Chitosan/silk fibroin nanofibers-based hierarchical sponges accelerate infected diabetic wound healing via a HClO self-producing cascade catalytic reaction.

The diabetic chronic wound healing is extremely restricted by issues such as hyperglycemia, excessive exudate and reactive oxygen species (ROS), and bacterial infection, causing significant disability and fatality rate. Herein, the chitosan/silk fibroin nanofibers-based hierarchical 3D sponge (CSSF-P/AuGCs) with effective exudate transfer and wound microenvironment modulation are produced by integrating cascade reactor (AuGC) into sponge substrates with parallel-arranged microchannels. When applied to diabetic wounds, the uniformly parallel-arranged microchannels endow CSSF-P/AuGCs with exceptional exudate absorption capacity, keeping the wound clean and moist; additionally, AuGCs efficiently depletes glucose in wounds to generate H2O2, which is then converted into HClO via cascade catalytic reaction to eliminate bacterial infection and reduce inflammation. Experiments in vitro demonstrated that the antibacterial activity of CSSF-P/AuGCs against S. aureus and E. coli was 92.7 and 94.27 %, respectively. Experiments on animals indicated that CSSF-P/AuGC could cure wounds in 11 days, displaying superior wound-healing abilities when compared to the commercial medication Tegaderm™. This versatile CSSF-P/AuGCs dressing may be an attractive choice for expediting diabetic wound healing with little cytotoxicity, providing a novel therapeutic method for establishing a favorable pathological microenvironment for tissue repair.

Development of phospholipid complex loaded self-microemulsifying drug delivery system to improve the oral bioavailability of resveratrol.

Aim: The aim of this study was to develop a formulation that combines a phospholipid complex (PC) and self-microemulsifying drug delivery system (SMEDDS) to improve the bioavailability of poorly water-soluble resveratrol (RES), called RPC-SMEDDS. Methods: RES-PC (RPC) and RPC-SMEDDS were optimized by orthogonal experiment and central composite design, respectively. The characteristics and mechanism of intestinal absorption were studied by Ussing chamber model. The pharmacokinetics was evaluated in rats. Results: RES was the substrate of MRP2 and breast cancer resistance protein (BCRP) rather than P-gp. The prepared RPC-SMEDDS prevented the efflux mediated by MRP2 and BCRP and improved the bioavailability of RES. Conclusion: These results suggested that the combination system of PC and SMEDDS was a promising method to improve the oral bioavailability of RES.

Study on improvement of chiral separation of capillary electrophoresis based on cyclodextrin by deep eutectic solvents.

For the first time, the mechanism of deep eutectic solvents (DESs) improving chiral separation by capillary electrophoresis has been studied. The capillary electrophoresis chiral separation has been improved by using DESs as the auxiliary additive. Taking tropicamide, homatropine hydrochloride, ofloxacin, atenolol and propranolol hydrochloride as model chiral separation targets and cyclodextrin (CD) as the chiral selector, and the effects of DESs on the chiral separation resolution were investigated on the basis of optimized conditions. The results of fluorescence spectrophotometry and non-aqueous capillary electrophoresis showed that DESs can improve the resolution of the enantiomers, and the coordination mechanism of DESs was also explored. After DESs were added, the resolution of the above enantiomers increased from 1.26, 1.70, 5.10, 1.90, 2.02 to 3.02, 4.10, 6.86, 2.84 and 5.51 respectively, and the binding constant of CD with propranolol hydrochloride increased from 23 M-1 to 142 M-1. The results showed that DESs is an effective auxiliary additive to improve the separation efficiency of capillary electrophoresis with CD as a basic chiral additive.

[Methods and techniques of capillary electrophoresis for drug screening].

Capillary electrophoresis (CE) shows enormous potential for application in new drug research and development. Because of the aqueous medium employed as the running buffer in CE, drug screening can be carried out in an environment similar to that in physiological testing media. Drug screening methods based on CE are different from other instrumental measurements in vitro. CE can not only sustain the biological activity of the screened molecules and ligands, but also help evaluate the interactions between the receptors and the ligands. Based on these interactions, some important pharmacological parameters related to drug screening, such as the association constant Kb, bonding rate constant Kon, and dissociation rate constant Koff, can be determined by CE. Thus, CE is an effective tool for simulating and predicting the entire interaction process between receptors and drugs in vivo. In this review, the history of CE for drug screening is revisited. The theories, common methods for drug screening by CE, and some application examples and related technologies are reviewed. The methods of drug screening by means of affinity CE and kinetic CE are introduced. Some selected studies on different ligands at the molecular and cellular level are reported, along with examples several types of drugs. Techniques based on a combination of CE with mass spectrometry and chemiluminescence are reviewed, with focus on the screening of candidate drugs and active compounds from traditional Chinese medicine. The application prospect of drug screening by CE combined with a DNA-encoded compound library is introduced. This paper discusses the core of the fraction collection step in CE and emphasizes the significance of combining CE with systematic evolution of ligands by exponential enrichment. In conclusion, various optional methods for CE drug screening would pave the way for new concepts related to drug screening and evaluation in the future.

Evaluation of Intestinal Absorption Mechanism and Pharmacokinetics of Curcumin-Loaded Galactosylated Albumin Nanoparticles.

BACKGROUND: Most of the oral drugs have the properties of weak intestinal absorption and low bioavailability, which leads to little treatment to diseases. By nanotechnology, these drugs can be efficiently delivered to pass biological barriers and promote the cell uptake ability for the enhancement of the oral bioavailability. METHODS: The present work chose the prepared curcumin-loaded galactosylated albumin nanoparticles (Gal-BSA NPs) as the nano-drug samples to study the intestinal capacity and the oral bioavailability. RESULTS: The cell uptake assay showed that the Gal-BSA NPs could promote the internalization of more curcumin into the Caco-2 cells. Moreover, the cell uptake mechanism of Gal-BSA-Cur NPs depended on the clathrin-mediated endocytosis transport. The intestinal permeation assay using one Ussing chamber exhibited that the absorptive amounts of curcumin in Gal-BSA-Cur NPs group were 1.5-fold of pure curcumin group. Meanwhile, the permeation mechanism of Gal-BSA-Cur NPs across the intestine mainly depended on the passive transport. The pharmacokinetics study in vivo suggested that the oral bioavailability of Gal-BSA-Cur NPs was improved by 1.4-fold compared with pure curcumin. CONCLUSION: All results demonstrated that Gal-BSA NPs could improve the intestinal absorption capacity and oral bioavailability of curcumin through the double absorption mechanisms of the clathrin-mediated endocytosis and the passive transport.

A SPE Method with Two MIPs in Two Steps for Improving the Selectivity of MIPs.

Molecular imprinted polymers (MIPs) have been widely applied in the separation of compounds in complex matrixes due to the high selectivity for molecular recognition. However, MIPs not only adsorb the targeted molecule but also adsorb structurally similar analogues, which leads to some loss of selectivity. In this work, for improvement of selectivity of MIPs, a novel solid-phase extraction method with two MIPs in two steps (TMIPs-TSPE) was established. As a demonstration, two MIPs were prepared by using quercetin as the template and 4-vinylypyridine (4VP) and acrylamide (AM) as representative functional monomers, respectively. The adsorption properties and kinetic characteristics of the two MIPs showed that they had a distinct adsorption capacity and adsorption mechanism, which is the basis for establishment of TMIPs-TSPE. The TMIPs-TSPE method first used one of the two MIPs as adsorbent to extract molecules from a solution mixture containing quercetin and three analogues. Then the other MIP was used to achieve a second extraction of the extracted molecules from the first step. The results showed that the unique targeted molecule quercetin was extracted, which illustrates that TMIPs-TSPE improved the specificity of the MIPs. The process of molecular recognition can be influenced by the intensity of binding sites between MIPs and molecules. Moreover, it may also depend on the spatial orientation of molecules entering the cavities of MIPs, which deserves more attention as one important property for the development of molecular imprinting. These results demonstrated that the novel TMIPs-TSPE method contributes to the improved selectivity of MIPs.