Background An intimidating challenge to transporting drugs into the brain parenchyma is the presence of the blood–brain barrier (BBB). Glucose is an essential nutritional substance for brain function sustenance, which cannot be synthesized by the brain. Its transport primarily depends on the glucose transporters on the brain capillary endothelial cells. In this paper, the brain-targeted properties of glucose-modified liposomes using polyethylene glycols with different chain lengths as the linkers were compared and evaluated to establish an optimized drug-delivery system. Methods Coumarin 6-loaded liposomes (GLU200-LIP, GLU400-LIP, GLU1000-LIP, and GLU2000-LIP) composed of phospholipids and glucose-derived cholesterols were prepared by thin-film dispersion-ultrasound method. The BBB model in vitro was developed to evaluate the transendothelial ability of the different liposomes crossing the BBB. The biodistribution of liposomes in the mice brains was identified by in vivo and ex vivo nearinfrared fluorescence imaging and confocal laser scanning microscopy and further analyzed quantitatively by high-performance liquid chromatography. Results Glucose-derived cholesterols were synthesized and identified, and coumarin 6-loaded liposomes were prepared successfully. The particle sizes of the four types of glucose-modified liposomes were around or smaller than 100 nm with a polydispersity index less than 0.300. GLU400-LIP, GLU1000-LIP, and GLU2000-LIP achieved higher cumulative cleared volumes on BBB model in vitro after 6 hours compared with GLU200-LIP ( P < 0.05) and were significantly higher than that of the conventional liposome ( P < 0.001). The qualitative and quantitative biodistribution results in the mice showed that the accumulation of GLU1000-LIP in the brain was the highest among all the groups ( P < 0.01 versus LIP). Conclusion The data indicated that GLU400-LIP, GLU1000-LIP, and GLU2000-LIP all possess the potential of brain targeting, among which GLU1000-LIP, as a promising drug-delivery system, exhibited the strongest brain delivery capacity.

New glycosyl derivative of cholesterol was synthesized as a material for preparing novel liposome to overcome the ineffective delivery of normal drug formulations to brain by targeting the (glucose transporters) GLUTs on the BBB. Coumarin-6 was used as fluorescent probe. The results have shown that the cytotoxicity for the brain capillary endothelial cells (BCECs) of the glucose-mediated brain targeting liposome containing coumarin-6 was less than that of conventional liposome. The BBB model in vitro was established by coculturing of BCECs and astrocytes (ACs) of rat to test the transendothelial ability crossing the BBB. The transendothelial ability was confirmed strengthen alone with the amount of the new glycosyl derivative of cholesterol used in liposome. After i.v. administration of LIP, control liposome (CLP), and GLP-4, the AUC(0-t) of coumarin-6 for GLP-4 was 2.85 times higher than that of LIP, and 3.33 times higher than that of CLP. The C(max) of CLP-4 was 1.43 times higher than that of LIP, and 3.10 times higher than that of CLP. Both pharmacokinetics and distribution in mice were also investigated to show that this novel brain targeting drug delivery system was promising.

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A new ent-kaurane diterpenoid dimer, fritillebinide C(1) together with one known diterpenoid dimer fritillebinide B (2) were isolated from the bulbs of Fritillaria ebeiensis G.D. Yu et G.Q. Ji. Compound 1 has been determined to be ent-3beta-acetoxy-kauran-16beta,17-acetal ent-16beta-kauran-17(S)-aldehyde(1) by means of spectral analysis and chemical evidence.

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