Multimetallic CuCoNi Oxide Nanowires In Situ Grown on a Nickel Foam Substrate Catalyze Persulfate Activation via Mediating Electron Transfer.

In situ growth of nanostructures on substrates is a strategy for designing highly efficient catalytic materials. Herein, multimetallic CuCoNi oxide nanowires are synthesized in situ on a three-dimensional nickel foam (NF) substrate (CuCoNi-NF) by a hydrothermal method and applied to peroxydisulfate (PDS) activation as immobilized catalysts. The catalytic performance of CuCoNi-NF is evaluated through the degradation of organic pollutants such as bisphenol A (BPA) and practical wastewater. The results indicate that the NF not only plays an important role as the substrate support but also serves as an internal Ni source for material fabrication. CuCoNi-NF exhibits high activity and stability during PDS activation as it mediates electron transfer from BPA to PDS. CuCoNi-NF first donates electrons to PDS to arrive at an oxidized state and subsequently deprives electrons from BPA to return to the initial state. CuCoNi-NF maintains high catalytic activity in the pH range of 5.2-9.2, adapts to a high ionic strength up to 100 mM, and resists background HCO3- and humic acid. Meanwhile, 76.6% of the total organic carbon can be removed from packaging wastewater by CuCoNi-NF-catalyzed PDS activation. This immobilized catalyst shows promising potential in wastewater treatment, well addressing the separation and recovery of conventional powdered catalysts.

Discovery of Indolinone-Based Multikinase Inhibitors as Potential Therapeutics for Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a serious and deadly disease for which treatment options are limited. The recent approval of antifibrosis agent nintedanib represents one of the first therapeutic approaches for the treatment of IPF. Here, we report novel indolinone-based multikinase inhibitors that target angiogenesis and fibrosis pathways and may serve as potential therapeutics for IPF. KBP-7018 is a novel, tyrosine kinase-selective inhibitor with potent effects on three fibrotic kinases (c-KIT, PDGFR, and RET). The pharmacokinetics (PK) properties of KBP-7018 were favorable in mice, rats, and dogs. In a bleomycin (BLM)-induced mouse pulmonary fibrosis model, 10, 30, and 100 mg/kg daily doses (q.d.) of KBP-7018 improved the 28-day survival rate in a dose-dependent manner. The improved efficacy of KBP-7018 compared to nintedanib provided a certain level of chemical validation for the involvement of PDGFR, c-KIT, and RET in IPF. Thus, KBP-7018 represents a novel multikinase inhibitor with differentiated activity, highly enhanced selectivity, and acceptable PK profiles that will enter phase I clinical trials.

[The swelling behavior of choline fenofibrate hydrogel matrix tablets using dynamic image analysis].

The purpose of this study is to investigate the effects of formulation on the swelling behavior of choline fenofibrate hydrogel matrix tablets and reveal the relation between swelling property and release profile using dynamic image analysis. The volume swelling ratio (SR) and height/width (k) could evaluate the swelling behavior of matrix tablets well. The mount of hydroxypropyl methylcellulose (HPMC) and the ratio between K15M and K4M affected the volume swelling ratio, while PVP didn't. The three factors all impacted k, which was an indicator of the strength of the gel formed by HPMC. The accumulative release ratio and SR, the rate of swelling and the rate of release were compared. The proper model equations were established for the results with an excellent correlation. The results prove that there is a strong relevance between the swelling behavior and release property. This study provides a guideline in the study design for hydrogel matrix tablets.

[Preparation and properties of thermosensitive in situ gel for ophthalmic formulation containing pearl hydrolyzate].

The study was designed to generate an ophthalmic thermosensitive in situ gel with improved mechanical and mucoadhesive properties that may prolong the retention time to enhance the bioavalability of pearl hydrolyzate. The gene was comprised of poloxamer 407, poloxamer188 and Carbopol 934, which were optimized by central composite design and response surface methodology. The rheological properties, transcorneal permeability, retention time and in vitro release behaviors of the optimal gel formulation were investigated. The gel was Newtonian liquid at 25 ℃ and performed as a semisolid gel with non-Newtonian liquid property with a gelation time of 13 s at 35 ℃. Compared with a conventional eye drops, the ophthalmic in situ gel exhibited a sevenfold increase in retention with a sustained release behavior, which was observed with suitable permeability coefficient at 5.58 cm·s-1. In conclusion, the new gel of pearl hydrolyzate prolonged the release duration of drug, which may decrease the frequency of administration of pearl hydrolyzate.

Biomimetic synthesized bimodal nanoporous silica: Bimodal mesostructure formation and application for ibuprofen delivery.

The present paper innovatively reports bimodal nanoporous silica synthesized using biomimetic method (B-BNS) with synthesized polymer (C16-L-serine) as template. Formation mechanism of B-BNS was deeply studied and exploration of its application as carrier of poorly water-soluble drug ibuprofen (IBU) was conducted. The bimodal nanopores and curved mesoscopic channels of B-BNS were achieved due to the dynamic self-assembly of C16-L-serine induced by silane coupling agent (3-aminopropyltriethoxysilane, APTES) and silica source (tetraethoxysilane, TEOS). Characterization results confirmed the successful synthesis of B-BNS, and particularly, nitrogen adsorption/desorption measurement demonstrated that B-BNS was meso-meso porous silica material. In application, B-BNS loaded IBU with high drug loading content due to its enlarged nanopores. After being loaded, IBU presented amorphous phase because nanoporous space and curved mesoscopic channels of B-BNS prevented the crystallization of IBU. In vitro release result revealed that B-BNS controlled IBU release with two release phases based on bimodal nanopores and improved dissolution in simulated gastric fluid due to crystalline conversion of IBU. It is convincible that biomimetic method provides novel theory and insight for synthesizing bimodal nanoporous silica, and unique functionalities of B-BNS as drug carrier can undoubtedly promote the application of bimodal nanoporous silica and development of pharmaceutical science.

Mutual interaction between guest drug molecules and host nanoporous silica xerogel studied using central composite design.

In the present study, three water-soluble drugs (propranolol hydrochloride, PNH; diltiazem hydrochloride, DZH; levofloxacin hydrochloride, LFH) with different number of hydrogen bonding acceptors were used as guest drug molecules, and three kinds of biomimetic synthesized nanoporous silica@poly(ethyleneimine)s xerogel (NS@P xerogel, 25%NS@P xerogel and 75%NS@P xerogel) were taken as host drug carriers. Mutural interaction formed between guest drug molecules and host drug carriers were investigated using a two-level three-factorial central composite design. The results confirmed that water-soluble drug loaded three nanoporous silica carriers presented the same regular controlled release effect, which was 75%NS@P xerogel>25%NS@P xerogel>NS@P xerogel. The main contribution to burst release was the pore diameter of host carrier. Accomplishment of cumulative release in 24h can be obtained when loading guest drug molecules with small number of hydrogen bonding acceptors to host carriers with either quite small or large pore diameter. The present work can favor to explore the mutural interaction between host carrier and guest drug molecules and thus promoted the development of nanoporous silica in pharmaceutical application.

Characterization of preclinical in vitro and in vivo pharmacokinetics properties for KBP-7018, a new tyrosine kinase inhibitor candidate for treatment of idiopathic pulmonary fibrosis.

KBP-7018 is a novel selective tyrosine kinase inhibitor with potential for the treatment of idiopathic pulmonary fibrosis. The objective of this study was to characterize the preclinical pharmacokinetics of KBP-7018 in vitro and in vivo, and then to assess the likelihood of developing KBP-7018 as a clinical candidate. The systemic clearance (CL) of KBP-7018 was relatively low in rodents and monkeys with a value of less than 30% of hepatic blood flow, while it was high in dogs. The steady-state volume of distribution (V ss) ranged from 1.51 L/kg to 4.65 L/kg across the species tested. The maximum concentration (C max) of KBP-7018 occurred at 0.25-6 hours after oral dosing, and the bioavailability was moderate (21%-68%). The human CL (~20% of hepatic blood flow) and V ss (1.6-5.3 L/kg) were predicted by allometric scaling method and together with the other modeling methods indicated low metabolism and acceptable half-time (4.8-19.3 hours) in vivo. Overall, the preclinical data make it amenable to further oral solid dosage from design for the upcoming Phase I trials in human.