Improved dissolution and oral absorption by co-grinding active drug probucol and ternary stabilizers mixtures with planetary beads-milling method

The objective of this work is to construct a nanosuspension drug delivery system of probucol,a BCS II drug,in order to improve its dissolution and oral bioavailability.The wet milling procedure using planetary beads-milling equipment was utilized to grind the raw probucol to ultrafine nanoparticle/nanocrystal aqueous suspension that was further solidified by freeze-drying process.Cellulose derivatives of different substitution groups and molecular weights,including HPMC,HPC,and MC,were evaluated as the primary stabilizer of probucol nanosuspension.Ternary stabilizers system composed of a primary stabilizer(cellulose derivative,i.e.HPC),a nonionic surfactant(Pluronic R F68),and an anionic surfactant(SDS)was employed to obtain probucol nanosuspension of finer particle size and enhanced dissolution in aqueous media.The probucol nanosuspension with good physical stability showed no obvious change of particle size even after storing over 7 d at 4°C or 25°C.The solidified probucol nanosuspension with trehalose as the cryoprotectant showed the highest dissolution rate(>60%at 2 h)compared to other cryoprotectant.The in vivo pharmacokinetic evaluation indicated about 15-folds higher AUC value of the probucol nanosuspension compared to that of coarse probucol suspension after oral administration to rats.The probucol nanosuspension prepared by wet-milling and ternary stabilizers system may find wide applications for improving the dissolution and oral absorption of water-insoluble drugs.

A recombinase polymerase amplification with lateral flow assay for rapid on-the-spot detection of Aeromonas salmonicida

Aeromonas salmonicida is a common pathogen of salmonid fishes that poses a significant threat to the fresh water and marine culture industry,potentially resulting in huge economic losses.To prevent and control fish diseases caused by A.salmonicida,rapid and effective diagnostic approaches must be developed,and which are important for routine monitoring and clinical care.By combining recombinase polymerase amplification(RPA)technology with a visible lateral flow strip(RPA-LF),we have enhanced both the precision of RPA detection and the convenience of real-time monitoring.In this study,we introduce a robust method for detecting A.salmonicida using RPA-LF.This assay specifically targets the ASA_1441 gene of A.salmonicida,ensuring high specificity,without cross-reactivity with other prevalent fresh water or marine pathogens.The optimal amplification temperature of the RPA assay was 39℃.Its sensitivity extends to as low as 100 fg of purified DNA,representing more than 1000-fold higher sensitivity than conventional PCR methods.Furthermore,to enhance the usability of the RPA-LF assay,we developed a rapid sample preparation method using cellulose dipsticks for nucleic acid extraction.This method achieves a limit of detection(LOD)as low as 1.67 CFU/μL and completes the entire process within 20 min.In conclusion,our findings present a rapid and precise tool for monitoring A.salmonicida infection in aquaculture and marine culture.This advancement offers valuable insights for effective disease prevention and control strategies.