Intranasal delivery of rotigotine to the brain with lactoferrin-modified PEG-PLGA nanoparticles for Parkinson’s disease treatment
Chenchen Bi,1,* Aiping Wang,1,* Yongchao Chu,1 Sha Liu,1 Hongjie Mu,1 Wanhui Liu,1 Zimei Wu,1 Kaoxiang Sun,1 Youxin Li1,2 1School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and...
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Dove Medical Press
2016
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oai:doaj.org-article:b498516621fa456c8458b385bea6111d2021-12-02T01:04:57ZIntranasal delivery of rotigotine to the brain with lactoferrin-modified PEG-PLGA nanoparticles for Parkinson’s disease treatment1178-2013https://doaj.org/article/b498516621fa456c8458b385bea6111d2016-12-01T00:00:00Zhttps://www.dovepress.com/intranasal-delivery-of-rotigotine-to-the-brain-with-lactoferrin-modifi-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Chenchen Bi,1,* Aiping Wang,1,* Yongchao Chu,1 Sha Liu,1 Hongjie Mu,1 Wanhui Liu,1 Zimei Wu,1 Kaoxiang Sun,1 Youxin Li1,2 1School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, 2State Key Laboratory of Long-Acting and Targeting Drug Delivery System, Shandong Luye Pharmaceutical Co, Ltd., Yantai, People’s Republic of China *These authors contributed equally to this work Abstract: Sustainable and safe delivery of brain-targeted drugs is highly important for successful therapy in Parkinson’s disease (PD). This study was designed to formulate biodegradable poly(ethylene glycol)–poly(lactic-co-glycolic acid) (PEG-PLGA) nanoparticles (NPs), which were surface-modified with lactoferrin (Lf), for efficient intranasal delivery of rotigotine to the brain for the treatment of PD. Rotigotine NPs were prepared by nanoprecipitation, and the effect of various independent process variables on the resulting properties of NPs was investigated by a Box–Behnken experimental design. The physicochemical and pharmaceutical properties of the NPs and Lf-NPs were characterized, and the release kinetics suggested that both NPs and Lf-NPs provided continuous, slow release of rotigotine for 48 h. Neither rotigotine NPs nor Lf-NPs reduced the viability of 16HBE and SH-SY5Y cells; in contrast, free rotigotine was cytotoxic. Qualitative and quantitative cellular uptake studies demonstrated that accumulation of Lf-NPs was greater than that of NPs in 16HBE and SH-SY5Y cells. Following intranasal administration, brain delivery of rotigotine was much more effective with Lf-NPs than with NPs. The brain distribution of rotigotine was heterogeneous, with a higher concentration in the striatum, the primary region affected in PD. This strongly suggested that Lf-NPs enable the targeted delivery of rotigotine for the treatment of PD. Taken together, these results demonstrated that Lf-NPs have potential as a carrier for nose-to-brain delivery of rotigotine for the treatment of PD. Keywords: rotigotine, lactoferrin-modified PEG-PLGA nanoparticles, brain targeting, intranasal delivery, Parkinson’s diseaseBi CCWang APChu YCLiu SMu HJLiu WHWu ZMSun KXLi YXDove Medical PressarticleRotigotineLactoferrin-modified PEG-PLGA nanoparticlesBrain targetingIntranasal deliveryParkinson's diseaseMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 11, Pp 6547-6559 (2016) |
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Rotigotine Lactoferrin-modified PEG-PLGA nanoparticles Brain targeting Intranasal delivery Parkinson's disease Medicine (General) R5-920 |
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Rotigotine Lactoferrin-modified PEG-PLGA nanoparticles Brain targeting Intranasal delivery Parkinson's disease Medicine (General) R5-920 Bi CC Wang AP Chu YC Liu S Mu HJ Liu WH Wu ZM Sun KX Li YX Intranasal delivery of rotigotine to the brain with lactoferrin-modified PEG-PLGA nanoparticles for Parkinson’s disease treatment |
| description |
Chenchen Bi,1,* Aiping Wang,1,* Yongchao Chu,1 Sha Liu,1 Hongjie Mu,1 Wanhui Liu,1 Zimei Wu,1 Kaoxiang Sun,1 Youxin Li1,2 1School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, 2State Key Laboratory of Long-Acting and Targeting Drug Delivery System, Shandong Luye Pharmaceutical Co, Ltd., Yantai, People’s Republic of China *These authors contributed equally to this work Abstract: Sustainable and safe delivery of brain-targeted drugs is highly important for successful therapy in Parkinson’s disease (PD). This study was designed to formulate biodegradable poly(ethylene glycol)–poly(lactic-co-glycolic acid) (PEG-PLGA) nanoparticles (NPs), which were surface-modified with lactoferrin (Lf), for efficient intranasal delivery of rotigotine to the brain for the treatment of PD. Rotigotine NPs were prepared by nanoprecipitation, and the effect of various independent process variables on the resulting properties of NPs was investigated by a Box–Behnken experimental design. The physicochemical and pharmaceutical properties of the NPs and Lf-NPs were characterized, and the release kinetics suggested that both NPs and Lf-NPs provided continuous, slow release of rotigotine for 48 h. Neither rotigotine NPs nor Lf-NPs reduced the viability of 16HBE and SH-SY5Y cells; in contrast, free rotigotine was cytotoxic. Qualitative and quantitative cellular uptake studies demonstrated that accumulation of Lf-NPs was greater than that of NPs in 16HBE and SH-SY5Y cells. Following intranasal administration, brain delivery of rotigotine was much more effective with Lf-NPs than with NPs. The brain distribution of rotigotine was heterogeneous, with a higher concentration in the striatum, the primary region affected in PD. This strongly suggested that Lf-NPs enable the targeted delivery of rotigotine for the treatment of PD. Taken together, these results demonstrated that Lf-NPs have potential as a carrier for nose-to-brain delivery of rotigotine for the treatment of PD. Keywords: rotigotine, lactoferrin-modified PEG-PLGA nanoparticles, brain targeting, intranasal delivery, Parkinson’s disease |
| format |
article |
| author |
Bi CC Wang AP Chu YC Liu S Mu HJ Liu WH Wu ZM Sun KX Li YX |
| author_facet |
Bi CC Wang AP Chu YC Liu S Mu HJ Liu WH Wu ZM Sun KX Li YX |
| author_sort |
Bi CC |
| title |
Intranasal delivery of rotigotine to the brain with lactoferrin-modified PEG-PLGA nanoparticles for Parkinson’s disease treatment |
| title_short |
Intranasal delivery of rotigotine to the brain with lactoferrin-modified PEG-PLGA nanoparticles for Parkinson’s disease treatment |
| title_full |
Intranasal delivery of rotigotine to the brain with lactoferrin-modified PEG-PLGA nanoparticles for Parkinson’s disease treatment |
| title_fullStr |
Intranasal delivery of rotigotine to the brain with lactoferrin-modified PEG-PLGA nanoparticles for Parkinson’s disease treatment |
| title_full_unstemmed |
Intranasal delivery of rotigotine to the brain with lactoferrin-modified PEG-PLGA nanoparticles for Parkinson’s disease treatment |
| title_sort |
intranasal delivery of rotigotine to the brain with lactoferrin-modified peg-plga nanoparticles for parkinson’s disease treatment |
| publisher |
Dove Medical Press |
| publishDate |
2016 |
| url |
https://doaj.org/article/b498516621fa456c8458b385bea6111d |
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