A series of ginkgolide B derivatives (GBD) were designed for delivery of ginkgolide B (GB) across the blood–brain barrier to the brain. Three GBD had shown considerable brain-targeting ability in our previous study. Among them, the ginkgolide B pyrazine (PGB) derivative was selected as a promising novel GB derivative because of its highest brain distribution. Further investigations with regard to PGB and GB's effects on inhibiting the expression of P-gp and attenuating the efflux function of P-gp were reported in this study. They were considered a big step towards better understanding the relationship between GBD's brain-targeting behavior and P-gp regulation. Western blot analysis indicated that PGB was more effective in inhibiting the expression of P-gp than GB in rat brain microvessel endothelial cells (rBMECs) and rat cerebral cortexes and hippocampus. Moreover, the efflux function of P-gp via the transportation of rhodamine 123 was significantly inhibited in PGB-treated rat brains. Preventive medication with PGB induced a better protection of the integrity of the BBB in incomplete ischemia mice. Our findings revealed that an attenuated expression level and efflux function of P-gp and improved protective effect could be realized by the ginkgolide B derivative. These investigations will pave the way for designing more efficient brain-targeting derivatives of ginkgolide and some other central nervous system drugs.
The emergence of “superbugs” is not only problematic and potentially lethal for infected subjects but also poses serious challenges for the healthcare system. Although existing antibacterial agents have been effective in some cases, the side effects and biocompatibility generally present difficulties. The development of new antibacterial agents is therefore urgently required. In this work, we have adapted a strategy for the improvement of poly(hexamethylene guanidine) hydrochloride (PHMG), a common antibacterial agent. This involves copolymerization of separate monomer units in varying ratios to find the optimum ratio of the hydrocarbon to guanidine units for antibacterial activity. A series of these copolymers, designated as PGB, was synthesized. By varying the guanidine/hydrophobic ratio and the copolymer molecular weight, a structure-optimized PGB was identified that showed broad-spectrum antibacterial activity and excellent biocompatibility in solution. In an antibacterial assay, the copolymer with the optimum composition (hydrophobic unit content 25%) inhibited >99% Staphylococcus aureus and was compatible with mammalian cells. A polyurethane emulsion containing this PGB component formed transparent, flexible films (PGB-PU films) on a wide range of substrate surfaces, including soft polymers and metals. The PGB-PU films showed excellent bacteriostatic efficiency against nosocomial drug-resistant bacteria, such as Pseudomonas aeruginosa and methicillin-resistant S. aureus (MRSA). It is concluded that our PGB polymers can be used as bacteriostatic agents generally and in particular for the design of antibacterial surfaces in medical devices.
Yu Wu,Arul Murugesan,Yaru Han,Juan Han,Yiping Chen,Huanhuan Li
An injectable BZUCNPs-PACMSNs/PGB sensor was proposed to detect AFB 1 . • BPEI was coated on ZUCNPs to improve the water-soluble ability of ZUCNPs • A dual-gated strategy was presented to improve the stability of UCNPs sensor. • BPEI@Cu 2+ can effectively quench the fluorescence of ZUCNPs due to IFE. • Injectable PGB hydrogel was utilized for stable and on-site AFB 1 detection. An expanding presence of aflatoxin B 1 (AFB 1 ) contamination across the global food supply represents a serious threat to public health. This work developed a portable sensor using Zn 2+ -doped upconversion nanoparticles (ZUCNPs) that Cu 2+ -induced fluorescence quenching with an injectable polyvinyl alcohol/gelatin/borax (PGB) hydrogel. First, ZUCNPs exhibiting enhanced fluorescence were modified with branched polyethylenimine (BPEI) to form signal probes known as BZUCNPs. Additionally, mesoporous silica nanoparticles (MSNs) were fabricated via sol-gel methods, loaded with Cu 2+ and coated with aptamer (Apt) and polydopamine (PDA) to create dual-gated capture probes (PACMSNs). Afterwards, BZUCNPs and PACMSNs were mixed to form sensing probes and then integrated into the PGB hydrogel, forming the final sensor (BZUCNPs-PACMSNs/PGB). In the presence of AFB 1 at pH 5.5, the AFB 1 diffused into the PGB hydrogel, disrupting the PDA and Apt layer due to acid environment and changing the structure of Apt as AFB 1 specifically bound to it. Then, Cu 2+ released and facilitated the formation of BPEI@Cu 2+ complex on the surface of ZUCNPs, which produced inner filter effect (IFE) that quenched fluorescence. When experimental conditions were optimized, a pronounced linear calibration curve ( R 2 = 0.994) was observed, linking fluorescence to the logarithm of AFB 1 levels across a 0.1–100 μg/kg AFB 1 range. And its sensitivity was characterized with a detection limit of 0.03 μg/kg. Furthermore, the sensor's applicability was confirmed through analysis of food matrices, including wheat, corn, peanuts, and water, yielding high analytical accuracy with relative standard deviations below 6.08% and recovery rates ranging from 93.77% to 107.67%.
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