Study on the interaction between 2,6-dihydroxybenzoic acid nicotine salt and human serum albumin by multi-spectroscopy and molecular dynamics simulation.

As a new form of nicotine introduction for novel tobacco products, the interaction of nicotine salt with biological macromolecules may differ from that of free nicotine and thus affect its transport and distribution in vivo. Hence, the mechanism underlying the interaction between 2,6-dihydroxybenzoic acid nicotine salt (DBN) and human serum albumin (HSA) was investigated by multi-spectroscopy, molecular docking, and dynamic simulation. Experiments on steady-state fluorescence and fluorescence lifetime revealed that the quenching mechanism of DBN and HSA was dynamic quenching, and binding constant was in the order of 10^4 L mol-1. Thermodynamic parameters exhibited that the binding was a spontaneous process with hydrophobic forces as the main driving force. Fluorescence competition experiments revealed that DBN bound to site I of HSA IIA subdomain. According to the results of synchronous fluorescence, 3D fluorescence, FT-IR spectroscopy, circular dichroism (CD) spectroscopy, and molecular dynamics (MD) simulation, DBN did not affect the basic skeleton structure of HSA but changed the microenvironment around the amino acid residues. Computer simulations positively corroborated the experimental results. Moreover, DBN decreased the surface hydrophobicity and weakened the esterase-like activity of HSA, leading to the impaired function of the latter. This work provides important information for studying the interaction between DBN as a nicotine substitute and biological macromolecules and contributes to the further development and application of DBN.

Self-assembled phospholipid-based mixed micelles for improving the solubility, bioavailability and anticancer activity of lenvatinib.

The clinical efficacy of lenvatinib (LFT) is limited by its poor aqueous solubility and low bioavailability. In this work, LFT-loaded soy phospholipid and sodium glycocholate mixed micelles (LFT-MMs) were prepared through classical co-precipitation. And it was served as an oral administration to address these shortcomings. The preparation conditions were optimized by single-factor experiments. The mass ratio of PC, SGC and LFT, and the species of dispersing media were proved to be decisive factors in controlling the properties of LFT-MMs. The optimal LFT-MMs presented prominent enhancement (500-fold) in LFT solubility, high encapsulation efficiency (87.6 %) as well as suitable stability (>1 month at 4 °C). The biocompatibility of LFT-MMs was estimated by in vitro serum stability measurement and hemolysis test. It showed that serum proteins hardly adhered to the surface of LFT-MMs, and insignificant hemolytic rate (<0.5 %) was observed at the micelles concentration below 1 mg/mL. Cytotoxicity test (MTT assay) was carried out to judge the in vitro antitumor activity. LFT-MMs showed an enhanced inhibitory activity against two main kinds of differentiated thyroid cancer cells over LFT and LFT Mesylate. To estimate the in vivo oral bioavailability of LFT-MMs, SD rats were used as animal model. Notably, the relative bioavailability of LFT-MMs compared with the original form of LFT was 176.7 %. These superior characteristics indicated that the mixed micelles are promising water-soluble formulations suitable for LFT oral delivery.

Multispectroscopic and docking studies on the binding of chlorogenic acid isomers to human serum albumin: Effects of esteryl position on affinity.

Structural differences among various dietary polyphenols affect their absorption, metabolism, and bioactivities. In this work, chlorogenic acid (CA) and its two positional isomers, neochlorogenic acid (NCA) and cryptochlorogenic acid (CCA), were investigated for their binding reactions with human serum albumin (HSA) using fluorescence, ultraviolet-visible, Fourier transform infrared and circular dichroism spectroscopies, as well as molecular docking. All three isomers were bound to HSA at Sudlow's site I and affected the protein secondary structure. CCA presented the strongest ability of hydrogen-bond formation, and both CA and NCA generated more electrostatic interactions with HSA. The albumin-binding capacity of these compounds decreased in the order CCA>NCA>CA. The compound with 4-esteryl structure showed higher binding affinity and larger conformational changes to HSA than that with 3- or 5-esteryl structures. These comparative studies on structure-affinity relationship contributed to the structural modification and design of phenolic food additives or new polyphenol-like drugs.