats:p><jats:bold>Results:</jats:bold> HD is an autosomal dominant neurological illness caused by a repetition of the cytosine-adenine-guanine trinucleotide, producing a mutant protein called Huntingtin, which degenerates the brain’s motor and cognitive functions. Excitotoxicity, mitochondrial dysfunction, oxidative stress, elevated concentration of ROS and RNS, neuroinflammation, and protein aggregation significantly impact HD development. Current therapeutic medications can postpone HD symptoms but have long-term adverse effects when used regularly. Herbal medications such as engeletin have drawn attention due to their minimal side effects. Engeletin has been shown to reduce mitochondrial dysfunction and suppress inflammation through the Keap1/NRF2 pathway. However, its limited solubility and permeability hinder it from reaching the target site. A theoretical formulation of engeletin-nanostructured lipid nanocarriers may allow for free transit over the BBB due to offering a similar composition to the natural lipids present in the body a lipid solubility and increase bioavailability, potentially leading to a cure or prevention of HD.</jats:p><jats:p><jats:bold>Conclusion:</jats:bold> The theoretical formulation of engeletin-nanostructured lipid nanocarriers has the potential to improve delivery and increase the bioavailability of engeletin in the treatment of HD, which may lead to a cure or prevention of this fatal illness.</jats:p>
dc.language	en
dc.publisher	Frontiers Media SA
dc.relation.ispartof	Frontiers in Pharmacology
dc.relation.isbasedon	10.3389/fphar.2023.1218625
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	1115 Pharmacology and Pharmaceutical Sciences
dc.subject.classification	3214 Pharmacology and pharmaceutical sciences
dc.title	Theoretical design for covering Engeletin with functionalized nanostructure-lipid carriers as neuroprotective agents against Huntington’s disease via the nasal-brain route
dc.type	Journal Article
utslib.citation.volume	14
utslib.for	1115 Pharmacology and Pharmaceutical Sciences
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Health
pubs.organisational-group	/University of Technology Sydney/Faculty of Health/Graduate School of Health
pubs.organisational-group	/University of Technology Sydney/Faculty of Health/Graduate School of Health/GSH.Pharmacy
utslib.copyright.status	open_access	*
dc.date.updated	2023-07-12T19:05:03Z
pubs.publication-status	Published online
pubs.volume	14

Abstract:

Objective: To propose a theoretical formulation of engeletin-nanostructured lipid nanocarriers for improved delivery and increased bioavailability in treating Huntington’s disease (HD).Methods: We conducted a literature review of the pathophysiology of HD and the limitations of currently available medications. We also reviewed the potential therapeutic benefits of engeletin, a flavanol glycoside, in treating HD through the Keap1/nrf2 pathway. We then proposed a theoretical formulation of engeletin-nanostructured lipid nanocarriers for improved delivery across the blood-brain barrier (BBB) and increased bioavailability.Results: HD is an autosomal dominant neurological illness caused by a repetition of the cytosine-adenine-guanine trinucleotide, producing a mutant protein called Huntingtin, which degenerates the brain’s motor and cognitive functions. Excitotoxicity, mitochondrial dysfunction, oxidative stress, elevated concentration of ROS and RNS, neuroinflammation, and protein aggregation significantly impact HD development. Current therapeutic medications can postpone HD symptoms but have long-term adverse effects when used regularly. Herbal medications such as engeletin have drawn attention due to their minimal side effects. Engeletin has been shown to reduce mitochondrial dysfunction and suppress inflammation through the Keap1/NRF2 pathway. However, its limited solubility and permeability hinder it from reaching the target site. A theoretical formulation of engeletin-nanostructured lipid nanocarriers may allow for free transit over the BBB due to offering a similar composition to the natural lipids present in the body a lipid solubility and increase bioavailability, potentially leading to a cure or prevention of HD.Conclusion: The theoretical formulation of engeletin-nanostructured lipid nanocarriers has the potential to improve delivery and increase the bioavailability of engeletin in the treatment of HD, which may lead to a cure or prevention of this fatal illness.

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http://hdl.handle.net/10453/171470