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Due to the impermeability of the blood-brain barrier and the nonselective distribution of drugs in the brain, the therapeutic access to intractable neurological disorders is challenging. In this study, dual brain-targeting polymersomes (POs) functionalized by transferrin and Tet-1 peptide (Tf/Tet-1-POs) promoted the transportation of curcumin into the brain and provided neuroprotection. The modification of the ligands that bind to the surface of POs was revealed by X-ray photoelectron spectroscopy analysis. The cell uptake of a coculture model of mouse brain capillary endothelial cells with neurons showed that the Tf/Tet-1-POs had significant transportation properties and possessed affinity for neurons. The pharmacokinetic analysis showed that the blood-brain barrier permeability-surface efficiency of the Tf/Tet-1-POs was 0.28 mL/h/g and that the brain tissue uptake rate (% ID/g) was 0.08, which were significant compared with the controls (P

Guichen Zhou,1,2,* Ying Lu,1,* He Zhang,1,* Yan Chen,1 Yuan Yu,1 Jing Gao,1 Duxin Sun,3 Guoqing Zhang,2 Hao Zou,1 Yanqiang Zhong1 1Department of Pharmaceutical Science, Second Military Medical University, Shanghai, People's Republic of China; 2Department of Pharmacy, East Hospital of Hepatobiliary Surgery, Shanghai, People's Republic of China; 3Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI, USA*These authors contributed equally to this workPurpose: The aim of this report was to introduce a novel “core-membrane” microgel drug-delivery device for spontaneously pulsed release without any external trigger.Methods: The microgel core was prepared with alginate and chitosan. The semipermeable membrane outside the microgel was made of polyelectrolytes including polycation poly(allylamine hydrochloride) and sodium polystyrene sulfonate. The drug release of this novel system was governed by the swelling pressure of the core and the rupture of the outer membrane.Results: The size of the core-membrane microgel drug-delivery device was 452.90 ± 2.71 µm. The surface charge depended on the layer-by-layer coating of polyelectrolytes, with zeta potential of 38.6 ± 1.4 mV. The confocal microscope exhibited the layer-by-layer outer membrane and inner core. The in vitro release profile showed that the content release remained low during the first 2.67 hours. After this lag time, the cumulative release increased to 80% in the next 0.95 hours, which suggested a pulsed drug release. The in vivo drug release in mice showed that the outer membrane was ruptured at approximately 3 to 4 hours, as drug was explosively released.Conclusion: These data suggest that the encapsulated substance in the core-membrane microgel delivery device can achieve a massive drug release after outer membrane rupture. This device was an effective system for pulsed drug delivery.Keywords: polyelectrolyte, chitosan–alginate, microgels, layer-by-layer, pulsed drug delivery

Due to the impermeability of the blood–brain barrier and the nonselective distribution of drugs in the brain, the therapeutic access to intractable neurological disorders is challenging. In this study, dual brain-targeting polymersomes (POs) functionalized by transferrin and Tet-1 peptide (Tf/Tet-1-POs) promoted the transportation of curcumin into the brain and provided neuroprotection. The modification of the ligands that bind to the surface of POs was revealed by X-ray photoelectron spectroscopy analysis. The cell uptake of a coculture model of mouse brain capillary endothelial cells with neurons showed that the Tf/Tet-1-POs had significant transportation properties and possessed affinity for neurons. The pharmacokinetic analysis showed that the blood–brain barrier permeability–surface efficiency of the Tf/Tet-1-POs was 0.28 mL/h/g and that the brain tissue uptake rate (% ID/g) was 0.08, which were significant compared with the controls (P