Host-guest chemistry of giant molecular shape amphiphiles based on POSS-PDI conjugates.

Giant shape amphiphiles (GSA) are giant molecules made with nano-building blocks that have distinct shapes. The incompatible packing behaviors of the nano-building blocks of GSA could create cavities within certain conformers of the GSA, but the host-guest chemistry of GSA has not been explored yet. In this study, POSS-PDI-POSS (PPP), which is made by connecting two nano-cubes, isobutyl-polyhedral oligomeric silsesquioxanes (POSS), to a conjugated π-conjugated core, perylene diimide (PDI), is demonstrated as a novel acyclic synthetic host. In its bent conformer, PPP shows a cavity next to its PDI core. Via forming host-guest complexes with π-conjugated guests such as pyrene and perylene, PPP is found to transform from the bent-conformer into the extended-conformer, creating the steric features to accommodate guest molecules. Subsequent thermal annealing of the host-guest complexes removes the π-conjugated guests and restores the bent conformation and photophysical properties of PPP, which verifies that PPP, as a novel acyclic host, is capable of dynamic host-guest assembly. Moreover, the results prove that cavities at the molecular level can be created by connecting nano-building blocks with distinct shapes. This finding may inspire developments in the host-guest chemistry of GSA and nanomaterial innovation.

High Performance Gas Separation Mixed Matrix Membrane Fabricated by Incorporation of Functionalized Submicrometer-Sized Metal-Organic Framework.

Mixed matrix membranes (MMMs) attract great attention due to their outstanding gas separation performance. The compatibility between the fillers and the polymer matrix is one of the key points for the preparation of high-performance MMMs. In this work, MMMs consisting of metal-organic frameworks (MOFs) of amine-modified Cu-BTC (NH2-Cu-BTC; BTC = 1,3,5-benzenetricarboxylic acid) and submicrometer-sized amine-modified Cu-BTC (sub-NH2-Cu-BTC) incorporated into a Pebax-1657 polymer were fabricated for the gas separation. The SEM image and Fourier transform infrared spectroscopy (FTIR) spectra showed an increase in the surface roughness of MOFs and the presence of amino groups on the surface of Cu-BTC after the amination modification, and a decrease in the size of MOFs crystals after the submicrometer-sized aminated modification. Gas adsorption analysis indicated that NH2-Cu-BTC and sub-NH2-Cu-BTC had a higher gas adsorption capacity for CO2 compared to the unmodified Cu-BTC. The scanning electron microscopy (SEM) image showed that NH2-Cu-BTC and sub-NH2-Cu-BTC, especially sub-NH2-Cu-BTC, had a better compatibility with a polyether-block-amide (Pebax) matrix in the MMMs. The gas separation performance indicated that the Pebax/sub-NH2-Cu-BTC MMMs evidently improved the CO2/N2 and CO2/CH4 selectivity at the expense of a slight CO2 permeability. The results reveal that modified MOF-filled MMMs possess great potential for applications in the CO2 separation field.

Simulation of the pharmacokinetics of bisoprolol in healthy adults and patients with impaired renal function using whole-body physiologically based pharmacokinetic modeling.

AIM: To develop and evaluate a whole-body physiologically based pharmacokinetic (WB-PBPK) model of bisoprolol and to simulate its exposure and disposition in healthy adults and patients with renal function impairment. METHODS: Bisoprolol dispositions in 14 tissue compartments were described by perfusion-limited compartments. Based the tissue composition equations and drug-specific properties such as log P, permeability, and plasma protein binding published in literatures, the absorption and whole-body distribution of bisoprolol was predicted using the 'Advanced Compartmental Absorption Transit' (ACAT) model and the whole-body disposition model, respectively. Renal and hepatic clearances were simulated using empirical scaling methods followed by incorporation into the WB-PBPK model. Model refinements were conducted after a comparison of the simulated concentration-time profiles and pharmacokinetic parameters with the observed data in healthy adults following intravenous and oral administration. Finally, the WB-PBPK model coupled with a Monte Carlo simulation was employed to predict the mean and variability of bisoprolol pharmacokinetics in virtual healthy subjects and patients. RESULTS: The simulated and observed data after both intravenous and oral dosing showed good agreement for all of the dose levels in the reported normal adult population groups. The predicted pharmacokinetic parameters (AUC, C(max), and T(max)) were reasonably consistent (<1.3-fold error) with the observed values after single oral administration of doses ranging from of 5 to 20 mg using the refined WB-PBPK model. The simulated plasma profiles after multiple oral administration of bisoprolol in healthy adults and patient with renal impairment matched well with the observed profiles. CONCLUSION: The WB-PBPK model successfully predicts the intravenous and oral pharmacokinetics of bisoprolol across multiple dose levels in diverse normal adult human populations and patients with renal insufficiency.

[Research progress on current pharmacokinetic evaluation of Chinese herbal medicines].

In order to prove safety and efficacy, herbal medicines must undergo the rigorous scientific researches such as pharmacokinetic and bioavailability, before they are put on the market in the foreign countries. Botanical Drug Products promulgated by the US FDA could guide industry sponsors to develop herbal drugs, which was also an important reference for investigating Chinese herbal medicines. This paper reviews and discusses novel approaches for how to assess systemic exposure and pharmacokinetic of Chinese herbal medicines, which were in line with FDA guidance. This mainly focus on identifying pharmacokinetic markers of botanical products, integral pharmacokinetic study of multiple components, Biopharmaceutics drug disposition classification system, and population pharmacokinetic-pharmacodynamic study in herb-drug interaction.

[Transmembrane transport and metabolism of diammonium glycyrrhizinate across rat small intestine in Ussing Chamber].

OBJECTIVE: To explore the transmembrane transport and metabolism of diammonium glycyrrhizinate in intestines of rats. METHOD: An Ussing Chamber model were used to investigate the transmembrane transport of diammonium glycyrrhizinate (GZ), the concentrations of diammonium glycyrrhizinate and its two metabolites were determined by HPLC. RESULT: The permeability coefficients of GZ in difference intestinal mucous membranes were ranged from 0.3 x 10(-6) cm x s(-1) to 1.1 x 10(-6) cm x s(-1). The metabolism of GZ in enterocytes during its transport process was negligible. The concentration of diammonium glycyrrhizinate and pH had limit effects on the transport amount and the permeability coefficients of GZ. CONCLUSION: GZ is a low permeability drug, but it can be absorbed at all segments of the small intestine in rats. Ileum is the major absorption region of GZ.

[HPLC fingerprint of Phlomis younghusbandii].

OBJECTIVE: To establish the characteristic fingerpint from Phlomis younghustbandii. METHODS: The different collecting time and county samples of Phlomis younghusbandii were determined by HPLC. RESULTS: The HPLC-FPC of Phlomis younghusbandii was set up by establishing 14 common peaks. Accuracy, stability and repeatability of the method were good. CONCLUSION: The peaks in the spectrum were all separated perfectly, which met the regulation of HPLC-FPC.

Novel sustained-release implant of herb extract using chitosan.

Chitosan (CS), a naturally occurring high-molecule polymer, which is stable in vivo, has proved to be a useful biomaterial. The extract of danshen (Radix Salviae miltiorrhizae), a medicinal herbal, was developed with CS-gelatin as an implant for the promotion of anastomosing and healing on muscles and tissues at the organic incision site in abdominal cavities. Measurements were made of the sustained release of tanshinone IIa, a marker component, from the material in vitro. The dissolution medium was assayed with an high-performance liquid chromatography method. Biodegradation studies of the material were also conducted both in vitro and in vivo. The film made of this material exhibited a sustained release effect. The release profile confirms to the Higuchi equation. At most about 20% of the incorporated drug were released over 15 days in a CS-gelatin (1:2) matrix. Drug release was found to be effectively controlled by the drug-amount loaded in the matrix. The improved film (CS/gelatin ratio: 1:16) can be hydrolyzed by lysozymes in vitro in 4 days. This film of 0.5 cm2 was implanted and degraded completely in rats over 28 days and the animals' wounds of abdominal incision healed well.