Chitosan nanocarrier for FTY720 enhanced delivery retards Parkinson’s disease via PP2A-EzH2 signaling in vitro and ex vivo

Sardoiwala, Mohammed Nadim; Karmakar, Surajit; Choudhury, Subhasree Roy

doi:10.1016/j.carbpol.2020.117435

Cited by 26 publications

(46 citation statements)

References 60 publications

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“…The initial release is normally associated with the diffusion and deposition of the surface layer of drug molecules. 30 Accordingly, these data reinforced the encapsulation index of approximately 90% of previously recorded data. Therefore, after 8 h, the drug release was close to 80% at pH 5.0 and still approximately 10% at pH 7.4.…”

Section: Resultssupporting

confidence: 82%

Modulating Fingolimod (FTY720) Anti-SARS-CoV-2 Activity Using a PLGA-Based Drug Delivery System

Miranda

Ferreira

Souza

et al. 2022

ACS Appl. Bio Mater.

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COVID-19 has resulted in more than 490 million people being infected worldwide, with over 6 million deaths by April 05th, 2022. Even though the development of safe vaccine options is an important step to reduce viral transmission and disease progression, COVID-19 cases will continue to occur, and for those cases, efficient treatment remains to be developed. Here, a drug repurposing strategy using nanotechnology is explored to develop a therapy for COVID-19 treatment. Nanoparticles (NPs) based on PLGA for fingolimod (FTY720) encapsulation show a size of ∼150 nm and high drug entrapment (∼90%). The NP (NP@FTY720) can control FTY720 release in a pH-dependent manner. Cytotoxicity assays using different cell lines show that NP@FTY720 displays less toxicity than the free drug. Flow cytometry and confocal microscopy reveal that NPs are actively internalized mostly through caveolin-mediated endocytosis and macropinocytosis pathways and co-localized with lysosomes. Finally, NP@FTY720 not only exhibits anti-SARS-CoV-2 activity at non-cytotoxic concentrations, but its biological potential for viral infection inhibition is nearly 70 times higher than that of free drug treatment. Based on these findings, the combination of drug repurposing and nanotechnology as NP@FTY720 is presented for the first time and represents a promising frontline in the fight against COVID-19.

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Section: Resultssupporting

confidence: 82%

Modulating Fingolimod (FTY720) Anti-SARS-CoV-2 Activity Using a PLGA-Based Drug Delivery System

Miranda

Ferreira

Souza

et al. 2022

ACS Appl. Bio Mater.

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“…Recently, Sardoiwala et al obtained chitosan‐based FTY720 nanoformulation, which was a highly effective targeted therapeutic agent owing to its enhanced biocompatibility and bioavailability. They further found that the formulation exhibited neuroprotective features for PD prevention by the downregulation of PD hallmark phosphoserine 129 α‐synuclein both in vivo and in vitro (Sardoiwala et al, 2021).…”

Section: Sphingolipidsmentioning

confidence: 99%

Bioactive lipids and their metabolism: New therapeutic opportunities for Parkinson's disease

Shen

Jiang

Zhao

et al. 2022

Eur J of Neuroscience

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Parkinson's disease (PD) is a neurological disorder characterized by motor dysfunction, which can also be associated with non‐motor symptoms. Its pathogenesis is thought to stem from a loss of dopaminergic neurons in the substantia nigra pars compacta and the formation of Lewy bodies containing aggregated α‐synuclein. Recent works suggested that lipids might play a pivotal role in the pathophysiology of PD. In particular, the so‐called ‘bioactive’ lipids whose changes in the concentration may lead to functional consequences and affect many pathophysiological processes, including neuroinflammation, are closely related to PD in terms of symptoms, disease progression and incidence. This study aimed to explore the molecular metabolism and physiological functions of bioactive lipids, such as fatty acids (mainly unsaturated fatty acids), eicosanoids, endocannabinoids, oxysterols, representative sphingolipids, diacylglycerols and lysophosphatidic acid, in the development of PD. The knowledge of bioactive lipids in PD gained through preclinical and clinical studies is expected to improve the understanding of disease pathogenesis and provide novel therapeutic avenues.

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“…In recent years, compared with the traditional drug delivery systems, nanoparticles (NPs) have been reported for easy drug delivery through the blood-brain barrier (BBB) into the central nervous system (CNS), and they can promote neuroprotective efficiency in neurodegenerative diseases. − Recently, metformin nanoformulation (metformin-loaded polydopamine nanoparticles) was considered as a metformin-delivery system with the aim to mediate ubiquitination and proteasomal degradation of aggregated pSer129 α-syn, replenishing dopamine loss which is associated with PD pathology . Furthermore, the latest study has shown that chitosan nanocarrier for FTY720 enhanced delivery mediated ubiquitination and degradation of agglomerated pSer129 α-syn via PP2A-EzH2 signaling in vitro and ex vivo , enhancing regulation for PD prevention . Thus, it can be seen that the application of nanomaterials in PD has potential value, and it is expected to be transformed and assessed for the novel therapeutic approach against PD.…”

Section: Ptms Of α-Synmentioning

confidence: 99%

“…105 Furthermore, the latest study has shown that chitosan nanocarrier for FTY720 enhanced delivery mediated ubiquitination and degradation of agglomerated pSer129 α-syn via PP2A-EzH2 signaling in vitro and ex vivo, enhancing regulation for PD prevention. 106 Thus, it can be seen that the application of nanomaterials in PD has potential value, and it is expected to be transformed and assessed for the novel therapeutic approach against PD.…”

Section: T H I S C O N T E N T I S O N L Y L I C E N S E D F O R C O ...mentioning

confidence: 99%

Effects of α-Synuclein-Associated Post-Translational Modifications in Parkinson’s Disease

Wang

Yung

et al. 2021

ACS Chem. Neurosci.

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α-Synuclein (α-syn), a small highly conserved presynaptic protein containing 140 amino acids, is thought to be the main pathological hallmark in related neurodegenerative disorders. Although the normal function of α-syn is closely involved in the regulation of vesicular neurotransmission in these diseases, the underlying mechanisms of post-translational modifications (PTMs) of α-syn in the pathogenesis of Parkinson's disease (PD) have not been fully characterized. The pathological accumulation of misfolded α-syn has a critical role in PD pathogenesis. Recent studies of factors contributing to α-syn-associated aggregation and misfolding have expanded our understanding of the PD disease process. In this Review, we summarize the structure and physiological function of α-syn, and we further highlight the major PTMs (namely phosphorylation, ubiquitination, nitration, acetylation, truncation, SUMOylation, and O-GlcNAcylation) of α-syn and the effects of these modifications on α-syn aggregation, which may elucidate mechanisms for PD pathogenesis and lay a theoretical foundation for clinical treatment of PD.

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Chitosan nanocarrier for FTY720 enhanced delivery retards Parkinson’s disease via PP2A-EzH2 signaling in vitro and ex vivo

Cited by 26 publications

References 60 publications

Modulating Fingolimod (FTY720) Anti-SARS-CoV-2 Activity Using a PLGA-Based Drug Delivery System

Modulating Fingolimod (FTY720) Anti-SARS-CoV-2 Activity Using a PLGA-Based Drug Delivery System

Bioactive lipids and their metabolism: New therapeutic opportunities for Parkinson's disease

Effects of α-Synuclein-Associated Post-Translational Modifications in Parkinson’s Disease

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