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ABSTRACTIntroductionBiphasic release, as a special drug-modified release profile that combines immediate and sustained release, allows fast therapeutic action and retains blood drug concentration for long periods. Electrospun nanofibers, particularly those with complex nanostructures produced by multi-fluid electrospinning processes, are potential novel biphasic drug delivery systems (DDSs).Areas coveredThis review summarizes the most recent developments in electrospinning and related structures. In this review, the role of electrospun nanostructures in biphasic drug release was comprehensively explored. These electrospun nanostructures include monolithic nanofibers obtained through single-fluid blending electrospinning, core-shell and Janus nanostructures prepared via bifluid electrospinning, three-compartment nanostructures obtained via trifluid electrospinning, nanofibrous assemblies obtained through the layer-by-layer deposition of nanofibers, and the combined structure of electrospun nanofiber mats with casting films. The strategies and mechanisms through which complex structures facilitate biphasic release were analyzed.Expert opinionElectrospun structures can provide many strategies for the development of biphasic drug release DDSs. However, many issues such as the scale-up productions of complex nanostructures, the in vivo verification of the biphasic release effects, keeping pace with the developments of multi-fluid electrospinning, drawing support from the state-of-the-art pharmaceutical excipients, and the combination with traditional pharmaceutical methods need to be addressed for real applications.

•Study on retinal detachment matched with finite element analysis and experiments•Prediction of traumatic retinal detachment based on stress and strain

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Organophosphorus compounds (OPs) pose great military and civilian hazards. However, therapeutic and prophylactic antidotes against OP poisoning remain challenging. In this study, we first developed a novel nanoscavenger (rOPH/ZIF-8@E-Lipo) against methyl paraoxon (MP) poisoning using enzyme immobilization and erythrocyte–liposome hybrid membrane camouflage techniques. Then, we evaluated the physicochemical characterization, stability, and biocompatibility of the nanoscavengers. Afterward, we examined acetylcholinesterase (AChE) activity, cell viability, and intracellular reactive oxygen species (ROS) to indicate the protective effects of the nanoscavengers in vitro. Following the pharmacokinetic and biodistribution studies, we further evaluated the therapeutic and prophylactic detoxification efficacy of the nanoscavengers against MP in various poisoning settings. Finally, we explored the penetration capacity of the nanoscavengers across the blood–brain barrier (BBB). The present study validated the successful construction of a novel nanoscavenger with excellent stability and biocompatibility. In vitro, the resulting nanoscavenger exhibited a significant protection against MP-induced AChE inactivation, oxidative stress, and cytotoxicity. In vivo, apart from the positive therapeutic effects, the nanoscavengers also exerted significant prophylactic detoxification efficacy against single lethal MP exposure, repeated lethal MP challenges, and sublethal MP poisoning. These excellent detoxification effects of the nanoscavengers against OPs may originate from a dual-mode mechanism of inner recombinant organophosphorus hydrolase (rOPH) and outer erythrocyte membrane-anchored AChE. Finally, in vitroand in vivostudies jointly demonstrated that monosialoganglioside (GM1)-modified rOPH/ZIF-8@E-Lipo could penetrate the BBB with high efficiency. In conclusion, a stable and safe dual-modal nanoscavenger was developed with BBB penetration capability, providing a promising strategy for the treatment and prevention of OP poisoning.

Aims:HIF1-α is an important transcription factor in the regulation of the immune response. The protective function of HIF1-α in the host epithelial immune response to Aspergillus fumigatusrequires further clarification. Methods:In this study we demonstrated the effect of upregulation of HIF1-α expression in A549 cells and mouse airway cells exposed to A. fumigatus in vivo. Results:The killing capacity was enhanced by boosting proinflammatory factors both in vitroand in vivo. Moreover, airway inflammation was reduced in the HIF1-α-upregulated mice. Conclusion:We identified a protective role for HIF1-α in anti-A. fumigatusimmunity. Modulation of HIF1-α might be a target for the development of aspergillosis therapy.