Hydroxypropyl Β-cyclodextrin Research Articles

Innovative Microencapsulation of Polymyxin B for Enhanced Antimicrobial Efficacy via Coated Spray Drying.

This study aims to develop an innovative microencapsulation method for coated Polymyxin B, utilizing various polysaccharides such as hydroxypropyl β-cyclodextrin, alginate, and chitosan, implemented through a three-fluid nozzle (3FN) spray drying process. High-performance liquid chromatography (HPLC) analysis revealed that formulations with a high ratio of sugar cage, hydroxypropyl β-cyclodextrin (HPβCD), and sodium alginate (coded as ALGHCDHPLPM) resulted in a notable 16-fold increase in Polymyxin B recovery compared to chitosan microparticles. Morphological assessments using fluorescence labeling confirmed successful microparticle formation with core/shell structures. Alginate-based formulations exhibited distinct layers, while chitosan formulations showed uniform fluorescence throughout the microparticles. Focused beam reflectance and histograms from fluorescence microscopic measurements provided insights into physical size analysis, indicating consistent sizes of 6.8 ± 1.2 μm. Fourier-transform infrared (FTIR) spectra unveiled hydrogen bonding between Polymyxin B and other components within the microparticle structures. The drug release study showed sodium alginate's sustained release capability, reaching 26 ± 3% compared to 94 ± 3% from the free solution at the 24 h time point. Furthermore, the antimicrobial properties of the prepared microparticles against two Gram-negative bacteria, Escherichia coli and Pseudomonas aeruginosa, were investigated. The influence of various key excipients on the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values was evaluated. Results demonstrated effective bactericidal effects of ALGHCDHPLPM against both E. coli and P. aeruginosa. Additionally, the antibiofilm assay highlighted the potential efficacy of ALGHCDHPLPM against the biofilm viability of E. coli and P. aeruginosa, with concentrations ranging from 3.9 to 500 μg/m. This signifies a significant advancement in antimicrobial drug delivery systems, promising improved precision and efficacy in combating bacterial infections.

Improving the bactericidal activity of carvacrol against Bacillus cereus by the formation of sodium casein-stabilized nanoemulsion and its application in milk preservation

Carvacrol has great antibacterial activity against Bacillus cereus, and its action mechanism was comprehensively studied in this work. It could not only control the growth of B. cereus by affecting the integrality of cellular structure and physiological metabolism, but also inhibit the swarming motility, biofilm formation, and toxins production. To increase the stability of carvacrol during the application, the sodium casein (SC)/hydroxypropyl-β-cyclodextrin (HPCD)/carvacrol nanoemulsion was fabricated. The mean particle size and polydispersity index of the nanoemulsions were 113.8 nm and 0.23, respectively, at SC and HPCD concentrations of 2% and 1%. FTIR analysis demonstrated that carvacrol was successfully encapsulated into the nanoemulsions. The MIC and MBC of nanoemulsions against B. cereus were 0.15 and 0.30 mg/mL, respectively, which were lower than those of free carvacrol (0.19 and 0.38 mg/mL). Carvacrol in nanoemulsions showed a slow and sustained release behavior. Furthermore, the nanoemulsions had good stability (particle size <200 nm) after storage at 4 °C and 25 °C for 15 days. Notably, the nanoemulsions were effective in controlling the growth of B. cereus in whole, low-fat, and skim milk and had better antimicrobial activity than free carvacrol. The results indicated that carvacrol nanoemulsions have potential in the antibacterial application of the food industry.

Solubility enhancement of etoricoxib using inclusion complexation with cyclodextrins: formulation of oro dispersible tablets by QbD approach

Background: The work was intended to enhance etoricoxib's solubility and dissolution rate and then develop oro-dispersible tablets for faster onset of action. Methodology: Inclusion complexes (ICs) of the drug were obtained with β-cyclodextrin (β-CD) and hydroxypropyl β-cyclodextrin (HP β-CD) at ratios of 1:0.125, 1:0.25, 1:0.5, 1:1, and 1:2 (w/w). The selected cyclodextrin at appropriate drug carrier proportion was used to develop oro-dispersible tablets (ODTs) by direct compression, adding crospovidone as a super disintegrant. Phase solubility studies of etoricoxib were carried out by using multiple concentrations of β-cyclodextrin and hydroxypropyl β-cyclodextrin, i.e., 1 %, 2 %, 3 % w/v in distilled water at 37±2°C. Spectroscopic (FT-IR) and thermal analysis (DSC) techniques were employed to identify the drug-carrier interactions. Result: It showed that etoricoxib solubility improves with increasing hydrophilic carrier concentration. The Gibbs free energy values (ΔG˚tr) are consistently negative, showing the solubility of etoricoxib. Significant drug carrier interaction in spectroscopic or thermal analysis was not found. Discussion: The ICs of drugs with β-CD and HP β-CD have successfully addressed the challenges of solubility enhancement and taste masking for etoricoxib. Conclusions: It is observed that the inclusion complexes formed by the kneading method using β-cyclodextrin (β-CD) at a 1:1 ratio and hydroxypropyl β-cyclodextrin (HP β-CD) at a 1:2 ratio can be used to improve dissolution. Hence β-CD (at a 1:1 ratio) is selected for the formulation of oro-dispersible tablets. ODTs offer more patient compliance and an alternative to available conventional tablets.

Formulation, Development, Characterization and Solubility Enhancement of Amisulpride

Background: Amisulpride (AMP) is a drug that is poorly water-soluble and is typically characterized by high molecular weights, significant log P values, and low bioavailability. Poor water solubility of a drug is caused by strong intermolecular interaction and a drug's affinity for a lipid environment (lipophilicity). Objective: The current study aims to improve Amisulpride's (AMP) oral bioavailability and solubility by developing a complex with 2-hydroxypropyl β-cyclodextrin (HP-β-CDT). Method: This study describes solubility of AMP with β-CDT and HP-β-CDT. Prepared inclusion complex of AMP and HP-β-CDT by different techniques like physical mixture, kneading and lyophilization. Result: A notable improvement in AMP's solubility was obtained with an optimized inclusion complex. The result of FT-IR, DSC and XRD confirms the complex between AMP and HP-β-CDT. The physical mixture, kneading and lyophilization technique, the kneading method is most successful in producing an inclusion complex. Conclusion: The 1.3 ratio gives the best drug content and dissolution profile.

Chiral nematic composite coatings as a visual detection platform for formic acid with anti-water interference

Formic acid is an important industrial chemical but is toxic and corrosive. To benefit its qualified use and to avoid corrosion or injury from touching, rapid, portable and sensitive on-site sensing of formic acid is thus of considerable importance. Here, a photonic crystal coating sensor for formic acid visual detection is fabricated through the mild co-assembly of both biomass-based cellulose nanocrystals (CNCs) and hydroxypropyl-β-cyclodextrin (HPCD) on a quartz glass slide. Further surface modification by hexadecyltrimethoxysilane (HTDMS) with low surface energy significantly overcomes the inherent water intolerance of the CNC-HPCD composite while maintaining its chiral nematic structure. The resulting hydrophobic CNC-HPCD (H-CNC) sensing slide shows a distinct and rapid structural color change after formic acid stimulation, realizing the formic acid detection by naked eye. By virtue of its stable and repeatable water resistance, the H-CNC sensing slide enables the specific colorimetric detection of formic acid in water-containing environments for qualitative and even quantitative purposes. This study suggests that H-CNC has the potential to act as a high-performance sensing platform that is useful for the colorimetric detection of formic acid in some industrial products.

7-Phenylheptanoic Acid-Hydroxypropyl β-Cyclodextrin Complex Slows the Progression of Renal Failure in Adenine-Induced Chronic Kidney Disease Mice.

The characteristic accumulation of circulating uremic toxins, such as indoxyl sulfate (IS), in chronic kidney disease (CKD) further exacerbates the disease progression. The gut microbiota, particularly gut bacterial-specific enzymes, represents a selective and attractive target for suppressing uremic toxin production and slowing the progression of renal failure. This study investigates the role of 4-phenylbutyrate (PB) and structurally related compounds, which are speculated to possess renoprotective properties in suppressing IS production and slowing or reversing renal failure in CKD. In vitro enzyme kinetic studies showed that 7-phenylheptanoic acid (PH), a PB homologue, suppresses the tryptophan indole lyase (TIL)-catalyzed decomposition of tryptophan to indole, the precursor of IS. A hydroxypropyl β-cyclodextrin (HPβCD) inclusion complex formulation of PH was prepared to enhance its biopharmaceutical properties and to facilitate in vivo evaluation. Prophylactic oral administration of the PH-HPβCD complex formulation reduced circulating IS and attenuated the deterioration of renal function and tubulointerstitial fibrosis in adenine-induced CKD mice. Additionally, treatment of moderately advanced adenine-induced CKD mice with the formulation ameliorated renal failure, although tissue fibrosis was not improved. These findings suggest that PH-HPβCD can slow the progression of renal failure and may have implications for preventing or managing CKD, particularly in early-stage disease.

Formation of Inclusion Complexes of 2-Hydroxypropyl β-Cyclodextrin with 2-Hydroxychalcone: Experimental and Theoretical Study

The formation of inclusion complexes of 2-hydroxypropyl-β-cyclodextrin (HP β-CD) with 2-hydroxychalcone (2HOCH) in solution and solid state was investigated using UV–Visible, fluorescence, Fourier transform-infrared (FT-IR) spectroscopy, powder X-ray diffraction (PXRD), scanning electron microscope (SEM) techniques. The results obtained confirmed that 2HOCH formed the stable inclusion complex with HP β-CD. Moreover, the spectral data and Benesi–Hildebrand plots results indicated that the stoichiometry of the inclusion complex was 1:1. Theoretically, the structure of the inclusion complexes and the physical parameters such as complexation energy, highest occupied molecular orbital–lowest unoccupied molecular orbital, and energy gap were obtained using the DFT/B3LYP/6-311G method. It was found that the complexation energy for orientation B was lower than that for orientation A as evidenced by the theoretical calculations. Moreover, the carbonyl group of molecules was located outside of the cyclodextrin cavity while the hydroxyl group was located inside the cavity. The antioxidant capacity and antibacterial responses of the inclusion complexes and, for comparison, the parent compounds were also carried out.

Evaluation of Solubility, Dissolution Rate, and Oral Bioavailability of β-Cyclodextrin and Hydroxypropyl β-Cyclodextrin as Inclusion Complexes of the Tyrosine Kinase Inhibitor, Alectinib.

This study aims to improve the solubility and dissolution rate of alectinib (ALB), a tyrosine kinase inhibitor commonly used for treating non-small-cell carcinoma (NSCLC). Given ALB's low solubility and bioavailability, complexation with β-cyclodextrin (βCD) and hydroxy propyl β-cyclodextrin (HPβCD) was evaluated. Some of the different preparation methods used with varying ALB-to-CD ratios led to the formation of complexes that were characterized using Fourier-Transform Infrared (FTIR) techniques and Differential Scanning Calorimetry (DSC) to prove complex formation. The encapsulation efficiency was also determined. The simulations were carried out for ALB's interactions with βCD and HPβCD. This study identified the most soluble complex (ALB-HPβCD; 1:2 ratio) and evaluated its dissolution. The bioavailability of the ALB-HPβCD complex was evaluated in Wistar rats relative to free ALB. Pharmacokinetic profiles revealed increased Cmax (240 ± 26.95 ng/mL to 474 ± 50.07 ng/mL) and AUC0-48 (5946.75 ± 265 ng.h/mL to 10520 ± 310 ng.h/mL) with no change in the elimination rate constant. In conclusion, the complexation of ALB-HPβCD manages to increase in vitro solubility, the dissolution rate, and oral bioavailability, providing a favorable approach to improving ALB administration.

A novel bioaccessibility prediction method for complex petroleum hydrocarbon mixtures in soil.

More evidence shows that bioaccessibility instead of total concentrations based on exhaustive extraction methods can better reflect the actual risk level of petroleum hydrocarbon contaminated sites, so it is essential to establish an effective assessment method for bioaccessibility. This study utilized Tenax extraction, butanol extraction, hydroxypropyl-β-cyclodextrin (HPCD) extraction, and a composite extraction method involving HPCD with LMWOAs (citric acid, CA) and surfactants (rhamnolipid, RL; Tween80, TW80; sodium dodecyl sulfate, SDS) at varying concentrations. These methods were employed to predict the bioaccessibility of earthworms to soil at different aging time of petroleum hydrocarbons. The results showed that traditional extraction methods such as Tenax 6h extraction and n-butanol extraction were ineffective in evaluating petroleum hydrocarbons' bioaccessibility. In contrast, the composite extraction of HPCD and solubilizer enhanced the extraction efficiency of HPCD greatly, and the extraction results showed a significant positive correlation with earthworm accumulation. By the comparison of the extraction results of different fractions of petroleum hydrocarbons, heavy fractions of petroleum hydrocarbons (C29-C40) are essential factors affecting chemical extraction effects. The correlation coefficients of four composite extraction methods and total petroleum hydrocarbons (TPH) of earthworm accumulation by linear regression analysis ranged from 1.1797 to 1.7990, and the slopes ranged from 0.8727 to 0.9792. Among them, the combined extraction method of 50 mmol/L HPCD and 0.5 mmol/L rhamnolipid had the best effect (r2 = 0.9792, slope = 1.1797), which could be used as an evaluation method suitable for the bioaccessibility of petroleum hydrocarbons in soil. This study could provide a new method for evaluating the bioaccessibility of organic pollutants and technically supporting risk assessment and bioremediation of complex petroleum hydrocarbons in soil.

Design and development of a chitosan-based nasal powder of dimethyl fumarate-cyclodextrin binary systems aimed at nose-to-brain administration. A stability study

The nasal administration route has been studied for the delivery of active molecules directed to the Central Nervous System, thanks to the anatomical connection between the nasal cavity and the brain.Dimethyl fumarate is used to treat relapsing-remitting multiple sclerosis, with a role as an immunomodulator towards T- T-cells and a cytoprotector towards neurons and glial cells. Its use in therapy is hindered by its low aqueous solubility, and low stability, due to hydrolysis and sublimation at room temperature. To overcome this limitation, in this study we evaluated the feasibility of using two amorphous β-cyclodextrin derivatives, namely hydroxypropyl β-cyclodextrin and methyl β-cyclodextrin, to obtain a nasally administrable powder with a view to nose-to-brain administration.Initially, the interaction product was studied using different analytical methods (differential scanning calorimetry, Fourier transform infrared spectroscopy and powder X-ray diffraction) to detect the occurrence of binary product formation, while phase solubility analysis was used to probe the complexation in solution.The dimethyl fumarate-cyclodextrin binary product showing best solubility and stability properties was subsequently used in the development of a chitosan-based mucoadhesive nasally administrable powder comparing different preparative methods. The best performance in terms of both hydrolytic stability and DMF recovery was achieved by the powder obtained via freeze-drying.

Supramolecular deep eutectic solvent: a powerful tool for pre-concentration of trace metals in edible oil.

The utilization of supramolecular deep eutectic solvent eddy-assisted liquid-liquid microextraction utilizing 2-hydroxypropyl β-cyclodextrin (SUPRADES) has been identified as a successful method for pre-enriching Cu, Zn, and Mn in vegetable oil samples. Determination of each element was conducted by inductively coupled plasma optical emission spectrometry (ICP-OES) after digestion of metal-enriched phases. Various parameters were examined, including the composition of SUPRADES species [2HP-β-CD: DL-lactic acid], a cyclodextrin mass ratio of 20wt%, a water bath temperature of 75 °C, an extractor volume of 800 μL, a dispersant volume of 50μL, and an eddy current time of 5min. Optimal conditions resulted in extraction rates of 99.6% for Cu, 105.2% for Zn, and 101.5% for Mn. The method exhibits a broad linear range spanning from 10 to 20,000μg L-1, with determination coefficients exceeding 0.99 for all analytes. Enrichment coefficients of 24, 21, and 35 were observed. Limits of detection ranged from 0.89 to 1.30μg L-1, while limits of quantification ranged from 3.23 to 4.29 μg L-1. The unique structural characteristics of the method enablethe successful determination of trace elements in a variety of edible vegetable oils.

Pharmaceutical Compounding in Veterinary Medicine: Suspension of Itraconazole.

Itraconazole is a drug used in veterinary medicine for the treatment of different varieties of dermatophytosis at doses between 3-5 mg/kg/day in cats. Nevertheless, in Spain, it is only available in the market as a 52 mL suspension at 10 mg/mL. The lack of alternative formulations, which provide sufficient formulation to cover the treatment of large animals or allow the treatment of a group of them, can be overcome with compounding. For this purpose, it has to be considered that itraconazole is a weak base, class II compound, according to the Biopharmaceutics Classification System, that can precipitate when reaching the duodenum. The aim of this work is to develop alternative oral formulations of itraconazole for the treatment of dermatophytosis. Several oral compounds of itraconazole were prepared and compared, in terms of dissolution rate, permeability, and stability, in order to provide alternatives to the medicine commercialized. The most promising formulation contained hydroxypropyl methylcellulose and β-cyclodextrin. This combination of excipients was capable of dissolving the same concentration as the reference product and delaying the precipitation of itraconazole upon leaving the stomach. Moreover, the intestinal permeability of itraconazole was increased more than two-fold.

Solving the puzzle of 2-hydroxypropyl β-cyclodextrin: Detailed assignment of the substituent distribution by NMR spectroscopy

2-Hydroxypropyl-β-cyclodextrin (HPBCD) is one of the most important cyclodextrin derivatives, finding extensive applications in the pharmaceutical sector. Beyond its role as an excipient, HPBCD achieved orphan drug status in 2015 for Niemann-Pick type C disease treatment, prompting research into its therapeutic potential for various disorders. However, the acceptance of HPBCD as an active pharmaceutical ingredient may be impeded by its complex nature. Indeed, HPBCD is not a single entity with a well-defined structure, instead, it is a complex mixture of isomers varying in substituent positions and the degree of hydroxypropylation, posing several challenges for unambiguous characterization. Pharmacopoeias' methods only address the average hydroxypropylation extent, lacking a rapid approach to characterize the substituent positions on the CD scaffold. Recognizing that the distribution of substituents significantly influences the complexation ability and overall activity of the derivative, primarily by altering cavity dimensions, we present a straightforward and non-destructive method based on liquid state NMR spectroscopy to analyze the positions of the hydroxypropyl sidechains. This method relies on a single set of routine experiments to establish quantitative assignment and it provides a simple yet effective tool to disclose the substitution pattern of this complex material, utilizing easily accessible (400 MHz NMR) instrumentation.

Combining BNCT with carbonic anhydrase inhibition for mesothelioma treatment: Synthesis, in vitro, in vivo studies of ureidosulfamido carboranes

Mesothelioma is a malignant neoplasm of mesothelial cells caused by exposure to asbestos. The average survival time after diagnosis is usually nine/twelve months. A multi-therapeutic approach is therefore required to treat and prevent recurrence. Boronated derivatives containing a carborane cage, a sulfamido group and an ureido functionality (CA-USF) have been designed, synthesised and tested, in order to couple Boron Neutron Capture Therapy (BNCT) and the inhibition of Carbonic Anhydrases (CAs), which are overexpressed in many tumours. In vitro studies showed greater inhibition than the reference drug acetazolamide (AZ). To increase solubility in aqueous media, CA-USFs were used as inclusion complexes of hydroxypropyl β-cyclodextrin (HP-β-CD) in all the inhibition and cell experiments. BNCT experiments carried out on AB22 (murine mesothelioma) cell lines showed a marked inhibition of cell proliferation by CA-USFs, and in one case a complete inhibition of proliferation twenty days after neutron irradiation. Finally, in vivo neutron irradiation experiments on a mouse model of mesothelioma demonstrated the efficiency of combining CA IX inhibition and BNCT treatment. Indeed, a greater reduction in tumour mass was observed in treated mice compared to untreated mice, with a significant higher effect when combined with BNCT. For in vivo experiments CA-USFs were administered as inclusion complexes of higher molecular weight β-CD polymers thus increasing the selective extravasation into tumour tissue and reducing clearance. In this way, boron uptake was maximised and CA-USFs demonstrated to be in vivo well tolerated at a therapeutic dose. The therapeutic strategy herein described could be expanded to other cancers with increased CA IX activity, such as melanoma, glioma, and breast cancer.

Inhibition of 7-dehydrocholesterol reductase prevents hepatic ferroptosis under an active state of sterol synthesis

Recent evidence indicates ferroptosis is implicated in the pathophysiology of various liver diseases; however, the organ-specific regulation mechanism is poorly understood. Here, we demonstrate 7-dehydrocholesterol reductase (DHCR7), the terminal enzyme of cholesterol biosynthesis, as a regulator of ferroptosis in hepatocytes. Genetic and pharmacological inhibition (with AY9944) of DHCR7 suppress ferroptosis in human hepatocellular carcinoma Huh-7 cells. DHCR7 inhibition increases its substrate, 7-dehydrocholesterol (7-DHC). Furthermore, exogenous 7-DHC supplementation using hydroxypropyl β-cyclodextrin suppresses ferroptosis. A 7-DHC-derived oxysterol metabolite, 3β,5α-dihydroxycholest-7-en-6-one (DHCEO), is increased by the ferroptosis-inducer RSL-3 in DHCR7-deficient cells, suggesting that the ferroptosis-suppressive effect of DHCR7 inhibition is associated with the oxidation of 7-DHC. Electron spin resonance analysis reveals that 7-DHC functions as a radical trapping agent, thus protecting cells from ferroptosis. We further show that AY9944 inhibits hepatic ischemia-reperfusion injury, and genetic ablation of Dhcr7 prevents acetaminophen-induced acute liver failure in mice. These findings provide new insights into the regulatory mechanism of liver ferroptosis and suggest a potential therapeutic option for ferroptosis-related liver diseases.

Pluronic-coated hydroxypropyl-β-cyclodextrin nanoparticle potentiated chemotherapy on multidrug resistance cancer cells via improved docetaxel loading and P-glycoprotein inhibition

In the pharmaceutical formulation of anticancer drugs, US FDA-approved cyclodextrin (CD) and its derivates have been widely employed. Among them, hydroxypropyl β-cyclodextrin (HPCD) has attracted considerable attention owing to low toxicity, improved water solubility, and enhanced drug absorption; however, HPCD exhibits low drug loading efficiency and poor anticancer efficacy in multidrug-resistant (MDR) cancer cells. Therefore, to improve the drug loading efficiency and simultaneously overcome the MDR effects, we developed docetaxel (DTX)-loaded Pluronic®(PLU)-coated hydroxypropyl-β-cyclodextrin nanoparticles (DTX@PLU/HPCD NPs). We employed a simple nanoprecipitation technique, wherein PLU acted as a P-glycoprotein inhibitor to overcome MDR and an enhancer to achieve high drug loading. The HPCD NPs were coated with PLU (PF127, PP123, and PL81) of varying hydrophilic/lipophilic balance values, and the amount of encapsulated DTX was optimized. The DTX-loaded HPCD formulations (DTX@HPCD NP, DTX@PF127/HPCD NP, and DTX@PP123/HPCD NP) exhibited good stability and facilitated sustained release. The HPCD formulations exerted no cytotoxicity against examined cancer cell lines (HCT15 and SCC 7). DTX@PLU/HPCD NPs exerted potent anticancer effects in vitro. Notably, DTX@PP123/HPCD NPs significantly reduced the tumor volume in a mouse model. Collectively, these results indicate that PLU/HPCD NPs could function as drug carriers to alleviate toxicity and overcome MDR in various cancer models.

The characterization of the pectin/alginate nanoparticle for encapsulation of hydroxypropyl-β-cyclodextrin-complexed naringin and its effects on cellular uptake and oxidative stress in Caco-2 cells

Naringin (NR) and hydroxypropyl-β-cyclodextrin (HPCD) can form a water-soluble complex, but it is unstable. This study aimed to investigate the characterization of the pectin/alginate hydrogel nanoparticles (HNPs) loading HPCD-complexed naringin. The encapsulation efficiency and loading capacity of the HNPs for NR were found to be 79.23 % ± 1.31 % and 23.79 % ± 0.67 %, respectively. HNPs had an average diameter of 409.5 ± 8.5 nm, a PDI of 0.237 ± 0.014, and a zeta-potential of −33.5 ± 0.2. FTIR, XRD, and DSC analysis confirmed that the NR-HPCD complex was embedded into the HNPs. In simulated gastrointestinal digestion, the HNPs exhibited a lower cumulative release rate compared to free NR. In Caco-2 cells, the HNPs were more efficiently transported into the cells. Consequently, the HNPs resulted in a greater decrease in ROS levels, more recovery of mitochondrial membrane potential and higher content of glutathione. This study provided a carrier for encapsulating NR, making it possible for use in food or functional food.

Dispersive solid phase extraction based on cross-linked hydroxypropyl β-cyclodextrin polymers for simultaneous enantiomeric determination of three chiral triazole fungicides in water.

Anefficient method is presentedfor simultaneous enantioselective determination of three chiral triazole fungicides (namely paclobutrazol, hexaconazole, and diniconazole) in water samples by DSPE-HPLC-UV. The perfect chiral separation of the enantiomers was achieved on a Chiralpak IH column within 15min. In order to adsorb and enrich the analytes from water matrices, a cross-linked hydroxypropyl β-cyclodextrin polymer was synthesized. The prepared material exhibited good adsorption capacity, which was assessed by adsorption kinetic and adsorption thermodynamic experiments. One-variable-at-a-time and the response surface methodology were used to optimize the extraction parameters. Under the optimum sample preparation conditions, good linearity (2.0 ~ 800µg L-1, R2 ≥ 0.9978), detection limits (0.6 to 1.0µg L-1), quantitation limits (2.0 to 3.2µg L-1), recoveries (86.7 ~ 105.8%), and the relative standard deviation (intra-day RSD ≤ 3.7%, inter-day RSD ≤ 5.1%) were obtained, satisfying the requirements of pesticides residues determination. These results demonstrated that the proposed method was applicable for routine determination of chiral triazole fungicide residues in water samples.

Inclusion complexes of bedaquiline fumarate with β-cyclodextrin and its derivatives: In silico, in vitro and in vivo evaluation

Bedaquiline fumarate (BQF), a BCS class-II drug, shows dissolution rate-dependent absorption pattern, which results in poor biopharmaceutical performance. In this research, we formulated β-cyclodextrin (β-CD) and hydroxypropyl β-cyclodextrin (HP-β-CD) inclusion complexes (ICs) of BQF to improve its biopharmaceutical attributes. ICs were prepared by freeze drying method and characterized using NMR, FTIR, DSC, PXRD and polarised microscopy. These complexes were evaluated for in vitro dissolution and optimized BQF-HP-β-CD ICs was further evaluated for cytotoxicity, intestinal permeability, and in vivo pharmacokinetic studies. 1D and 2D NMR and FTIR confirmed hydrogen bonding between BQF and cyclodextrins. DSC, PXRD and polarised microscopy confirmed the amorphous nature of BQF in complexes. In vitro dissolution study showed 29.6 and 57.5-fold enhancement in dissolution efficiency (DE60) for BQF-β-CD and BQF-HP-β-CD IC, respectively, in comparison to BQF. The selected BQF-HP-β-CD IC was found to be compatible to Caco-2 cells and a 5-fold enhancement in the intestinal permeability. In vivo pharmacokinetic studies demonstrated an increase in Cmax and relative bioavailability of BQF with BQF-HP-β-CD IC in comparison to BQF suspension.

Comparative Investigation into the Roles of Imipenem:Cyclodextrin Complexation and Antibiotic Combination in Combatting Antimicrobial Resistance in Gram-Negative Bacteria.

Extensively drug-resistant (XDR), multidrug-resistant (MDR) and pandrug-resistant (PDR) Gram-negative microorganisms (GNBs) are considered a significant global threat. β-lactam and aminoglycoside combinations and imipenem:cyclodextrin inclusion complexes were studied for the treatment of lethal GNBs. This is because of the broad empiric coverage of the two drugs and their possession of different spectra of activity. Two cyclodextrins (β- and hydroxy propyl β-cyclodextrins) were utilized for inclusion complex formation with imipenem using the physical and kneading methods. In silico investigation using the molecular docking and Fourier-infrared spectroscopy (FTIR) were employed to estimate binding constant and confirm complex formation, respectively. The in vitro effects of amikacin and imipenem combination in comparison to the effect of imipenem-β- and hydroxy propyl β-cyclodextrin (CD) complexes against Klebsiella spp. and Acinetobacter baumannii were studied. The isolated microorganisms' antimicrobial responsiveness to various antibiotics (19 antibiotics) was evaluated. It was found that piperacillin/tazobactam and gentamycin (resistance rates were 33.3% and 34%, respectively) were the most effective antimicrobials. The in vitro studies have been performed by the checkerboard technique and time-killing assay. The studied combination of amikacin and imipenem showed a substantial drop in bacterial count (p < 0.05). The in vitro studies demonstrated a synergism for the investigated combination. Conventional PCR was used in molecular studies to identify the resistance genes bla IMP and aac (6')-Ib. The blaIMP and aac (6')-Ib were recorded in 38.2% and 3.6% of the studied isolates, respectively. The in vitro studies showed synergistic effects among the tested antibiotics with FICIs of ≤0.5. Finally, the study compared the reduction in bacterial count between the tested antibiotic combinations and imipenem:CD physical and kneaded mixtures. Imipenem:CD inclusion complexes demonstrated a significant bacterial count reduction over the antibiotic combination. These results highlight the emerging role of CDs as safe biofunctional excipients in the combat against superbug bacterial resistance.