Cholesterol-PEG comodified poly (N-butyl) cyanoacrylate nanoparticles for brain delivery: in vitro and in vivo evaluations.
This study investigated cholesterol-polyethylene glycol (PEG) comodified poly (ethyleneglycol)-poly (lactide) nanoparticles (CLS-PEG NPs) as a novel, biodegradable brain drug delivery system and included an evaluation of its in vitro and in vivo properties. To this end, coumarin-6 (C6), a fluorescent probe, was encapsulated into CLS-PEG NPs by an emulsion polymerization method. We reported that the use of CLS-PEG NPs led to a sustained drug release in vitro. Additionally, cell viability experiments confirmed their safety. The uptake and transport of CLS-PEG NPs, by bEnd.3 cells (an immortalized mouse brain endothelial cell line), was significantly higher than that of a control C6 solution. An investigation of the uptake mechanisms of different NP formulations demonstrated that cholesterol modifications may be the primary way to improve the efficiency of cellular uptake, wherein macropinocytosis may be the most important endocytic pathway in this process. An investigation of the transport mechanisms of CLS-PEG NPs also implicated macropinocytosis, energy and cholesterol in bEnd.3 cells lines. Following an intravenous (IV) administration to rats, pharmacokinetic experiments indicated that C6-loaded CLS-PEG NPs achieved sustained release for up to 12 h. In addition, IV delivery of CLS-PEG NPs appeared to significantly improve the ability of C6 to pass through the blood-brain barrier: the concentration of C6 found in the brain increased nearly 14.2-fold when C6 CLS-PEG NPs were used rather than a C6 solution. These in vitro and in vivo results strongly suggest that CLS-PEG NPs are a promising drug delivery system for targeting the brain, with low toxicity.
a Department of Pharmacology , Xuanwu Hospital of Capital Medical University, Beijing Institute for Brain Disorders, Key Laboratory for Neurodegenerative Diseases of Ministry of Education , Beijing , China and.
Xiao
X
Hu
b Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China.
Feifei
F
Yang
b Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China.
Yonghong
Y
Liao
a Department of Pharmacology , Xuanwu Hospital of Capital Medical University, Beijing Institute for Brain Disorders, Key Laboratory for Neurodegenerative Diseases of Ministry of Education , Beijing , China and.
Lin
L
Li
a Department of Pharmacology , Xuanwu Hospital of Capital Medical University, Beijing Institute for Brain Disorders, Key Laboratory for Neurodegenerative Diseases of Ministry of Education , Beijing , China and.
Lan
L
Zhang
D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002784:Cholesterol / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000737:chemistry*; D003374:Coumarins / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D004659:Enbucrilate / Q000737:chemistry*; D042783:Endothelial Cells / Q000378:metabolism; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D011091:Polyesters / Q000737:chemistry; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D013844:Thiazoles / Q000737:chemistry
D003374:Coumarins; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011091:Polyesters; D013844:Thiazoles; C517282:coumarin 6; C118255:polyethylene glycol-cholesterol; D011100:Polyglycolic Acid; D011092:Polyethylene Glycols; C033616:poly(lactide); D002784:Cholesterol; D004659:Enbucrilate
Cholesterol; PEG; blood–brain barrier; brain delivery; poly (N-butyl) cyanoacrylate nanoparticles