High-cholesterol diet in combination with hydroxypropyl-beta-cyclodextrin induces NASH-like disorders in the liver of rats.

Non-alcoholic fatty liver disease (NAFLD) is a general term for fatty liver disease not caused by viruses or alcohol. Fibrotic hepatitis, cirrhosis, and hepatocellular carcinoma can develop. The recent increase in NAFLD incidence worldwide has stimulated drug development efforts. However, there is still no approved treatment. This may be due in part to the fact that non-alcoholic steatohepatitis (NASH) pathogenesis is very complex, and its mechanisms are not well understood. Studies with animals are very important for understanding the pathogenesis. Due to the close association between the establishment of human NASH pathology and metabolic syndrome, several animal models have been reported, especially in the context of overnutrition. In this study, we investigated the induction of NASH-like pathology by enhancing cholesterol absorption through treatment with hydroxypropyl-beta-cyclodextrin (CDX). Female Sprague-Dawley rats were fed a normal diet with normal water (control group); a high-fat (60 kcal%), cholesterol (1.25 %), and cholic acid (0.5 %) diet with normal water (HFCC group); or HFCC diet with 2 % CDX water (HFCC+CDX group) for 16 weeks. Compared to the control group, the HFCC and HFCC+CDX groups showed increased blood levels of total cholesterol, aspartate aminotransferase, and alanine aminotransferase. At autopsy, parameters related to hepatic lipid synthesis, oxidative stress, inflammation, and fibrosis were elevated, suggesting the development of NAFLD/NASH. Elevated levels of endoplasmic reticulum stress-related genes were evident in the HFCC+CDX group. In the novel rat model, excessive cholesterol intake and accelerated absorption contributed to NAFLD/NASH pathogenesis.

Investigation of 2-Hydroxypropyl-ß-Cyclodextrin Treatment in a Neuronal-Like Cell Model of Niemann-Pick Type C Using Quantitative Proteomics.

Niemann-Pick, type C (NPC) is a fatal, neurovisceral lysosomal storage disorder with progressive neurodegeneration and no FDA-approved therapy. Significant efforts have been focused on the development of therapeutic options, and 2-hydroxypropyl-ß-cyclodextrin (HP-b-CD) has emerged as a promising candidate. In cell culture, HP-b-CD ameliorates cholesterol storage in endo/lysosomes, a hallmark of the disorder. Furthermore, in animal studies, treatment with HP-b-CD delays neurodegeneration and extends lifespan. While HP-b-CD has been promising in vitro and in vivo, a clear understanding of the mechanism(s) of action is lacking. Utilizing a neuron-like cell culture model of SH-SY5Y differentiated cells and U18666A to induce the NPC phenotype, we report here a large-scale mass-spectrometry-based proteomic study to evaluate proteome changes upon treatment with these small molecules. In this study, we show that differentiated SH-SY5Y cells display morphological changes representative of neuronal-like cells along with increased levels of proliferation markers. Inhibition of the NPC cholesterol transporter 1 protein by U18666A resulted in increased levels of known NPC markers including SCARB2/LIMP2 and LAMP2. Finally, investigation of HP-b-CD treatment was performed where we observe that, although HP-b-CD reduces cholesterol storage, levels of NPC1 and NPC2 are not normalized to control levels. This finding further supports the need for a proteostasis strategy for NPC drug development. Moreover, proteins that were dysregulated in the U18666A model of NPC and normalized to control levels suggest that HP-b-CD promotes exocytosis in this neuron-like model. Utilizing state of the art mass spectrometry analysis, these data demonstrate newly reported changes with pharmacological perturbations related to NPC disease and provide insight into the mechanisms of HP-b-CD as a potential therapeutic.

Cyclodextrins applied to the treatment of lysosomal storage disorders.

Cyclodextrin (CD), a cyclic oligosaccharide, is a pharmaceutical additive that improves the solubility of hydrophobic compounds. Recent research has focused on the potential active pharmaceutical abilities of CD. Lysosomal storage diseases are inherited metabolic diseases characterized by lysosomal dysfunction and abnormal lipid storage. Niemann-Pick disease type C (NPC) is caused by mutations in cholesterol transporter genes (NPC1, NPC2) and is characterized by cholesterol accumulation in lysosomes. A biocompatible cholesterol solubilizer 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD) was recently used in NPC patients for compassionate use and in clinical trials. HP-ß-CD is an attractive drug candidate for NPC; however, its adverse effects, such as ototoxicity, should be solved. In this review, we discuss the current use of HP-ß-CD in basic and clinical research and discuss alternative CD derivatives that may outperform HP-ß-CD, which should be considered for clinical use. The potential of CD therapy for the treatment of other lysosomal storage diseases is also discussed.

Mitigating RANKL-induced cholesterol overload in macrophages with ß-cyclodextrin-threaded polyrotaxanes suppresses osteoclastogenesis.

Free cholesterol acts as an endogenous agonist for estrogen-related receptor α (ERRα), a nuclear receptor that regulates osteoclastogenesis. Because stimulation of macrophages with receptor activator of nuclear factor κB ligand (RANKL) induces an overload of free cholesterol and activates ERRα, we hypothesized that direct removal of cellular cholesterol would suppress osteoclastogenesis. In this study, the effect of 2-hydroxypropyl ß-cyclodextrin (HP-ß-CD), a highly water-soluble cyclic glucopyranose, and ß-CD-threaded polyrotaxanes (PRXs), supramolecular polymers designed to release threaded ß-CDs in acidic lysosomes, on RANKL-induced cholesterol overload and osteoclast differentiation of murine macrophage-like RAW264.7 cells were investigated. PRXs suppressed RANKL-induced cholesterol overload. Additionally, RANKL-induced osteoclast differentiation of RAW264.7 cells was inhibited by PRXs. In contrast, HP-ß-CD did not reduce cholesterol levels or inhibit osteoclast differentiation in RAW264.7 cells. Gene expression analysis of osteoclast markers suggested that PRXs suppress only the early stage of osteoclast differentiation, as PRXs cannot be internalized into multinucleated osteoclasts. However, modification of PRXs with cell-penetrating peptides facilitated their cellular uptake into multinucleated osteoclasts and inhibited osteoclast maturation. Thus, PRXs are promising candidates for inhibiting osteoclast differentiation by suppressing cholesterol overload and may be useful for treating osteoporosis or other bone defects caused by the overactivity of osteoclasts.

Effect of Different Absorption Enhancers on the Nasal Absorption of Nalmefene Hydrochloride.

The purpose of this work is to explore the effects of novel absorption enhancers on the nasal absorption of nalmefene hydrochloride (NMF). First, the influence of absorption enhancers with different concentrations and types and drug concentrations on the nasal absorption of NMF was investigated in vivo in rats. The absorption enhancers studied include n-dodecyl-ß-D-maltoside (DDM), hydroxypropyl-ß-cyclodextrin (HP-ß-CD), and polyethylene glycol (15)-hydroxy Stearate (Solutol®HS15). At the same time, the in situ toad palate model and rat nasal mucosa model were used to assess the cilia toxicity. The results showed that all the absorption enhancers investigated significantly promote the nasal absorption of NMF, but with different degrees and trends. Among them, the 0.5% (w/v) DDM had the strongest enhancement effect, followed by 0.5% (w/v) Solutol®HS15, 0.25% (w/v) DDM, 0.25% (w/v) Solutol®HS15, 0.1% (w/v) Solutol®HS15, 0.1% (w/v) DDM, and 0.25% (w/v) HP-ß-CD, with absolute bioavailability of 76.49%, 72.14%, 71.00%, 69.46%, 60.41%, 59.42%, and 55.18%, respectively. All absorption enhancers exhibited good safety profiles in nasal ciliary toxicity tests. From the perspective of enhancing effect and safety, we considered DDM to be a promising nasal absorption enhancer. And in addition to DDM, Solutol®HS15 can also promote intranasal absorption of NMF, which will provide another option for the development of nalmefene hydrochloride nasal spray.

Insulin Complexation with Cyclodextrins-A Molecular Modeling Approach.

Around 5% of the population of the world is affected with the disease called diabetes mellitus. The main medication of the diabetes is the insulin; the active form is the insulin monomer, which is an instable molecule, because the long storage time, or the high temperature, can cause the monomer insulin to adapt an alternative fold, rich in ß-sheets, which is pharmaceutically inactive. The aim of this study is to form different insulin complexes with all the cyclodextrin used for pharmaceutical excipients (native cyclodextrin, methyl, hydroxyethyl, hydroxypropyl and sulfobutylether substituted ß-cyclodextrin), in silico condition, with the AutoDock molecular modeling program, to determine the best type of cyclodextrin or cyclodextrin derivate to form a complex with an insulin monomer, to predict the molar ratio, the conformation of the complex, and the intermolecular hydrogen bonds formed between the cyclodextrin and the insulin. From the results calculated by the AutoDock program it can be predicted that insulin can make a stable complex with 5-7 molecules of hydroxypropyl-ß-cyclodextrin or sulfobutylether-ß-cyclodextrin, and by forming a complex potentially can prevent or delay the amyloid fibrillation of the insulin and increase the stability of the molecule.

Intradermal injection of icariin-HP-ß-cyclodextrin improved traumatic brain injury via the trigeminal epineurium-brain dura pathway.

The lower bioavailability after oral administration limited icariin applications in central nervous system. Icariin/HP-ß-cyclodextrin (HP-ß-CD) inclusion complex was prepared for acute severe opening traumatic brain injury (TBI) via facial intradermal (i.d.) in the mystacial pad. After fluid percussion-induced TBI, icariin/HP-ß-CD at 0.4 mg/kg i.d. preserved more neurons and oligodendrocytes than intranasal injection (i.n.) or intravenous injection via tail vein (i.v.) and decreased microglia and astrocyte activation. Icariin/HP-ß-CD i.d. reduced apoptosis in cortical penumbra while i.n. and i.v. showed weak or no effects. Icariin/HP-ß-CD i.d. reduced Evans blue leakage and altered CD34, ZO-1, Claudin-5, and beta-catenin expression after TBI. Moreover, icariin/HP-ß-CD promoted human umbilical vein endothelial cells proliferation. Thus, Icariin/HP-ß-CD i.d. improved TBI, including blood-brain barrier opening. Fluorescein 5-isothiocyanate (FITC) and 3,3'-Dioctadecyloxacarbocyanine perchlorate (DiOC18(3)) mimic HP-ß-CD and icariin respectively. FITC and DiOC18(3) were similarly delivered to trigeminal epineurium, perineurium and perivascular spaces or tissues, caudal dura mater, and scattered in trigeminal fasciculus, indicating that icariin/HP-ß-CD was delivered to the brain via trigeminal nerve-dura mater-brain pathways. In sum, intradermal injection in mystacial pad might deliver icariin/HP-ß-CD to the brain and icariin/HP-ß-CD improved acute severe opening TBI.

Bioaugmentation treatment of polycyclic aromatic hydrocarbon-polluted soil in a slurry bioreactor with a bacterial consortium and hydroxypropyl-ß-cyclodextrin.

The aim of the study was to verify the effect of bioaugmentation by the bacterial consortium YS with hydroxypropyl-ß-cyclodextrin (HPCD) in a soil slurry. The bacterial consortium YS was enriched from a petroleum-polluted soil using pyrene as sole carbon resource. After 3 weeks, the degradation rate of phenanthrene in CK increased from 22.58% to 55.23 and 78.21% in bioaugmentation (B) and HPCD + bioaugmentation (MB) respectively. The degradation rate of pyrene in CK increased from 17.33% to 51.10% and 60.32% in B and MB respectively in the slurry. The augmented YS persisted in the slurry as monitored by 16S rRNA gene high-throughput sequencing and outcompeted some indigenous bacteria. Enhanced polycyclic aromatic hydrocarbon (PAH) degradation was observed in the addition of HPCD due to the enhanced bioavailability of phenanthrene and pyrene. Additionally, the amount of PAH-degrading bacteria and enzymatic activity in bioaugmentation with HPCD were higher than that in the CK group. The results indicated that bioaugmentation with a bacterial consortium and HPCD is an environmentally friendly method for the bioremediation of PAH-polluted soil.

Parkinson's Disease Phenotypes in Patient Neuronal Cultures and Brain Organoids Improved by 2-Hydroxypropyl-ß-Cyclodextrin Treatment.

BACKGROUND: The etiology of Parkinson's disease (PD) is only partially understood despite the fact that environmental causes, risk factors, and specific gene mutations are contributors to the disease. Biallelic mutations in the phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1) gene involved in mitochondrial homeostasis, vesicle trafficking, and autophagy are sufficient to cause PD. OBJECTIVES: We sought to evaluate the difference between controls' and PINK1 patients' derived neurons in their transition from neuroepithelial stem cells to neurons, allowing us to identify potential pathways to target with repurposed compounds. METHODS: Using two-dimensional and three-dimensional models of patients' derived neurons we recapitulated PD-related phenotypes. We introduced the usage of midbrain organoids for testing compounds. Using Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein 9 (Cas9), we corrected the point mutations of three patients' derived cells. We evaluated the effect of the selected compound in a mouse model. RESULTS: PD patient-derived cells presented differences in their energetic profile, imbalanced proliferation, apoptosis, mitophagy, and a reduced differentiation efficiency to tyrosine hydroxylase positive (TH+) neurons compared to controls' cells. Correction of a patient's point mutation ameliorated the metabolic properties and neuronal firing rates as well as reversing the differentiation phenotype, and reducing the increased astrocytic levels. Treatment with 2-hydroxypropyl-ß-cyclodextrin increased the autophagy and mitophagy capacity of neurons concomitant with an improved dopaminergic differentiation of patient-specific neurons in midbrain organoids and ameliorated neurotoxicity in a mouse model. CONCLUSION: We show that treatment with a repurposed compound is sufficient for restoring the impaired dopaminergic differentiation of PD patient-derived cells. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Universal capability of 3-ketosteroid Δ1-dehydrogenases to catalyze Δ1-dehydrogenation of C17-substituted steroids.

BACKGROUND: 3-Ketosteroid Δ1-dehydrogenases (KSTDs) are the enzymes involved in microbial cholesterol degradation and modification of steroids. They catalyze dehydrogenation between C1 and C2 atoms in ring A of the polycyclic structure of 3-ketosteroids. KSTDs substrate spectrum is broad, even though most of them prefer steroids with small substituents at the C17 atom. The investigation of the KSTD's substrate specificity is hindered by the poor solubility of the hydrophobic steroids in aqueous solutions. In this paper, we used 2-hydroxpropyl-ß-cyclodextrin (HBC) as a solubilizing agent in a study of the KSTDs steady-state kinetics and demonstrated that substrate bioavailability has a pivotal impact on enzyme specificity. RESULTS: Molecular dynamics simulations on KSTD1 from Rhodococcus erythropolis indicated no difference in ΔGbind between the native substrate, androst-4-en-3,17-dione (AD; - 8.02 kcal/mol), and more complex steroids such as cholest-4-en-3-one (- 8.40 kcal/mol) or diosgenone (- 6.17 kcal/mol). No structural obstacle for binding of the extended substrates was also observed. Following this observation, our kinetic studies conducted in the presence of HBC confirmed KSTD1 activity towards both types of steroids. We have compared the substrate specificity of KSTD1 to the other enzyme known for its activity with cholest-4-en-3-one, KSTD from Sterolibacterium denitrificans (AcmB). The addition of solubilizing agent caused AcmB to exhibit a higher affinity to cholest-4-en-3-one (Ping-Pong bi bi KmA = 23.7 µM) than to AD (KmA = 529.2 µM), a supposedly native substrate of the enzyme. Moreover, we have isolated AcmB isoenzyme (AcmB2) and showed that conversion of AD and cholest-4-en-3-one proceeds at a similar rate. We demonstrated also that the apparent specificity constant of AcmB for cholest-4-en-3-one (kcat/KmA = 9.25∙106 M-1 s-1) is almost 20 times higher than measured for KSTD1 (kcat/KmA = 4.71∙105 M-1 s-1). CONCLUSIONS: We confirmed the existence of AcmB preference for a substrate with an undegraded isooctyl chain. However, we showed that KSTD1 which was reported to be inactive with such substrates can catalyze the reaction if the solubility problem is addressed.

The Budesonide-Hydroxypropyl-ß-Cyclodextrin Complex Attenuates ROS Generation, IL-8 Release and Cell Death Induced by Oxidant and Inflammatory Stress. Study on A549 and A-THP-1 Cells.

Synthetic glucocorticoids such as budesonide (BUD) are potent anti-inflammatory drugs commonly used to treat patients suffering from chronic inflammatory diseases. A previous animal study reported a higher anti-inflammatory activity with a 2-hydroxypropyl-ß-cyclodextrin (HPßCD)-based formulation of BUD (BUD:HPßCD). This study investigated, on cellular models (A549 and A-THP-1), the effect of BUD:HPßD in comparison with BUD and HPßCD on the effects induced by oxidative and inflammatory stress as well as the role of cholesterol. We demonstrated the protective effect afforded by BUD:HPßCD against cytotoxicity and ROS generation induced by oxidative and inflammatory stress. The effect observed for BUD:HPßCD was comparable to that observed with HPßCD with no major effect of cholesterol content. We also demonstrated (i) the involvement of the canonical molecular pathway including ROS generation, a decrease in PI3K/Akt activation, and decrease in phosphorylated/unphosphorylated HDAC2 in the effect induced by BUD:HPßCD, (ii) the maintenance of IL-8 decrease with BUD:HPßCD, and (iii) the absence of improvement in glucocorticoid insensitivity with BUD:HPßCD in comparison with BUD, in conditions where HDAC2 was inhibited. Resulting from HPßCD antioxidant and anticytotoxic potential and protective capacity against ROS-induced PI3K/Akt signaling and HDAC2 inhibition, BUD:HPßCD might be more beneficial than BUD alone in a context of concomitant oxidative and inflammatory stress.

A recycled batch biotransformation strategy for 22-hydroxy-23,24-bisnorchol-4-ene-3-one production from high concentration of phytosterols by mycobacterial resting cells.

OBJECTIVES: To realize a practical technology for recycling both cyclodextrin and resting-cells at the same time in phytosterol biotransformation using mycobacterial resting cells. RESULTS: In order to produce 22-hydroxy-23,24-bisnorchol-4-ene-3-one (HBC) efficiently and low-costly, a recycled phytosterols (PS) biotransformation process using mycobacterial resting cells was developed. By optimizing the ratio of hydroxypropyl-ß-cyclodextrin (HP-ß-CD) and PS to 1:1 (w/w), most products crystallized during the biotransformation process. So, the HBC was easily separated by low-speed (900×g) centrifugation with yield of 92%. The resting cells, HP-ß-CD and the residual products and substrates left in the reaction system were reused for another bioconversion cycle after PS supplement. Three continuous cycles were achieved without the supplement of cells and HP-ß-CD. In each batch, 80 g L-1 of PS was transformed to HBC with the space-time yield of HBC of 8.9-12.8 g L-1 day-1. CONCLUSIONS: This strategy reduced the cost of HBC production and simplified the purification process.

The Sterol Carrier Hydroxypropyl-ß-Cyclodextrin Enhances the Metabolism of Phytosterols by Mycobacterium neoaurum.

Androst-4-ene-3,17-dione (AD) and androst-1,4-diene-3,17-dione (ADD) are valuable steroid pharmaceutical intermediates obtained by soybean phytosterol biotransformation by Mycobacterium Cyclodextrins (CDs) are generally believed to be carriers for phytosterol delivery and can improve the production of AD and ADD due to their effects on steroid solubilization and alteration in cell wall permeability for steroids. To better understand the mechanisms of CD promotion, we performed proteomic quantification of the effects of hydroxypropyl-ß-CD (HP-ß-CD) on phytosterol metabolism in Mycobacterium neoaurum TCCC 11978 C2. Perturbations are observed in steroid catabolism and glucose metabolism by adding HP-ß-CD in a phytosterol bioconversion system. AD and ADD, as metabolic products of phytosterol, are toxic to cells, with inhibited cell growth and biocatalytic activity. Treatment of mycobacteria with HP-ß-CD relieves the inhibitory effect of AD(D) on the electron transfer chain and cell growth. These results demonstrate the positive relationship between HP-ß-CD and phytosterol metabolism and give insight into the complex functions of CDs as mediators of the regulation of sterol metabolism.IMPORTANCE Phytosterols from soybean are low-cost by-products of soybean oil production and, owing to their good bioavailability in mycobacteria, are preferred as the substrates for steroid drug production via biotransformation by Mycobacterium However, the low level of production of steroid hormone drugs due to the low aqueous solubility (below 0.1 mmol/liter) of phytosterols limits the commercial use of sterol-transformed strains. To improve the bioconversion of steroids, cyclodextrins (CDs) are generally used as an effective carrier for the delivery of hydrophobic steroids to the bacterium. CDs improve the biotransformation of steroids due to their effects on steroid solubilization and alterations in cell wall permeability for steroids. However, studies have rarely reported the effects of CDs on cell metabolic pathways related to sterols. In this study, the effects of hydroxypropyl-ß-CD (HP-ß-CD) on the expression of enzymes related to steroid catabolic pathways in Mycobacterium neoaurum were systematically investigated. These findings will improve our understanding of the complex functions of CDs in the regulation of sterol metabolism and guide the application of CDs to sterol production.

Synthesis and biological evaluation of ß-lapachone and nor-ß-lapachone complexes with 2-hydroxypropyl-ß-cyclodextrin as trypanocidal agents.

We study ßLAP and its derivative nor-ß-Lapachone (NßL) complexes with 2-hydroxypropyl-ß-cyclodextrin to increase the solubility and bioavailability. The formation of true inclusion complexes between ßLAP or NßL in 2-HP-ß-CD in solid solution was characterization by FT-IR, DSC, powder X-ray was and was confirmed by one- and two-dimensional 1H NMR experiments. Additionally, the biological activities of ßLAP, NßL, ICßLAP, and ICNßL were investigated through trypanocidal assays with T. cruzi and cytotoxicity studies with mouse peritoneal macrophages. Originally, we tested these complexes against T. cruzi viability and observed higher biological activities and lower cytotoxicity when compared to ßLAP and NßL. Thus, the complexation of ßLAP and NßL with 2-HP-ß-CD increases the drug solubility, in addition vectorization was observed, increasing the biological activity against epimastigotes and trypomastigotes T. cruzi forms. Reduced the toxicity of the compounds against mammalian cells. In addition, the selectivity indices higher of the inclusion complexes comparing to substance free and those of benznidazole.

A Renal-Clearable Macromolecular Reporter for Near-Infrared Fluorescence Imaging of Bladder Cancer.

Bladder cancer (BC) is a prevalent disease with high morbidity and mortality; however, in vivo optical imaging of BC remains challenging because of the lack of cancer-specific optical agents with high renal clearance. Herein, a macromolecular reporter (CyP1) was synthesized for real-time near-infrared fluorescence (NIRF) imaging and urinalysis of BC in living mice. Because of the high renal clearance (ca. 94 % of the injection dosage at 24 h post-injection) and its cancer biomarker (APN=aminopeptidase N) specificity, CyP1 can be efficiently transported to the bladder and specially turn on its NIRF signal to report the detection of BC in living mice. Moreover, CyP1 can be used for optical urinalysis, permitting the ex vivo tracking of tumor progression for therapeutic evaluation and easy translation of CyP2 as an in vitro diagnostic assay. This study not only provides new opportunities for non-invasive diagnosis of BC, but also reveals useful guidelines for the development of molecular reporters for the detection of bladder diseases.

Inhibition of quorum sensing in opportunistic pathogen, Serratia marcescens, using cyclodextrin-immobilized, multiple parallel gel filaments fabricated with dynamic flow of polymer blend solution.

Prodigiosin production in the model opportunistic human pathogen, Serratia marcescens AS-1, depends on quorum sensing (QS), the activation of which is induced by an increase in N-hexanoyl homoserine lactone (C6HSL) concentration. When mixed with C6HSL in the broth culture of S. marcescens immobilized cyclodextrin (CD) effectively formed an inclusion complex resulting in suppression of the QS-mediated prodigiosin production. Thousands of parallel gel filament bundles could be fabricated by the dynamic flow of aqueous sodium alginate blended with α-CD or hydroxypropyl-ß-CD (HP-ß-CD) immobilized hydroxypropyl cellulose (HPC) inside a co-axial microfluidic device. Shear-induced fibrous domains of HPC-alginate complex assembly were immediately jacketed by calcium alginate gel formed by a sheath flow containing Ca2+ ions. Immobilized α-CD and HP-ß-CD on the HPC/alginate gel fibers could inhibit the C6HSL-mediated prodigiosin production to approximately 10%. Furthermore, the swarming motility of S. marcescens AS-1 was effectively suppressed in the presence of free or immobilized α-CD or HP-ß-CD. The CD-immobilized gel filament bundle is a novel type of preventive material against bacterial infections.

Polydopamine-coated polyethylene sieve plate as an efficient and convenient adsorption sink for the bioaccessibility prediction of PAHs in soils.

Bioaccessibility measurements of polycyclic aromatic hydrocarbons (PAHs) in soils are significant for exposure risk assessment. The current physicochemical methods require tedious operation processes, underestimate the actual risks, or are unsuitable for high organic content soils. In this work, an efficient and convenient method based on polydopamine-coated polyethylene sieve plate (PDA@PESP) and hydroxypropyl-ß-cyclodextrin (HPCD) was developed to predict the bioaccessibility of PAHs in multi-type soils. The PDA@PESP can be prepared via in situ self-polymerization, allowing to extract PAHs from HPCD solution quantitatively and rapidly. When applied to evaluate the bioaccessibility with PDA@PESP as an adsorption sink and HPCD as a diffusive carrier, the proposed method can significantly improve the extractable fraction of PAHs compared to single HPCD extraction in particular for high organic carbon content soil and high-ring PAHs. The desorption kinetics data indicated that the method can predict the bioaccessible fraction of PAHs. In addition, the method predicted a satisfactory accumulation into earthworms (Eisenia fetida) with a slope statistically approximated to 1. A highly significant linear regression (R2 = 0.95) was also found between the proposed method and Tenax desorption in historically contaminated soils, demonstrating that the method is an efficient and convenient approach for the bioaccessibility prediction of PAHs in soils.

Effect of hydroxypropyl-ß-cyclodextrin on the cometabolism of phenol and phenanthrene by a novel Chryseobacterium sp.

Cometabolic degradation is an effective method to remove the polycyclic aromatic hydrocarbons (PAHs) with phenol as growth substrate from coal chemical wastewater (CCW). Unfortunately, the toxicity and low solubility of PAHs always restrict their degradation. In this study, Chryseobacterium sp. H202 was firstly isolated from the aerobic segment of CCW. Then, to improve the cometabolic degradation of PAHs, the effects of hydroxypropyl-ß-cyclodextrin (HPCD) were investigated. Phenanthrene removal was accelerated in the presence of phenol; however, the degradation of phenol was inhibited because of the toxicity of phenanthrene. Addition of 50 mg/L HPCD accelerated the degradation of phenol and effectively improved the phenanthrene removal rate by about 55%. Inclusion of HPCD appeared to increase the apparent solubility and reduce the toxicity of phenanthrene, thereby improving the cometabolic degradation of phenol and phenanthrene. Therefore, HPCD can enhance the degradation of phenanthrene with phenol as the growth substrate during CCW treatment.

Lipase-catalyzed hydrolysis of (R,S)-2,3-diphenylpropionic methyl ester enhanced by hydroxypropyl-ß-cyclodextrin.

The enantioselective hydrolysis of (R,S)-2,3-diphenylpropionic methyl ester ((R,S)-2,3-2-PPAME) catalyzed by lipase to (R)-2,3-diphenylpropionic acid ((R)-2,3-2-PPA) was studied in an aqueous system. The catalytic effects of different types of lipase were compared, and Candida antarctica lipase A (CALA) with higher catalytic activity and enantioselectivity was selected. Hydroxypropyl-ß-cyclodextrin (HP-ß-CD) was added to the aqueous system to increase the solubility of 2,3-2-PPAME, which resulted in an increase of 35.56% in substrate conversion remaining the high enantiomeric excess. The factors influencing the substrate conversion and the optical purity of product such as temperature, pH, concentrations of CALA and HP-ß-CD, substrate loading, and reaction time were optimized. The optimal conditions for this reaction were obtained, including pH of 5.5, 30 mg/mL CALA, 25 mmol/L HP-ß-CD, 0.12 mmol substrate, temperature at 60 °C, agitation speed at 400 rpm, and 48 h for reaction time. Under these optimal conditions, the substrate conversion was up to 44.70% and the optical purity of the product (R)-2,3-2-PPA was up to 98.20%. This work provides an efficient alternative method for lipase-catalyzed enantioselective hydrolysis of 2,3-2-PPAME to (R)-2,3-2-PPA by ß-cyclodextrin inclusion in an aqueous reaction system of hydrolysis. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:1355-1362, 2018.

Hydroxypropyl-ß-Cyclodextrin and ß-Cyclodextrin as Tablet Fillers for Direct Compression.

Cyclodextrins are cyclic carbohydrates widely used as complexing and non-complexing excipients in drug delivery systems. The purpose of this work was to study the ability of hydroxypropyl-ß-cyclodextrin and ß-cyclodextrin to act as tablet fillers for direct compression. In this way, several parameters of the cyclodextrins were evaluated, namely: (i) the flow properties such as angle of repose, flow time, Carr index, and Hausner ratio; (ii) the compaction behavior, specifically the energies and forces exerted during tableting, the plasticity index, the lubrication efficiency, and compression profiles (force/time and work/displacement of the upper punch); and (iii) the influence on carbamazepine release characteristics from uncoated tablets, i.e., dissolution rate and disintegration time. In addition, these properties of the cyclodextrins were compared with those from other commonly used direct compression fillers (lactose monohydrate, mannitol, calcium hydrogen phosphate dihydrate, and microcrystalline cellulose) and co-processed excipients (microcrystalline cellulose/mannitol and lactose monohydrate/cellulose). Three main conclusions can be drawn: (i) the studied cyclodextrins can be used as tablet fillers for direct compression; (ii) hydroxypropyl-ß-cyclodextrin showed better properties than ß-cyclodextrin mainly at the level of the physics of compression (higher values of plasticity index and lubrication efficiency) and of the drug release characteristics (faster and greater dissolution rate and a shorter disintegration time); and (iii) lactose monohydrate and hydroxypropyl-ß-cyclodextrin displayed the best results. As there are people intolerant to lactose, hydroxypropyl-ß-cyclodextrin, although its cost is higher, can be considered a good substitute for lactose.