title: Intranasal delivery of rotigotine to the brain with lactoferrin-modified PEG-PLGA nanoparticles for Parkinson's disease treatment.
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.
authors.affiliation: School 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.
authors.forename: Chenchen
authors.initials: C
authors.lastname: Bi
authors.affiliation: School 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.
authors.forename: Aiping
authors.initials: A
authors.lastname: Wang
authors.affiliation: School 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.
authors.forename: Yongchao
authors.initials: Y
authors.lastname: Chu
authors.affiliation: School 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.
authors.forename: Sha
authors.initials: S
authors.lastname: Liu
authors.affiliation: School 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.
authors.forename: Hongjie
authors.initials: H
authors.lastname: Mu
authors.affiliation: School 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.
authors.forename: Wanhui
authors.initials: W
authors.lastname: Liu
authors.affiliation: School 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.
authors.forename: Zimei
authors.initials: Z
authors.lastname: Wu
authors.affiliation: School 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.
authors.forename: Kaoxiang
authors.initials: K
authors.lastname: Sun
authors.affiliation: School 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; State Key Laboratory of Long-Acting and Targeting Drug Delivery System, Shandong Luye Pharmaceutical Co, Ltd., Yantai, People's Republic of China.
authors.forename: Youxin
authors.initials: Y
authors.lastname: Li
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000187:drug effects*; D001980:Bronchi / Q000166:cytology / Q000187:drug effects; D002478:Cells, Cultured; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D006801:Humans; D007781:Lactoferrin / Q000008:administration & dosage* / Q000737:chemistry; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009447:Neuroblastoma / Q000188:drug therapy / Q000473:pathology; D010300:Parkinson Disease / Q000188:drug therapy*; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage*; D013876:Thiophenes / Q000008:administration & dosage*; D014018:Tissue Distribution
chemical_list: D004337:Drug Carriers; D011091:Polyesters; D013764:Tetrahydronaphthalenes; D013876:Thiophenes; C000589473:polyethylene glycol-poly(lactide-co-glycolide); D011092:Polyethylene Glycols; C047508:rotigotine; D007781:Lactoferrin
keywords: Parkinson’s disease; brain targeting; intranasal delivery; lactoferrin-modified PEG-PLGA nanoparticles; rotigotine