Astaxanthin-loaded brain-permeable liposomes for Parkinson’s disease treatment via antioxidant and anti-inflammatory responses
Abstract Parkinson’s disease is a neurodegenerative disorder characterized by cardinal motor symptoms resulting from the loss of dopaminergic neurons in the substantia nigra pars compacta. Although current medications may alleviate its symptoms, Parkinson’s disease remains incurable. Astaxanthin is...
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BMC
2025-02-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-025-03104-8 |
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| author | Thai-Duong Nguyen Shristi Khanal Eunhee Lee Jinsol Choi Ganesh Bohara Nikesh Rimal Dong-Young Choi Soyeun Park |
| author_facet | Thai-Duong Nguyen Shristi Khanal Eunhee Lee Jinsol Choi Ganesh Bohara Nikesh Rimal Dong-Young Choi Soyeun Park |
| author_sort | Thai-Duong Nguyen |
| collection | DOAJ |
| description | Abstract Parkinson’s disease is a neurodegenerative disorder characterized by cardinal motor symptoms resulting from the loss of dopaminergic neurons in the substantia nigra pars compacta. Although current medications may alleviate its symptoms, Parkinson’s disease remains incurable. Astaxanthin is an antioxidant and anti-inflammatory agent; however, its high susceptibility to oxidative degradation and low aqueous solubility limit its therapeutic efficacy. This study aimed to improve the pharmaceutical properties and neuroprotective effects of astaxanthin for Parkinson’s disease treatment by using lactoferrin-conjugated astaxanthin-loaded liposomes (Lf-ASX-LPs). We successfully formulated Lf-ASX-LPs with high encapsulation efficiency (97.6%) and favorable physical characteristics (diameter: 109.8 ± 1.1 nm; polydispersity index: 0.18 ± 0.01; zeta potential: − 9.5 ± 1.1 mV). Lf-functionalized liposomes demonstrated enhanced cellular uptake and permeation in a Transwell® study, showing a 16.7-fold higher internalization in SH-SY5Y cells over 24 h than those without Lf conjugation. Additionally, Lf functionalization enhanced brain penetration ability, as demonstrated by a biodistribution study using nude mice, compared to LPs without Lf conjugation. In vitro, Lf-ASX-LPs reduced cell loss by 20.1% and oxygen species by 30.0%, ameliorated the reduction in mitochondrial membrane potential under 1-methyl-4-phenylpyridinium-induced toxicity by 40.1%, and reduced extracellular nitric oxide levels under lipopolysaccharide-induced toxicity by 32.0%, indicating cytoprotective and antioxidant effects. In a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson’s disease mouse model, treatment with Lf-ASX-LPs resulted in 5.0-, 3.1-, and 5.6-fold increases in dopamine levels, TH+ fiber density, and TH+ neurons, respectively, restoring dopaminergic neuron damage. The developed formulation also alleviated behavioral impairment and neuroinflammation, reducing astrocyte and microglial activation in the striatum and substantia nigra of the MPTP-treated animals. Thus, our formulation of Lf-ASX-LPs represents a promising strategy for providing neuroprotection and retarding Parkinson’s disease progression. Graphical abstract |
| format | Article |
| id | doaj-art-01df13f707434e6485944df973511c80 |
| institution | Kabale University |
| issn | 1477-3155 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-01df13f707434e6485944df973511c802025-02-09T12:53:11ZengBMCJournal of Nanobiotechnology1477-31552025-02-0123112210.1186/s12951-025-03104-8Astaxanthin-loaded brain-permeable liposomes for Parkinson’s disease treatment via antioxidant and anti-inflammatory responsesThai-Duong Nguyen0Shristi Khanal1Eunhee Lee2Jinsol Choi3Ganesh Bohara4Nikesh Rimal5Dong-Young Choi6Soyeun Park7College of Pharmacy, Keimyung UniversityCollege of Pharmacy, Yeungnam UniversityCollege of Pharmacy, Keimyung UniversityCollege of Pharmacy, Keimyung UniversityCollege of Pharmacy, Yeungnam UniversityCollege of Pharmacy, Yeungnam UniversityCollege of Pharmacy, Yeungnam UniversityCollege of Pharmacy, Keimyung UniversityAbstract Parkinson’s disease is a neurodegenerative disorder characterized by cardinal motor symptoms resulting from the loss of dopaminergic neurons in the substantia nigra pars compacta. Although current medications may alleviate its symptoms, Parkinson’s disease remains incurable. Astaxanthin is an antioxidant and anti-inflammatory agent; however, its high susceptibility to oxidative degradation and low aqueous solubility limit its therapeutic efficacy. This study aimed to improve the pharmaceutical properties and neuroprotective effects of astaxanthin for Parkinson’s disease treatment by using lactoferrin-conjugated astaxanthin-loaded liposomes (Lf-ASX-LPs). We successfully formulated Lf-ASX-LPs with high encapsulation efficiency (97.6%) and favorable physical characteristics (diameter: 109.8 ± 1.1 nm; polydispersity index: 0.18 ± 0.01; zeta potential: − 9.5 ± 1.1 mV). Lf-functionalized liposomes demonstrated enhanced cellular uptake and permeation in a Transwell® study, showing a 16.7-fold higher internalization in SH-SY5Y cells over 24 h than those without Lf conjugation. Additionally, Lf functionalization enhanced brain penetration ability, as demonstrated by a biodistribution study using nude mice, compared to LPs without Lf conjugation. In vitro, Lf-ASX-LPs reduced cell loss by 20.1% and oxygen species by 30.0%, ameliorated the reduction in mitochondrial membrane potential under 1-methyl-4-phenylpyridinium-induced toxicity by 40.1%, and reduced extracellular nitric oxide levels under lipopolysaccharide-induced toxicity by 32.0%, indicating cytoprotective and antioxidant effects. In a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson’s disease mouse model, treatment with Lf-ASX-LPs resulted in 5.0-, 3.1-, and 5.6-fold increases in dopamine levels, TH+ fiber density, and TH+ neurons, respectively, restoring dopaminergic neuron damage. The developed formulation also alleviated behavioral impairment and neuroinflammation, reducing astrocyte and microglial activation in the striatum and substantia nigra of the MPTP-treated animals. Thus, our formulation of Lf-ASX-LPs represents a promising strategy for providing neuroprotection and retarding Parkinson’s disease progression. Graphical abstracthttps://doi.org/10.1186/s12951-025-03104-8AstaxanthinLiposomeLactoferrinParkinson’s diseaseDopamine |
| spellingShingle | Thai-Duong Nguyen Shristi Khanal Eunhee Lee Jinsol Choi Ganesh Bohara Nikesh Rimal Dong-Young Choi Soyeun Park Astaxanthin-loaded brain-permeable liposomes for Parkinson’s disease treatment via antioxidant and anti-inflammatory responses Journal of Nanobiotechnology Astaxanthin Liposome Lactoferrin Parkinson’s disease Dopamine |
| title | Astaxanthin-loaded brain-permeable liposomes for Parkinson’s disease treatment via antioxidant and anti-inflammatory responses |
| title_full | Astaxanthin-loaded brain-permeable liposomes for Parkinson’s disease treatment via antioxidant and anti-inflammatory responses |
| title_fullStr | Astaxanthin-loaded brain-permeable liposomes for Parkinson’s disease treatment via antioxidant and anti-inflammatory responses |
| title_full_unstemmed | Astaxanthin-loaded brain-permeable liposomes for Parkinson’s disease treatment via antioxidant and anti-inflammatory responses |
| title_short | Astaxanthin-loaded brain-permeable liposomes for Parkinson’s disease treatment via antioxidant and anti-inflammatory responses |
| title_sort | astaxanthin loaded brain permeable liposomes for parkinson s disease treatment via antioxidant and anti inflammatory responses |
| topic | Astaxanthin Liposome Lactoferrin Parkinson’s disease Dopamine |
| url | https://doi.org/10.1186/s12951-025-03104-8 |
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