静电纺纤维滴鼻液实现脑室内给药

Adequate drug delivery across the blood–brain barrier(BBB) is a critical factor in treating central nervous system(CNS) disorders. Inspired by swimming fish and the microstructure of the nasal cavity, this study is the first to develop swimming short fibrous nasal drops that can directly target the nasal mucosa and swim in the nasal cavity, which can effectively deliver drugs to the brain. Briefly, swimming short fibrous nasal drops with charged controlled drug release were fabricated by electrospinning, homogenization,the π-π conjugation between indole group of fibers, the benzene ring of leucine-rich repeat kinase 2(LRRK2) inhibitor along with charge-dipole interaction between positively charged poly-lysine(PLL)and negatively charged surface of fibers;this enabled these fibers to stick to nasal mucosa, prolonged the residence time on mucosa, and prevented rapid mucociliary clearance. In vitro, swimming short fibrous nasal drops were biocompatible and inhibited microglial activation by releasing an LRRK2 inhibitor. In vivo, luciferase-labelled swimming short fibrous nasal drops delivered an LRRK2 inhibitor to the brain through the nasal mucosa, alleviating cognitive dysfunction caused by sepsis-associated encephalopathy by inhibiting microglial inflammation and improving synaptic plasticity. Thus, swimming short fibrous nasal drops is a promising strategy for the treatment of CNS diseases.

Polymerization of methyl methacrylate catalyzed by mono-/bis-salicylaldiminato nickel(Ⅱ) complexes and methylaluminoxane

Two types of salicylaldiminato-based nickel complexes,mono-ligated Ni(II)complexes([O-C_(6)H_(4)-o-C(H)=N-Ar]Ni(PPh_(3))(Ph)(5),[O-(3,5-Br_(2))C_(6)H_(2)-o-C(H)=N-Ar]Ni(PPh_(3))(Ph)(6),[O-(3-t-Bu)C_(6)H_(3)-o-C(H)=N-Ar]Ni(PPh_(3))(Ph)(7))and bis-ligated Ni(II)complexes([O-(3,5-Br_(2))C_(6)H_(2)-o-C(H)=N-Ar]_(2)Ni(8),[O-(3,5-Br_(2))C_(6)H_(2)-o-C(H)=N-2-C_(6)H_(4)(PhO)]_(2)Ni(9),Ar=2,6-C_(6)H_(3)(i-Pr)_(2))were synthesized and characterized by Fourier transform infrared spectroscopy(FT-IR),nuclear magnetic resonance(NMR),mass spectrography(MS)and elemental analysis(EA).In the presence of methylaluminoxane(MAO)as cocatalyst,all the nickel complexes exhibited high activities for the polymerization of methyl methacrylate(MMA)and syndiotactic-rich poly(methyl methacrylate)(PMMA)was obtained.The complexes with less bulky substituents on salicylaldiminato framework possessed higher activities,while with the same salicylaldiminato,the mono-ligated nickel complexes showed higher catalytic activity than bis-ligated ones.

Chronic treatment with anesthetic propofol attenuates β-amyloid protein levels in brain tissues of aged mice

Alzheimer’s disease(AD)is the most common form of dementia.At the present time,however,AD still lacks effective treatments.Our recent studies showed that chronic treatment with anesthetic propofol attenuated brain caspase-3 activation and improved cognitive function in aged mice.Accumulation ofβ-amyloid protein(Aβ)is a major component of the neuropathogenesis of AD dementia and cognitive impairment.We therefore set out to determine the effects of chronic treatment with propofol on Aβlevels in brain tissues of aged mice.Propofol(50 mg/kg)was administrated to aged(18 month-old)wild-type mice once a week for 8 weeks.The brain tissues of mice were harvested one day after the final propofol treatment.The harvested brain tissues were then subjected to enzyme-linked immunosorbent assay(ELISA)and Western blot analysis.Here we report that the propofol treatment reduced Aβ(Aβ40 and Aβ42)levels in the brain tissues of the aged mice.Moreover,the propofol treatment decreased the levels ofβ-site amyloid precursor protein cleaving enzyme(the enzyme for Aβgeneration),and increased the levels of neprilysin(the enzyme for Aβdegradation)in the brain tissues of the aged mice.These results suggested that the chronic treatment with propofol might reduce brain Aβlevels potentially via decreasing brain levels ofβ-site amyloid precursor protein cleaving enzyme,thus decreasing Aβgeneration;and via increasing brain neprilysin levels,thus increasing Aβdegradation.These preliminary findings from our pilot studies have established a system and postulated a new hypothesis for future research.