Exploring pectin-casein micelles as novel carriers for oral drug delivery of artesunate in the treatment of systemic lupus erythematosus.

The oral route of administration is considered the optimal choice for treating chronic diseases due to its convenience and non-invasiveness, which can help prevent physical and mental harm to patients undergoing long-term treatment. However, challenges such as safety, gastrointestinal stability, and bioavailability of oral drugs often limit their effectiveness. Natural biomacromolecule micelles, known for their safety, stability, biocompatibility, and diverse functions, have emerged as promising carriers for oral treatment of chronic diseases like systemic lupus erythematosus (SLE) with fat-soluble drugs. This study introduces an innovative approach by developing an oral delivery system using chemically synthesized natural biomacromolecules to load artesunate for treating SLE. By synthesizing amphiphilic polymer micelles from pectin and casein through a carbodiimide reaction, a more stable structure is achieved. The hydrophobic core of these micelles encapsulates artesunate, resulting in the formation of an oral delivery system (PC-AS) with several advantages, including high drug loading and encapsulation efficiency, small particle size, negative potential, strong stability in the gastrointestinal tract, low toxicity and side effects, strong adhesion in the small intestine, and high bioavailability. These advantages facilitate efficient absorption of artesunate in the gastrointestinal tract, leading to improved bioavailability and effective alleviation of SLE-like symptoms in MRL/lpr mice. By utilizing chemically synthesized natural macromolecular micelles for delivering artesunate in the treatment of SLE, this study overcomes the oral barriers associated with the original drug and presents a novel solution for the long-term oral treatment of chronic diseases.

Boosting Water Evaporation by Construction of Photothermal Materials with a Biomimetic Black Soil Aggregate Structure.

Solar-driven interfacial evaporation is considered an efficient way to get fresh water from seawater. However, the low evaporation rate, surface salt crystallization, and low energy collection of the photothermal evaporation layer limit its further application in an outdoor freshwater field. And the aggregate structure design of the material itself is often ignored in solar-driven water evaporation. Black soil (BS), with a unique soil aggregate structure, is rich in tubular pores, which can be used for multilevel sunlight utilization and good capillary water transport. Based on the extraordinary photothermal properties and pumping capacity of BS, a reasonable unidirectional salt-collecting device is designed, which can realize long-term collection of mineral salts and continuous evaporation of seawater and generate electric energy in the continuous evaporation. Inspired by the unique aggregate structure, the photothermal material doping of halloysite and nigrosin will simulate the generation of this aggregate structure and retain a good water transport effect while obtaining multistage utilization of sunlight. The solar-driven evaporation rate of a nigrosin-halloysite solar steam generator is 1.75 kg m-2 h-1 under 1 kW m-2 mimic solar radiation; it can achieve stable salt leaching-induced voltage generation of 240 mV. This work demonstrates not only a solar evaporator that can continuously achieve desalination but also the design strategy of BS-like aggregate photothermal materials, which promotes the development of low-cost resource recovery and energy generation for practical outdoor seawater desalination.

Remobilization characteristics and diffusion kinetic processes of sediment zinc (Zn) in a tidal reach of the Pearl River Estuary, South China.

Exploration of the remobilization mechanism of trace metals in estuarine sediments remain challenging because of dynamic hydrochemical conditions. This study integrated a chemical sequential extraction procedure (BCR), the diffusive gradient in thin films (DGT) and high-resolution dialysis techniques, and Visual MINTEQ ver.3.1 to identify the seasonal mobilization characteristics of sediment Zn within a tidal reach, South China. The mobility of sediment Zn based on the BCR procedure contradicted the results of DGT analysis. In summer, reductive dissolution of Fe/Mn oxides was the key driver of sediment Zn remobilization; during winter, cation exchange reactions facilitated the mobilization of Zn in the brackish water zone. The time-dependence ratios of DGT-labile Zn and dissolved Zn concentrations (mean: 0.34-0.81) indicated the sediment solid phase had partially sustained capacity to resupply Zn to the porewater in both seasons. Sediments generally functioned as a source of Zn in the freshwater zone with organically complexed Zn being diffusively released into the water column at rates of 0.3-15.5 µg·m-2·d-1. In the brackish water zone, the dominant Zn species were transformed into free Zn ions and Zn-inorganic complexes and migrated into sediment, with respective influxes of 18.9-70.7 µg·m-2·d-1 and 18.9-68.3 µg·m-2·d-1, which shifted to a sink of Zn.

Regulating the photophysical properties of ESIPT-based fluorescent probes by functional group substitution: a DFT/TDDFT study.

CONTEXT: In recent years, fluorescent probe technology has received more and more attention. However, the photophysical and photochemical properties of probe molecules still need to be further explored. This paper presents the excited state intramolecular proton transfer (ESIPT) processes and photophysical properties of the probe molecule 4-bromo-2-((E)-((Z)-((5-bromo-1H-indol-2-yl) methylene) hydrazono) methyl) phenol (BHPL) and its four derivatives (BHPL2, BHPL3, BHPL4, and BHPL5). Infrared spectra and geometric structure analyses revealed that introducing the -NH2 group on the benzene ring with the hydroxyl group will enhance the intramolecular hydrogen bond, which benefits the ESIPT process. Combining their absorption and fluorescence spectra, it can be concluded that BHPL2 and BHPL4 are both excellent probe candidates due to their large Stokes shift. The hole and electron and root mean square displacement analyses manifest that the fluorescence quenching of BHPL4 may be due to the intramolecular charge transfer process. Potential energy curves of BHPL and its four derivatives noted that ESIPT process of the BHPL2 is the most favorable to occur. The frontier molecular orbital and NBO analyses indicated that besides introducing electron-donating groups to reduce the energy gap and enhance fluorescence emission, introducing double electron-withdrawing groups can also achieve this effect, explaining why the energy barrier of ESIPT process for BHPL2 is lower than BHPL5. This work would provide the theoretical basis for designing novel fluorescence probes with more prominent properties. METHODS: The ground (S0) and excited (S1) state structures of all compounds were optimized by density functional theory (DFT) and time-dependent (TDDFT) method, with B3LYP/6-311+G(d,p) level, respectively. The infrared spectra and potential energy curves were simulated at the same theoretical level. The reduced density gradient scatter plots and interaction region indicator isosurfaces were drawn using Multiwfn and VMD programs. The absorption and fluorescence spectra were simulated by the TDDFT/B3PW91/6-311+G(d,p) method. All the calculations in this work are carried out in Gaussian 16 program package.

Lutein-stachyose (LS) amphiphilic oligosaccharide derivatives improve the oral bioavailability of lutein.

A new amphiphilic oligosaccharide derivative, based on lutein modification onto the OH position of stachyose with facile and mild esterification, was prepared and used to improve the oral bioavailability of lutein. The structures of lutein-stachyose derivative (LS) were confirmed by Fourier transform infrared spectroscopy and hydrogen-1 nuclear magnetic resonance, indicating that one stachyose is connected to one lutein through succinic acid. The critical micelle concentration of LS was approximately 6.86 ± 0.24 mg/mL, corresponding to the free lutein concentration of approximately 2.96 mg/mL. LS has better digestive stability and free radical scavenging ability, and it could inhibit the degradation of lutein in the gastrointestinal tract. Importantly, LS is nontoxic to cells and zebrafish embryos. In terms of oral bioavailability in rats, the AUC0-12h values of LS were 2.26 times higher than those of free lutein. Therefore, stachyose modification is a promising strategy for improving the oral bioavailability of fat-soluble lutein.

Flexible Tuning of Friction on Atomically Thin Graphene.

The tuning of flexible microscale friction is desirable for the reliability of wearable electronic devices, tactile sensors, and flexible gears. Here, the tuning of friction of atomically thin graphene on a flexible polydimethylsiloxane (PDMS) substrate was obtained with the elastic modulus using a 1H,1H,2H,2H-perfluorodecyltrichlorosilane (FDTS) self-assembly monolayers (SAMs)-modified microsphere probe with the diameter of 5 µm at the microscale. The friction can be tuned at a large scale with the difference in the elastic modulus of PDMS and thickness of graphene. The hydrophobic property of the FDTS SAMs-modified probe decreased friction by reducing interfacial adhesion and preventing the effect of capillary interaction; thus, the friction decreased with the increase in the elastic modulus of the PDMS substrate due to decreasing indentation depth and thus the interfacial contact area; and also, the enhanced out-of-plane stiffness effectively decreased the interfacial contact quality with the increase of the thickness of graphene. The flexible tuning of friction on graphene was further verified by the theoretical calculation from the aspects of the friction arising from the normal and lateral deformation around the contacting area. This work is meaningful for promoting the design and reliability of flexible micro-devices.

Whole Genome Resequencing Identifies Single-Nucleotide Polymorphism Markers of Growth and Reproduction Traits in Zhedong and Zi Crossbred Geese.

The broodiness traits of domestic geese are a bottleneck that prevents the rapid development of the goose industry. To reduce the broodiness of the Zhedong goose and thus improve it, this study hybridized it with the Zi goose, which has almost no broody behavior. Genome resequencing was performed for the purebred Zhedong goose, as well as the F2 and F3 hybrids. The results showed that the F1 hybrids displayed significant heterosis in growth traits, and their body weight was significantly greater than those of the other groups. The F2 hybrids showed significant heterosis in egg-laying traits, and the number of eggs laid was significantly greater than those of the other groups. A total of 7,979,421 single-nucleotide polymorphisms (SNPs) were obtained, and three SNPs were screened. Molecular docking results showed that SNP11 located in the gene NUDT9 altered the structure and affinity of the binding pocket. The results suggested that SNP11 is an SNP related to goose broodiness. In the future, we will use the cage breeding method to sample the same half-sib families to accurately identify SNP markers of growth and reproductive traits.

Risk Factors of Contrast Agent Intravasation With Sulfur Hexafluoride Microbubble During Hysterosalpingo-Contrast Sonography.

OBJECTIVES: To analyze the risk factors of sulfur hexafluoride microbubble contrast agent intravasation during hysterosalpingo-contrast sonography (HyCoSy), and to explore a simple prediction model by the obvious clinical history. METHODS: This was a retrospective study included 299 infertility women who had undergone HyCoSy examination from July 1, 2018 to June 31, 2019. The factors were recorded, including age, endometrial thickness, balloon length, infertility type, history of intrauterine surgery, history of pelvic surgery, and tubal patency. The method of multivariate logistic regression analysis was adopted to analyze the risk factors affecting the contrast agent intravasation, and the receiver operating characteristic curves were plotted to test their efficacy. RESULTS: Secondary infertility, a history of intrauterine surgery, thin endometrial thickness, and tubal obstruction were all risk factors of the occurrence of intravasation (P < .05). And the area under the receiver operating characteristic curves of the multifactor-combined prediction model of the intravasation was significantly larger than that of single-factor. CONCLUSIONS: Sonographers and gynecologists should be familiar with the risk factors of intravasation and select the appropriate timing of HyCoSy toward reducing the occurrence of intravasation and other complications after thoroughly explaining and communicating with the patients.

Reproductive Performance of Zi-Goose Promoted by Red Color Illumination.

The color of light affects the reproductive performance of poultry, but it is not clear what efficient illumination strategy could be adopted to improve the reproductive performance of Zi-goose. Red light can increase the average weekly egg production rate, egg production, and qualified production. It can increase the serum GnRH level and decrease the serum PRL, MT, and T4 levels. In our study, red light for 12 h increased the average weekly laying rate, average qualified egg production, and hatching rate of Zi-goose eggs, and increased the serum levels of FSH, LH, P4, E2, MT, T3, and T4. Blue light at 14 h improved the average weekly egg production rate, average egg production, and average qualified egg production, and reduce serum PRL and MT levels to ensure the improvement of reproductive performance of goose. A total of 705,714 overlapping group sequences, 471,145 transcript sequences, and 268,609 single gene sequences were obtained from 18 sequencing samples, with a total length of 323.04, 668.53, and 247.88 M, respectively. About 176,416 unigenes were annotated successfully in six databases, accounting for 65.68% of the total unigenes obtained. 2,106, 2,142, and 8,892 unigenes were identified in the hypothalamus, pituitary gland, and ovary of the birds respectively, with different expressions of light regulation. The hypothalamus, ovary, and pituitary were involved in 279, 327, and 275 KEGG (Kyoto Encyclopedia of Genes and Genomes) metabolic pathways in response to light, respectively. Through further significance analysis and differential discovery rate control, a total of five metabolic pathways were obtained which were closely related to the reproductive hormones of goose. Ten candidate genes related to the reproductive performance of goslings were selected according to the identification results of differentially expressed genes of goslings under red light and white light conditions and the genes involved in metabolic pathways significantly related to the reproductive hormones of goslings. The expression levels of GnRh-1 in the hypothalamus, GnRH-R, FSH ß and LH ß in the pituitary gland, and FSH-R and LH-R candidate genes in the ovary were higher under the 12 h red light treatment than white light. However, the expression levels of VIP, PRL, and PRL-R candidate genes in the hypothalamus, pituitary and ovary were lower under 12 h red light than under 12 h white light.

Operator's Influence on Contrast Agent Intravasation During Hysterosalpingo-Contrast Sonography: Explanation Based on a Physics Model.

Objective: To analyze the risk factors of the operators on contrast agent intravasation during hysterosalpingo-contrast sonography (HyCoSy). Methods: We retrospectively collected 399 infertile women who underwent HyCoSy by the same sonographer. These patients were divided into two groups according to the way how the assistants connected the syringe to the uterus radiography catheter to inject the contrast agent. We analyzed whether the use of different contrast bolus injection methods had any influence on the incidence of intravasation during HyCoSy. Results: There was no significant difference between the two groups with different cross-sectional areas of the syringe outflow tract in the risk variables for intravasation, but the intravasation rates of the two groups were different, 26.4% in group A and 17.1% in group B, P <0.05. The primary manifestation was that when both fallopian tubes were unobstructed, the intravasation rate of group B with smaller cross-sectional area of the outflow tract of the syringe was lower, and the difference was statistically significant. The inferences drawn from our physics model were also in line with the clinical results. Conclusion: The influence of different operators on the contrast agent intravasation rate of HyCoSy cannot be ignored. The assistants of HyCoSy examination should inject the contrast agent slowly and steady, and a needle can be used as a flow restrictor to control the flow into the uterine cavity per unit time, slow down the rising speed of intrauterine pressure, and avoid the accumulation of contrast agent in the uterine cavity, so as to reduce the intravasation caused by operator factors.

Prediction of the Effect of Methylation in the Promoter Region of ZP2 Gene on Egg Production in Jinghai Yellow Chickens.

Egg production in chickens is a quantitative trait. The aim of this study was to investigate the effect of promoter methylation of the Zona pellucida 2 (ZP2) gene on egg production. Real-time fluorescence quantification showed that the expression of the ZP2 gene in the ovaries of 300-day-old Jinghai yellow chickens in the high-laying group was significantly higher than that in the low-laying group (p < 0.01). A series of deletion fragments of the ZP2 gene promoter in Jinghai yellow chickens had different promoter activities in DF-1 cells, and the core region of the ZP2 gene promoter was found to be between −1552 and −1348. Four CpG islands in the promoter region of the ZP2 gene were detected by software prediction. The overall degree of methylation of the ZP2-1 amplified fragment was negatively correlated with mRNA expression to some extent (R = −0.197); the overall degree of methylation of the ZP2-2 amplified fragment was also negatively correlated with mRNA expression to some extent (R = −0.264), in which the methylation of methylcytosine (mC)-9, mC-20, and mC-21 sites was significantly negatively correlated with mRNA expression (p < 0.05). In addition, the mC-20 and mC-21 sites are located on the Sp1 transcription factor binding site, and it is speculated that these two sites may be the main sites for regulating transcription. In summary, the methylation sites mC-20 and mC-21 of the ZP2 gene may inhibit the binding of Sp1 and DNA, affect the transcription of the ZP2 gene, and then affect the number of eggs produced by the Jinghai yellow chickens.

[Retracted] MicroRNA­655 inhibits cell proliferation and invasion in epithelial ovarian cancer by directly targeting vascular endothelial growth factor.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the cell invasion assay data shown in Figs. 2C and 4C were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 18: 1878­1884, 2018; DOI: 10.3892/mmr.2018.9090].

Theoretical study on the optical properties of an ESIPT-based fluorescent probe for phosgene.

A fluorescent probe Pi with the excited-state intramolecular proton transfer (ESIPT) properties was synthesized and used to detect the phosgene in solution and gas phases. However, the detection mechanism of the fluorescent probe needs to be further studied. Herein, the density functional theory (DFT) and time-dependent density functional theory (TD-DFT) methods were adopted to explore the molecular structures and electronic spectra properties of probe and its product Pio after reacting with phosgene. Through analysis for molecular structure parameters and infrared vibrations accompanied with the hydrogen bond of Pi, it is confirmed that the intramolecular hydrogen bond of Pi is enhanced under light excitation, which illustrates the occurrence of ESIPT reaction combined with the scanned potential energy curves. It can be seen from the simulated spectra that Pi shows double fluorescence through ESIPT process, while the fluorescent product Pio exhibits the single fluorescence due to the disappearance of intramolecular hydrogen bond. Through the study on the structure and optical properties of Pi and Pio, it can be helpful to deeply understand the intrinsic mechanism of the detection of phosgene by the Pi molecule probe, which also supplies a reference to the further study about the fluorescence probe.

Antioxidative Activity Evaluation of High Purity and Micronized Tartary Buckwheat Flavonoids Prepared by Antisolvent Recrystallization.

Tartary buckwheat, a healthy food, is associated with a reduced risk of certain human chronic diseases. However, the bioactive component flavonoids in Tartary buckwheat have poor solubility and low absorption in vivo. To improve these points, 60.00% Tartary buckwheat total flavonoids (TFs) were obtained by ethanol refluxing method, which were purified and micronized by antisolvent recrystallization (ASR) using methanol as a solvent and deionized water as an antisolvent. By using High Performance Liquid Chromatography (HPLC) and electrospray ionized mass spectrometry (ESI-MS), the main flavonoid in pure flavonoids (PF) were rutin (RU), kaempferol-3-O-rutinoside (KA) and quercetin (QU); the content of TF is 99.81% after purification. It is more worthy of our attention that micronized flavonoids contribute more to antioxidant activity because of good solubility. These results provide a theoretical reference for the micronization of other flavonoids.

Study on the preparation and activity of intelligent response poly(lactic-co-glycolic acid)-ss-polyethylene glycol copolymer micelles.

Amphiphilic polymer micellar carriers are the most commonly used nanocarriers for oral delivery of hydrophobic drugs because their hydrophilic shell can avoid the recognition of the reticuloendothelial system (RES), has excellent drug-carrying capacity, and protect the drug from inactivation in the gastrointestinal fluid. The polymer micelle shell can enter cancer cells by endocytosis, and autophagy in cells, degradation by lysosomal pathway, so as to release drugs, prolong the circulation time of drugs in vivo, and then achieve the effect of drug sustained release. In this study, the glutathione-responsive PLGA-ss-PEG loaded paclitaxel (PTX) micelles (PLGA-ss-PEG-PTX) were developed for anticancer therapy. With its long-term circulation and EPR (enhanced permeability and retention) effect, and the micelle had disulfide bond, which could be used as the recognition group of tumor microenvironment, so that the PLGA-ss-PEG-PTX could specifically accumulate at the tumor site, so as to produce better anti-tumor effect. The PLGA-ss-PEG-PTX was formulated by the emulsification method in this study. The drug loading was about 21.54%, the entrapment efficiency was about 94.2%, and the particle size range was about 90 nm with narrow particle size distribution. Cytotoxicity and embryonic toxicity experiments were carried out using mouse lung cancer cells (LLC) and zebrafish fertilized eggs. It was proved that the low concentration of blank micelles had little cytotoxicity, but high concentration of blank micelles had adverse effects on zebrafish embryonic development, resulting in embryonic malformation. The uptake of drugs by cancer cells was studied by a high connotation cell imaging analysis system. The experiments showed that the drug molecules encapsulated in micelles could achieve higher uptake by cells compared with free drug molecules. In addition, in the in vivo evaluation experiment of drugs, the PLGA-ss-PEG-PTX could significantly enhance the therapeutic effect of the PTX, improve its water solubility, and improve its oral bioavailability.

A DFT study on the structure activity relationship of the natural xanthotoxin-based pharmaceutical cocrystals.

In this work, the pharmaceutical cocrystals xanthotoxin-para-aminobenzoic acid (XT-PABA) and xanthotoxin-oxalic acid (XT-OA) were systematically investigated in the gas and water phases by using the quantum chemical approach. The weak intermolecular interactions have been estimated and the O1…H4 (O1…H5) intermolecular hydrogen bond (IHB) with moderate intensity and partial covalent natures was confirmed based on the computed structural parameters, topology analysis, and reduced density gradient (RDG) isosurfaces. The electrophilic and nucleophilic reactivities of different positions associated with intermolecular interactions in XT, PABA, and OA were predicted by plotting the molecular electrostatic potential (MESP) diagrams. The calculated natural bond orbital (NBO) population analysis has quantitatively unveiled the intrinsic reason for the variations in weak intermolecular interactions within XT-PABA and XT-OA cocrystals, from the gas phase to the water phase. Besides, the frontier molecular orbitals (FMOs), Fukui function, and various global reactivity descriptors were computed to measure the chemical reactivity of all the investigated molecular systems. The XT-PABA and XT-OA cocrystals explored in this work could be regarded as valuable exemplar systems to design and synthesize the high-efficiency pharmaceutical cocrystals in the experiment.

Artemisinin hydroxypropyl-ß-cyclodextrin inclusion complex loaded with porous starch for enhanced bioavailability.

The current work aimed to enhance the oral bioavailability of water-insoluble drug Artemisinin (ART) by the inclusion of ART with hydroxypropyl-ß-cyclodextrin (HP-ß-CD) and then loaded with porous starch (PS). The preparation conditions of ART HP-ß-CD inclusion complex loaded with PS (AHPS) were optimized according to drug loading (DL) and entrapment efficiency (EE). The properties of AHPS were characterized by optical and thermodynamic methods. ART was linked by hydrogen bond to HP-ß-CD to form hydrophilic supramolecules, which are loaded into PS under the action of hydrogen bond. The maximum DL and EE of AHPS were about 16.51% and 67.26%, respectively. Then we investigated the physicochemical properties and antimalarial activity of AHPS. The solubility and bioavailability of AHPS at 48 h were higher than ART and market ART piperaquine tablets (APT), and showed better antimalarial activity in vitro and vivo. It provides a new idea for the development and application of fat-soluble drug.

IFI16 induces inflammation in hepatitis B virus-associated glomerulonephritis by regulating the Caspase-1/ IL-1 ß pathway.

AIMS AND BACKGROUND: IFI16 plays an important role in innate immunity against invasive microbial infection by sensing double-stranded DNA viruses due to caspase-1-dependent inflammasome activation and subsequent maturation and secretion of IL-1ß. However, the role of IFI16 in regulating the immune response to viruses in Hepatitis B Virus-Associated Glomerulonephritis (HBV-GN), especially in sensing hepatitis B virus (HBV), has not been determined. In this study, we investigated the inflammatory role of IFI16 in HBV-GN. METHODS: A total 75 kidney tissue including 50 HBV-GN and 25 chronic glomerulonephritis (CCN) were collected to determine the expression of IFI16, Caspase-1 and IL-1ß using immunohistochemistry (IHC), then the correlation between them was analyzed. In vitro, the primary human glomerular mesangial (HGM) cells and HEK-293 T cell lines were used in this study. The cell lines were both co-transfected with HBVDNA and overexpression or silencing IFI16. Quantitative Real-time PCR and western blotting were used to determine the expression of IFI16, Caspase-1 and IL-1ß. RESULTS: IFI16 expression in HBV-GN biopsies (80.0%) was significantly higher than in CGN (24.0%) and positively correlated with HBVDNA,caspase-1 and IL-1ß expression in HBV-GN. Meanwhile, over expression of IFI16 increased caspase-1 and IL-1ß expression in HBV-infected HGM and HEK-293 T cell lines, knockdown of IFI16 mRNA by siRNA resulted in downregulation of the caspase-1 and IL-1ß expression in both cell lines. CONCLUSIONS: The elevation of IFI16 during HBV infection or replication may contribute to renal damage due to inflammation, thus providing a putative therapeutic target and a new avenue for researching the pathogenesis of HBV-GN.

Preparation and characterisation of ecdysterone/hydroxypropyl-Β-cyclodextrin inclusion complex with enhanced oral and transdermal bioavailability.

To prepare ecdysterone (ES)/hydroxypropyl-ß-cyclodextrin (HP-ß-CD) inclusion complex, thus improving the water solubility and bioavailability of ES. Phase-solubility study was performed to study the mass ratio of ES and HP-ß-CD. Then, the ES/HP-ß-CD inclusion complex was prepared by the solvent evaporation method, and its physicochemical properties were characterised using the SEM, DSC, XRD, 1HNMR and FT-IR. In addition, in vitro dissolution and bioavailability (oral and transdermal) experiments were also conducted. The inclusion complex was formed with ES and HP-ß-CD at the mass ratio of 1:1. ES existed in an amorphous form in the inclusion complex. The equilibrium solubility of ES/HP-ß-CD inclusion complex in SGF (simulated gastric fluid) and SIF (simulated intestinal fluid) was 50.6 ± 0.11 mg/mL and 75.9 ± 0.38 mg/mL in SGF and SIF, which was 5.93 and 9.96 times higher than that of free ES, respectively. The ES/HP-ß-CD inclusion complex had better dissolution ability and transdermal permeability than the free ES. The oral bioavailability and the transdermal bioavailability were respectively increased by 2.97 times and 1.92 times compared with the free ES. These data suggest that the ES/HP-ß-CD inclusion complex can be developed as potential pharmaceutical product for future clinical applications.