Metabolic profile of Fructus Gardeniae in human plasma and urine using ultra high-performance liquid chromatography coupled with high-resolution LTQ-orbitrap mass spectrometry

<p>1.In China, Fructus Gardeniae was used as a traditional Chinese medicine (TCM) with a wide array of biological activities. The bioactive components identified in Fructus Gardeniae mainly included iridoids, flavonids, pigments, and so on. Among them, iridoids were regarded as important compounds in Fructus Gardeniae. Though analyses of the constituents in biological samples after oral administration of Fructus Gardeniae effective fraction or its active compounds have been reported, few efforts have been made to investigate the metabolic profile of Fructus Gardeniae in humans. In this study, the constituents and metabolites of Fructus Gardeniae in human blood and urine after oral administration of Fructus Gardeniae were investigated using ultra high-performance liquid chromatography (UHPLC) coupled with high-resolution LTQ-Orbitrap mass spectrometery.</p> <p>2.Totally, 14 constituents (two parent compounds and 12 metabolites) of Fructus Gardeniae were identified in human plasma and urine either by comparing the retention time and mass spectrometry data with that of reference compounds or by the accurate high-resolution MS/MS data of the chemicals. The compounds identified were mainly iridoid glycosides such as geniposide and the derivatives of genipin-O-glucuronide. Among them, 11 metabolites were detected in human plasma and urine while the other three metabolites including geniposidic acid (M1), demethylation derivative of genipin-O-glucuronide (M2), and dehydration product of mono-hydroxylated genipin-O-glucuronide (M9) were only discovered in human urine. Further, the possible metabolic pathways of Fructus Gardeniae <i>in vivo</i> were proposed and the peak area–time curve of the most abundant metabolite genipin-O-glucuronide (M13) in human plasma after oral administration of Fructus Gardeniae was depicted. The results suggested that a metabolic difference existed between rats and humans.</p> <p>3.The results obtained in the present research would provide basic information to understand the metabolic profile of Fructus Gardeniae in humans and explore the chemicals responsible for the hepatotoxicity of Fructus Gardeniae <i>in vivo</i>. Moreover, it would be beneficial for us to further study the pharmacokinetic behavior of Fructus Gardeniae in humans systematically.</p

Core–Shell Chitosan Microcapsules for Programmed Sequential Drug Release

A novel type of core–shell chitosan microcapsule with programmed sequential drug release is developed by the microfluidic technique for acute gastrosis therapy. The microcapsule is composed of a cross-linked chitosan hydrogel shell and an oily core containing both free drug molecules and drug-loaded poly­(lactic-<i>co</i>-glycolic acid) (PLGA) nanoparticles. Before exposure to acid stimulus, the resultant microcapsules can keep their structural integrity without leakage of the encapsulated substances. Upon acid-triggering, the microcapsules first achieve burst release due to the acid-induced decomposition of the chitosan shell. The encapsulated free drug molecules and drug-loaded PLGA nanoparticles are rapidly released within 60 s. Next, the drugs loaded in the PLGA nanoparticles are slowly released for several days to achieve sustained release based on the synergistic effect of drug diffusion and PLGA degradation. Such core–shell chitosan microcapsules with programmed sequential drug release are promising for rational drug delivery and controlled-release for the treatment of acute gastritis. In addition, the microcapsule systems with programmed sequential release provide more versatility for controlled release in biomedical applications

Controllable Multicompartmental Capsules with Distinct Cores and Shells for Synergistic Release

A facile and flexible approach is developed for controllable fabrication of novel multiple-compartmental calcium alginate capsules from all-aqueous droplet templates with combined coextrusion minifluidic devices for isolated coencapsulation and synergistic release of diverse incompatible components. The multicompartmental capsules exhibit distinct compartments, each of which is covered by a distinct part of a heterogeneous shell. The volume and number of multiple compartments can be well-controlled by adjusting flow rates and device numbers for isolated and optimized encapsulation of different components, while the composition of different part of the heterogeneous shell can be individually tailored by changing the composition of droplet template for flexibly tuning the release behavior of each component. Two combined devices are first used to fabricate dual-compartmental capsules and then scaled up to fabricate more complex triple-compartmental capsules for coencapsulation. The synergistic release properties are demonstrated by using dual-compartmental capsules, which contain one-half shell with a constant release rate and the other half shell with a temperature-dependent release rate. Such a heterogeneous shell provides more flexibilities for synergistic release with controllable release sequence and release rates to achieve advanced and optimized synergistic efficacy. The multicompartmental capsules show high potential for applications such as drug codelivery, confined reactions, enzyme immobilizations, and cell cultures

Uniform Microparticles with Controllable Highly Interconnected Hierarchical Porous Structures

A simple and versatile strategy is developed for one-step fabrication of uniform polymeric microparticles with controllable highly interconnected hierarchical porous structures. Monodisperse water-in-oil-in-water (W/O/W) emulsions, with methyl methacrylate, ethylene glycol dimethacrylate, and glycidyl methacrylate as the monomer-containing oil phase, are generated from microfluidics and used for constructing the microparticles. Due to the partially miscible property of oil/aqueous phases, the monodisperse W/O/W emulsions can deform into desired shapes depending on the packing structure of inner aqueous microdrops, and form aqueous nanodrops in the oil phase. The deformed W/O/W emulsions allow template syntheses of highly interconnected hierarchical porous microparticles with precisely and individually controlled pore size, porosity, functionality, and particle shape. The microparticles elaborately combine the advantages of enhanced mass transfer, large functional surface area, and flexibly tunable functionalities, providing an efficient strategy to physically and chemically achieve enhanced synergetic performances for extensive applications. This is demonstrated by using the microparticles for oil removal for water purification and protein adsorption for bioseparation. The method proposed in this study provides full versatility for fabrication of functional polymeric microparticles with controllable hierarchical porous structures for enhancing and even broadening their applications