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The aim of the study was to produce dual nanofibers (NFs) with antibacterial and antioxidant properties, and to determine the potential use of dual NFs in food preservation. For this purpose, Polycaprolactone (PCL) polymers and Hydroxypropyl Beta Cyclodextrin (HPβ‐CD) polymer were used to produce nanofibers. Nisin, which is in the GRAS class, was used for the antibacterial properties of NFs and black seed cumin oil (BCSO) was used for antibacterial and antioxidant effects. PCL_BCSO‐NFs has an antimicrobial effect on both Gram‐positive and Gram‐negative bacteria. Furthermore, PCL_BCSO‐NFs showed antibacterial activity of 50 % and above after long periods of storage at the room temperature. Nisin loaded HPβ‐CD‐NF and dual layer nanofiber exhibited antibacterial activity of 3.5±0.3 cm and 3.1±0.3 cm zone diameter against S. aureus and E. coli respectively. Furthermore, PCL/BCSO‐HPβ_CD/Nisin‐NFs showed a high antimicrobial effect until day 60. Antioxidant activity of PCL_BCSO‐NFs was 63.2 % while 52.9 % was observed by dual layer NFs. In addition, the antioxidant activity of PCL/BCSO‐HPβ_CD/Nisin‐NFs ranged from 52 to 70 % for 1d and 7 days storage period. Therefore, nanofiber based mats containing BCSO and nisin as a food packaging material can potentially provide protection to extend the shelf life of food products. [ABSTRACT FROM AUTHOR]

BackgroundNiemann-Pick Disease Type C (NPC) is an inherited, often fatal neurovisceral lysosomal storage disease characterized by cholesterol accumulation in every cell with few known treatments. Defects in cholesterol transport cause sequestration of unesterified cholesterol within the endolysosomal system. The discovery that systemic administration of hydroxypropyl-beta cyclodextrin (HPβPD) to NPC mice could release trapped cholesterol from lysosomes, normalize cholesterol levels in the liver, and prolong life, led to expanded access use in NPC patients. HPβCD has been administered to NPC patients with approved INDs globally since 2009.ResultsHere we present safety, tolerability and efficacy data from 12 patients treated intravenously (IV) for over 7 years with HPβCD in the US and Brazil. Some patients subsequently received intrathecal (IT) treatment with HPβCD following on average 13 months of IV HPβCD. Several patients transitioned to an alternate HPβCD. Moderately affected NPC patients treated with HPβCD showed slowing of disease progression. Severely affected patients demonstrated periods of stability but eventually showed progression of disease. Neurologic and neurocognitive benefits were seen in most patients with IV alone, independent of the addition of IT administration. Physicians and caregivers reported improvements in quality of life for the patients on IV therapy. There were no safety issues, and the drug was well tolerated and easy to administer.ConclusionsThese expanded access data support the safety and potential benefit of systemic IV administration of HPβCD and provide a platform for two clinical trials to study the effect of intravenous administration of HPβCD in NPC patients.

Ibuprofen is a widely‐used non‐steroidal anti‐inflammatory drug, which belongs to class II of Biopharmaceutics classification system with low aqueous solubility and dissolution rate and bioavailability problems. This study was conducted to synthesis, optimization, and evaluation of the inclusion complex of ibuprofen‐hydroxypropyl‐beta‐cyclodextrin to overcome the challenges. Complex of ibuprofen and hydroxypropyl‐beta‐cyclodextrin (HPβCD) was prepared by co‐evaporation method in different ratios of solvents (methanol, ethanol, and distilled water were used as solvent systems). In order to find out the optimum solvent ratio, molecular dynamics simulations were performed by NAMD 2.9 software. Differential scanning calorimetry was applied to assess the complexes crystallinity and thermal behaviors. Also, Fourier transform infrared was used to monitor structural changes. Furthermore, the solubility and dissolution profiles of complexes were evaluated and compared. Complexation with HPβCD was able to reduce crystallinity and improve the thermal stability, water solubility, and dissolution profile of all synthesized complexes. HPβCD complexation using ethanol and water solvents in the ratio of 9 : 1 and 3 : 1, increased the aqueous solubility of ibuprofen by 1155 % and 874 %, respectively that was considered as the optimum approach. The results indicated that complexation with HPβCD may be of potential use for improving the ibuprofen dissolution rate and bioavailability. [ABSTRACT FROM AUTHOR]

[Display omitted] • There is a significant demand for drugs with easily soluble, and non-toxic for human use. • The changes in absorbance and fluorescence intensity, indicate a 1:1 ratio of LXP with Hyd-β-CD. • ROESY analyses show that the LXP is outside of the cavity of Hyd-β-CD. • Hydrogen bonding is involved in the orientations, providing the specific bonding patterns. • Cell viability indicates the increased solubility, and does not induce toxicity in normal cells. • The anti-inflammatory efficacy of LXP is markedly enhanced in its IC form. In recent days, there has been a significant demand for drugs that are easily soluble, non-toxic, safe, and biocompatible for human use. Recently, active pharmaceutical ingredient (API) complexes with cyclodextrins (CDs) and their derivatives have gained considerable attention. In line with this trend, we have developed an inclusion complex material for loxoprofen using hydroxypropyl derivatives of beta-cyclodextrin (Hyd-β-CD). The formation of the complex between loxoprofen (LXP) and Hyd-β-CD has been confirmed through changes in absorbance and fluorescence intensity, indicating a 1:1 stoichiometric ratio. The addition of Hyd-β-CD significantly enhanced the solubility of LXP, reflecting successful complexation. Proton NMR and ROESY analyses show that the phenyl group of LXP resides within the cavity of the Hyd-β-CD. Further validation is provided by DFT orientations and their associated energy parameters. Cell viability studies indicate that the increased solubility of the inclusion complex (IC) improves the bioavailability of the drug, while toxicity tests show that our IC material does not induce toxicity in normal cells. Moreover, the anti-inflammatory efficacy of LXP is markedly enhanced in its IC form. These findings underscore the potential of IC in extending the application of LXP, especially in pharmaceuticals, where the enhanced stability and efficacy of natural active ingredients and anti-inflammatory agents are crucial. [ABSTRACT FROM AUTHOR]

In this study, the enhanced solubilization performance of a poorly soluble drug, beclomethasone dipropionate (BDP), was investigated using hydroxypropyl-β-cyclodextrin (HP-β-CD) and ethanol. The enhanced solubility of the drug was determined using the phase solubility method and correlated as a function of both HP-β-CD and ethanol concentrations. The effective progress of drug solubility originated from the formation of cyclodextrin and BDP inclusion complexes and increase in the lipophilicity of the medium, by aqueous ethanol, for hydrophobic BDP. BDP and HP-β-CD composite particles were produced using supercritical assisted atomization (SAA) with carbon dioxide as the spraying medium, 54.2% (w/w) aqueous ethanol as the solvent, and an optimal amount of the dispersion enhancer leucine. The effect of the mass ratio of HP-β-CD to BDP (Z) on the in vitro aerosolization and in vitro dissolution performance of BDP–HP-β-CD composite particles was evaluated. The aerosolization performance showed that the fine particles fraction (FPF) of the composite particles increased with increasing mass ratio. The water-soluble excipient (HP-β-CD) effectively enhance the dissolution rate of BDP from composite particles. This study suggests that BDP–HP-β-CD composite particles produced using SAA can be employed in immediate-release drug formulations for pulmonary delivery. [ABSTRACT FROM AUTHOR]

Purpose: Difluprednate (DFP) is an approved corticosteroid, available as an ophthalmic emulsion (Durezol®), used to treat pain and inflammation of the eye following ocular surgeries. This study utilized hydroxypropyl-β-cyclodextrin (HPBCD)-based DFP ophthalmic solution for improved ocular delivery. Methods: The DFP-HPBCD complex formation was studied in the liquid and solid states. Phase solubility, molecular docking studies, differential scanning calorimetry, and Fourier transform infrared spectroscopy suggested inclusion complexation of DFP and HPBCD. Results: DFP-HPBCD-based eye drops (solution) provided 16 and 26 times higher transcorneal permeation when compared to the suspension (no HPBCD, control) and Durezol, respectively (P < 0.001). In addition, ocular drug distribution studies conducted in continuously perfused whole porcine eyes showed DFP permeated into all of the ocular tissues in significantly higher amounts than Durezol. Conclusions: The solution-based eye drops in this study is iso-osmotic, safe, and more permeable in porcine eyes compared to Durezol. [ABSTRACT FROM AUTHOR]

Abstract Background Niemann-Pick Disease Type C (NPC) is an inherited, often fatal neurovisceral lysosomal storage disease characterized by cholesterol accumulation in every cell with few known treatments. Defects in cholesterol transport cause sequestration of unesterified cholesterol within the endolysosomal system. The discovery that systemic administration of hydroxypropyl-beta cyclodextrin (HPβPD) to NPC mice could release trapped cholesterol from lysosomes, normalize cholesterol levels in the liver, and prolong life, led to expanded access use in NPC patients. HPβCD has been administered to NPC patients with approved INDs globally since 2009. Results Here we present safety, tolerability and efficacy data from 12 patients treated intravenously (IV) for over 7 years with HPβCD in the US and Brazil. Some patients subsequently received intrathecal (IT) treatment with HPβCD following on average 13 months of IV HPβCD. Several patients transitioned to an alternate HPβCD. Moderately affected NPC patients treated with HPβCD showed slowing of disease progression. Severely affected patients demonstrated periods of stability but eventually showed progression of disease. Neurologic and neurocognitive benefits were seen in most patients with IV alone, independent of the addition of IT administration. Physicians and caregivers reported improvements in quality of life for the patients on IV therapy. There were no safety issues, and the drug was well tolerated and easy to administer. Conclusions These expanded access data support the safety and potential benefit of systemic IV administration of HPβCD and provide a platform for two clinical trials to study the effect of intravenous administration of HPβCD in NPC patients.

[Display omitted] Prilling/vibration technique to produce oral microcapsules was explored to achieve local delivery of misoprostol (MIS), a prostaglandin E1 analogue indicated for the treatment of gastric-duodenal ulcers, at the gastric mucosa. To improve MIS chemical stability and reduce its associated systemic side effects, drug delivery systems were designed and developed as microcapsules consisting of a core of sunflower oil and MIS (F s6 and F s14) or a MIS complex with hydroxypropyl-beta-cyclodextrin (HP-β-CD) (F s18), confirmed by specific studies, and a polymeric shell. The produced microcapsules showed high encapsulation efficiencies for those with MIS solubilized in sunflower oil (>59.86 %) and for the microcapsules with MIS/HP-β-CD (97.61 %). To demonstrate the ability of these systems to deliver MIS into the stomach, swelling and drug release experiments were also conducted in simulated gastric fluid. Among the three formulations, F S18 showed gastric release within 30 min and was the most advantageous formulation because the presence of the MIS/HP-β-CD inclusion complex ensured a greater ability to stabilise MIS in the simulated gastric environment. In addition, these new systems have a small size (<540 µm), and good flow properties and the dose of the drug could be easily adapted using different amounts of microcapsules (flexibility), making them a passepartout for different age population groups. [ABSTRACT FROM AUTHOR]

Persian sturgeon (Acipenser persicus) is an endangered species and genetic resource banking such as gametes and embryo preservation could be one of the most pursued conservation approaches. In this study, deleterious effects of the traditional cryopreservation technique and the effect of different doses of 2-hydroxypropyl-beta-cyclodextrin (HβCD) on thawed spermatozoa quality (motility duration and percentage) of Persian sturgeon (Acipenser persicus) were investigated from metabolic aspects of view. For cryopreserving, semen was diluted with Tris–HCl (100 mM) extenders containing 0, 5, 10, and 15 mM of HβCD in a ratio of 1:1 (semen/extenders). Semen-extenders were filled into 0.5-mL straws and were frozen with the vapor of liquid nitrogen, and then immersed into liquid nitrogen. Cryopreserved spermatozoa were thawed in water baths in 15 s. Two treatments with the highest and the lowest motility percentages (0 and 10 mM of HβCD) were chosen to reveal the extremes of the metabolites change range and were objected to 1H NMR spectroscopy. Univariate (ANOVA) and multivariate (PCA) analysis of the obtained metabolic profiles showed significant changes (P < 0.05) in metabolites. The use of 10 mM of HβCD was completely successful in the preservation of creatinine, glucose, guanidoacetate, O-phosphocholine, and N, N-dimethylglycine and probably their corresponding biochemical pathways, but it failed to preserve lactate, carnitine, betain, β-alanin, and trimethylamine N-oxide. It was also partially successful in preserving acetate, creatine, creatine phosphate, and glycine, all suggesting how HβCD can be effective as a cryoprotectant. [ABSTRACT FROM AUTHOR]

Abstract A new renaissance started in the research and application of cyclodextrins a few years ago. 2-Hydroxypropyl-beta-cyclodextrin (HPBCD) is used in the formulation of drugs and recently orphan designation was granted for the treatment of Niemann-Pick disease, type C. HPBCD is considered to be safe, but the exact mechanism of action and side effects are not completely explained. Labeled cyclodextrin derivatives are required to reveal the biological activity and in vivo distribution by imaging techniques. The aims of our study were to synthetize the 68Ga-labeled NODAGA-hydroxypropyl-beta-cyclodextrin (68Ga-NODAGA-HPBCD) and test the pharmacokinetic properties and in vivo distribution of this radiolabeled molecule. p -NCS-benzyl-NODA-GA (NODAGA) was conjugated to the 6-deoxy-6-monoamino-(2-hydroxypropyl)-β-cyclodextrin (NH 2 -HPBCD). The product (NODAGA-HPBCD) was analyzed by analytical RP-HPLC and verified with high resolution mass spectrometry. In the next step the NODAGA-HPBCD was labeled with Gallium-68 (68Ga). The 68Ga labeled NODAGA-HPBCD (68Ga-NODAGA-HPBCD) was characterized and the radiochemical purity (RCP%), partition coefficient (log P values), and in vitro stability was determined. Thereafter in vivo distribution and pharmacokinetic properties of 68Ga-NODAGA-HPBCD was monitored by positron emission tomography (PET). NODAGA-HPBCD was purified by preparative RP-HPLC and the purity was better than 98%. The radiochemical purity of the 68Ga-NODAGA-HPBCD was higher than 98%, the specific activity was 17.62 ± 2.43 GBq/μmol, and the decay corrected yield was 76.54 ± 6.12% (n = 8). The octanol/water partition coefficient of 68Ga labeled NODAGA-HPBCD was found to be −3.07 ± 0.11. In vivo dynamic and ex vivo biodistribution studies using control BALB/c mice revealed that 68Ga labeled NODAGA-HPBCD was mainly excreted by the kidney, due to its hydrophilic properties that has been proved by the partition coefficient. The accumulation of the radiotracer in abdominal organs was low, and no uptake was found in the brain. In conclusion 68Ga labeled NODAGA-HPBCD was successfully produced for the first time and tested in vitro and in vivo. The synthesized NODAGA-HPBCD was characterized and labeled with 68Ga successfully. Overall, the outcome of our study indicates that the in vivo behavior of radiolabeled cyclodextrins can be examined by PET techniques, thus these derivatives are suitable for further pharmacokinetic measurements. Graphical abstract Unlabelled Image [ABSTRACT FROM AUTHOR]

Propolis is a natural resinous material with antimicrobial, anti-inflammatory, antioxidant, antibiotic and anti-carcinogenic properties. Propolis coprecipitation was attempted by Supercritical Assisted Atomization (SAA) using two carriers: hydroxypropyl-β-cyclodextrin (HPβCD) and polyvinylpyrrolidone (PVP), with the aim to protect propolis bioactivity against: oxidation and to improve its bioavailability. Propolis/carrier ratio and overall solute concentration were investigated to understand their effect on the success of coprecipitation as solid dispersion of propolis in the carrier matrix and on particle morphology and particle size distribution. The results confirmed the efficiency of SAA process: spherical amorphous particles were obtained in which propolis and carrier were coprecipitated, with a mean diameter ranging between about 0.20 and 0.37 µm for HPβCD coprecipitates and between about 0.23 and 0.50 µm for PVP coprecipitates. SAA particles showed a polyphenol loading efficiency up to 100% for HPβCD coprecipitates and up to 96% for PVP coprecipitates, with a half inhibition concentration of DPPH radical up to (17.2 ± 2.8) µg/mL and (17.3 ± 1.0) µg/mL, respectively. These particles rich in bioactive compounds can be used as functional component in formulations of new food or pharmaceutical products. [ABSTRACT FROM AUTHOR]

A new delivery system based on loading of drug into nanostructured lipid carriers (NLC) and then encapsulating it into hydroxypropyl-β-cyclodextrin (HPCD) has been developed for rutin (RT) to overcome its limitation for practical application. Light microscope, scanning electronic microscope (SEM) and differential scanning calorimeter (DSC) were used to determine the morphology, microstructure and thermal properties of rutin-loaded microencapsulated nanostructured lipid carriers (RT-loaded MNLC), respectively. The effect of HPCD on the performance of RT-loaded MNLC was investigated in terms of particle size, entrapment efficiency, UV absorptivity and in vitro release. It is revealed that the combined encapsulated technology could successfully resolve the leakage and instability problems of rutin. The obtained RT-loaded MNLC in the size range of 210-270 nm (polydispersity index < 0·4) were spherical and homogeneous. The presence of HPCD influences the particle size, entrapment efficiency and release profile of rutin and has synergistic effect on UV protection. [ABSTRACT FROM AUTHOR]

We have tested the efficacy of hydroxypropyl-beta-cyclodextrin (HPBCD) delivered by the nasal route in the mouse model of juvenile Niemann-Pick C1 disease (NPC1), as pulmonary disease has not responded to systemic therapy with this drug. Since mice have no gag reflex, coating of the nasal cavity, with possible access to the brain, would be followed by delivery of HPBCD to the lung. While foamy macrophages, containing stored cholesterol, were found in the Npc1nmf164 homozygous mice, a marked inflammatory response was found with inhaled HPBCD, both in mutant and wild-type animals. Slight inflammation also occasionally occurred with saline inhalation. There was no difference between the saline-treated, HPBCD-treated, and untreated Npc1nmf164 homozygous mice for weight, balance beam performance, or coat hanger performance. Interestingly, there was a trend to longer survival in the HPBCD-treated Npc1nmf164 homozygous mice, which, when combined with the survival times of the saline-treated survivals (each of which was not different), became significant. [ABSTRACT FROM AUTHOR]

In vitro drug release testing and ex vivo transcorneal drug permeation can provide valuable information on the performance of the Q1/Q2 equivalent ointments prior to any animal studies. Good correlation between in vitro and ex vivo drug release may be indicative of good in vitro and in vivo correlation. Accordingly, it is important to investigate in vitro as well as ex vivo drug release from Q1/Q2 equivalent ophthalmic ointments and evaluate whether a correlation between these release profiles can be established. Four Q1/Q2 equivalent loteprednol etabonate ointments were prepared using different processing methods and excipient sources. The rheological parameters (crossover modulus and K value) of the four formulations were determined. The in vitro drug release testing of the four ointment formulations were performed using three different apparati (Franz diffusion cells, USP apparatus 2 with enhancer cells and USP apparatus 4 with semisolid adapters). Three models (zero order, logarithmic and the Higuchi model) were used to study the release kinetics of the ointment formulations. The transcorneal (rabbit corneas) permeation studies were performed using spherical joint Franz diffusion cells. The USP apparatus 4 method demonstrated better discriminatory ability compared to the USP apparatus 2 and the Franz diffusion cell methods. The in vitro release profiles of the four Q1/Q2 equivalent ointments with manufacturing differences showed a better fit using the Higuchi model (R 2  > 0.98) for all three release testing methods, compared to the other two models. Ex vivo drug release through the rabbit corneas displayed zero order release kinetics. A logarithmic correlation between rheological parameters (crossover and K value) and transcorneal flux were established. In addition, a plot of the in vitro release rate against the ex vivo release flux of the four ointment formulations, yielded a straight line (R 2  > 0.98) for all three release methods. Accordingly, the rheological parameters may be useful in predicting in vitro as well as ex vivo release properties. [ABSTRACT FROM AUTHOR]

The Npc1 nmf164 allele of Npc1 provides a mouse model for Niemann-Pick disease type C1 (NPC1), a genetic disease known to have a widely variable phenotype. The transfer of the Npc1 nmf164 mutation from the C57BL/6J inbred strain to the BALB/cJ inbred strain increased the mean lifespan from 117.8 days to 153.1 days, confirming that the severity of the NPC1 phenotype is strongly influenced by genetic background. The transfer of another Npc1 allele, Npc1 nih , to this background also extended survival of the homozygotes indicating that the modifying effect of BALB/cJ is not limited to a single allele of Npc1 . The increased longevity due to the BALB/cJ background did not map to a previously mapped modifier on chromosome 19, indicating the presence of additional genes impacting disease severity. The previously studied Glial Fibrillary Acidic Protein promoter- Npc1 cDNA transgene (GFAP-Npc1) which only expresses NPC1 in astrocytes further extended the lifespan of Npc1 nmf164 homozygotes on a BALB/cJ background (up to 600 days). Hydroxypropyl-β-cyclodextrin (HPβCD) treatment, not previously tested in the Npc1 nmf164 mutant, extended life in the Npc1 nmf164 homozygotes but not the transgenic, Npc1 nmf164 mice on the BALB/cJ background. In all cases, lack of weight gain and early cerebellar symptoms of loss of motor control were found. At termination, the one mouse sacrificed for histological studies showed severe, diffuse pulmonary alveolar proteinosis suggesting that pulmonary abnormalities in NPC1 mouse models are not unique to the Npc1 nih allele. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) has become a globally rising issue that can cause liver-related morbidity and mortality. Recent studies have revealed that a high-fat diet (HFD) highly contributes to the prevalence and progression of NAFLD via impacting gut microbiota and lipid metabolism signal pathways. Resveratrol (RSV), a natural bioactive compound, has exhibited potential for preventing and alleviating NAFLD. However, due to the poor bioavailability of RSV, its strengths and underlying mechanisms for NAFLD therapeutic potential are poorly understood. To address this, we utilized Hydroxypropyl-beta-Cyclodextrin (HBC) to encapsulate RSV to enhance its water solubility and conducted prevention and intervention experiments in HFD-fed mice. The results showed that the HBC has significantly enhanced the water solubility of RSV by 250-fold and the HBC-RSV better prevented and alleviated the liver steatosis, obesity and abnormal lipid metabolism induced by HFD than RSV alone. Meanwhile, combining HFD and HBC-RSV or RSV prevented HFD mice progressing to NAFLD. Besides, further investigation indicated that RSV could resist liver injury and obesity by modulating gut microbiota, raising the levels of short-chain fatty acids (SCFAs) and activating AMP-activated protein kinase (AMPK) signaling pathway. The activated pathway down-regulated sterol receptor element binding protein 1c (SREBP1c) and acetyl-coenzyme A carboxylase (ACC) to decrease lipid synthesis and up-regulated peroxisome proliferators-activated receptorα (PPARα) to promote the fatty acid oxidation, thus preventing NAFLD. Our findings suggested that water solubility-enhanced RSV beneficially modulated gut microbiota, altered gut microbiota-derived SCFAs, and activated lipid metabolism regulatory pathways, providing potential for NAFLD prevention and alleviation. [ABSTRACT FROM AUTHOR]

2-Hydroxypropyl-beta-cyclodextrin (HPBCD) is utilized in the formulation of pharmaceutical products and recently orphan designation was granted for the treatment of Niemann−Pick disease, type C. The exact mechanism of HPBCD action and side effects are not completely explained. We used fluorescently labelled hydroxypropyl-beta-cyclodextrin (FITC-HPBCD) to study its pharmacokinetic parameters in mice and compare with native HPBCD data. We found that FITC-HPBCD has fast distribution and elimination, similar to HPBCD. Interestingly animals could be divided into two groups, where the pharmacokinetic parameters followed or did not follow the two-compartment, first-order kinetic model. Tissue distribution studies revealed, that a significant amount of FITC-HPBCD could be detected in kidneys after 60 min treatment, due to its renal excretion. Ex vivo fluorescent imaging showed that fluorescence could be measured in lung, liver, brain and spleen after 30 min of treatment. To model the interaction and cellular distribution of FITC-HPBCD in the wall of blood vessels, we treated human umbilical vein endothelial cells (HUVECs) with FITC-HPBCD and demonstrated for the first time that this compound could be detected in the cytoplasm in small vesicles after 30 min of treatment. FITC-HPBCD has similar pharmacokinetic to HPBCD and can provide new information to the detailed mechanism of action of HPBCD.

Encapsulation of essential oils with cyclodextrins can protect their active compounds from environmental conditions and improve their aqueous solubility, hence increasing their functional capabilities as additives. The purpose of this study was to characterize the physico-chemical properties and bio-efficacies, antioxidant and antibacterial activities, of the encapsulated black pepper essential oil in hydroxypropyl-β-cyclodextrin (HPβCD), in comparison with the major ingredient in the oil, β-caryophyllene. The difference in encapsulation efficiency of the pure compound and the black pepper oil results from the presence of other components in the black pepper oil such as limonene, δ-3-carene and pinene. Although the inclusion complexes increase their stability, they gave slightly lower antioxidant activity as a result of the HPβCD was blocking the functional groups of active compounds during reaction with DPPH radicals. Instead, after encapsulated in HPβCD, the antibacterial activity of black pepper oil was improved by 4 times against both S. aureus and E. coli . [ABSTRACT FROM AUTHOR]

In this work, hybrid gliadin electrospun fibers containing inclusion complexes of ferulic acid (FA) with hydroxypropyl-beta-cyclodextrins (FA/HP-β-CD-IC) were prepared as a strategy to increase the stability and solubility of the antioxidant FA. Inclusion complex formation between FA and HP-β-CD was confirmed by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimeter (DSC), and X-ray diffraction (XRD). After adjusting the electrospinning conditions, beaded-free fibers of gliadin incorporating FA/HP-β-CD-IC with average fiber diameters ranging from 269.91 ± 73.53 to 271.68 ± 72.76 nm were obtained. Control gliadin fibers containing free FA were also produced for comparison purposes. The incorporation of FA within the cyclodextrin molecules resulted in increased thermal stability of the antioxidant compound. Moreover, formation of the inclusion complexes also enhanced the FA photostability, as after exposing the electrospun fibers to UV light during 60 min, photodegradation of the compound was reduced in more than 30%. Moreover, a slower degradation rate was also observed when compared to the fibers containing the free FA. Results from the release into two food simulants (ethanol 10% and acetic acid 3%) and PBS also demonstrated that the formation of the inclusion complexes successfully resulted in improved solubility, as reflected from the faster and greater release of the compounds in the three assayed media. Moreover, in both types of hybrid fibers, the antioxidant capacity of FA was kept, thus confirming the suitability of electrospinning for the encapsulation of sensitive compounds, giving raise to nanostructures with potential as active packaging structures or delivery systems of use in pharmaceutical or biomedical applications.

• Zein/HP-β-CD nanoparticles enable encapsulate, protect and deliver curcumin. • Crystal curcumin was successfully entrapped into zein/HP-β-CD. • Curcumin-zein/HP-β-CD displayed excellent stability and anti-oxidation efficacy. • A novel delivery system for low water-soluble bioactive substances was designed. In this study, zein/hydroxypropyl-beta-cyclodextrin nanoparticles (ZHNPs) were synthesized using a combination of antisolvent co-precipitation and electrostatic attraction. The structural and physicochemical properties of the NPs were characterized using a variety of analytical methods. NPs with small mean diameters (143.6 nm) and strong cationic surface potentials (+62.1 mV) could be obtained at a mass ratio of zein-to-HP-β-CD of 1:1. These NPs were then used to encapsulate a model hydrophobic nutraceutical, curcumin. The results of zeta-potential, Fourier-transform infrared spectroscopy, X-ray diffractometry, and fluorescence spectroscopy measurements suggested that electrostatic, hydrogen bonding, and hydrophobic interactions were the main driving forces for NPs formation and curcumin encapsulation. The NPs had a relatively high encapsulation efficiency (89.41 %) for curcumin and improved its antioxidant activity (3.6-fold that of free curcumin) and photostability. Consequently, they could be used as effective food-grade delivery systems for low water-soluble bioactive substances. [ABSTRACT FROM AUTHOR]

This work aims to develop the herbal oil-incorporated nanostructure mats with antifungal activity for the prevention and treatment of Candida-associated denture stomatitis. The nanofiber mats loaded with betel oil or clove oil were fabricated via electrospinning process. The morphologies and physicochemical properties of the herbal oil loaded nanofiber mats were examined using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), and mechanical testing. The release characteristic, antifungal activity, and cytotoxicity were also investigated. The SEM images confirmed the homogeneous and smooth nanoscale fibers. The addition of the herbal oil into the nanofiber mats reduced the fiber diameters. The DSC and FT-IR results confirmed the presence of the oil in the nanofiber mats. The herbal oils can be released from the mats in a very fast manner and inhibit the growth of candida cells within only few minutes after contact. These nanofiber mats may be beneficial for the prevention and treatment of denture stomatitis. [ABSTRACT FROM AUTHOR]

Cyclodextrin-inclusion complexes (CD-ICs) possess great prominence in food and pharmaceutical industries due to their enhanced ability for stabilization of active compounds during processing, storage and usage. Here, CD-IC of gallic acid (GA) with hydroxypropyl-beta-cyclodextrin (GA/HPβCD-IC) was prepared and then incorporated into polylactic acid (PLA) nanofibers (PLA/GA/HPβCD-IC-NF) using electrospinning technique to observe the effect of CD-ICs in the release behavior of GA into three different mediums (water, 10% ethanol and 95% ethanol). The GA incorporated PLA nanofibers (PLA/GA-NFs) were served as control. Phase solubility studies showed an enhanced solubility of GA with increasing amount of HPβCD. The detailed characterization techniques (XRD, TGA and 1 H-NMR) confirmed the formation of inclusion complex between GA and HPβCD. Computational modeling studies indicated that the GA made an efficient complex with HPβCD at 1:1 either in vacuum or aqueous system. SEM images revealed the bead-free and uniform morphology of PLA/GA/HPβCD-IC-NF. The release studies of GA from PLA/GA/HPβCD-IC-NF and PLA/GA-NF were carried out in water, 10% ethanol and 95% ethanol, and the findings revealed that PLA/GA/HPβCD-IC-NF has released much more amount of GA in water and 10% ethanol system when compared to PLA/GA-NF. In addition, GA was released slowly from PLA/GA/HPβCD-IC-NF into 95% ethanol when compared to PLA/GA-NF. It was also observed that electrospinning process had no negative effect on the antioxidant activity of GA when GA was incorporated in PLA nanofibers. [ABSTRACT FROM AUTHOR]

A novel drug carrier based on hydroxypropyl-β-cyclodextrin (HP-β-CD) modified carboxylated graphene oxide (GO-COOH) was designed to incorporate anti-cancer drug paclitaxel (PTX). The formulated nanomedicines were characterized by Fourier transform infrared spectroscopy (FTIR) and atomic force microscopy (AFM). Results showed that PTX can be incorporated into GO-COO-HP-β-CD nanospheres successfully, with an average diameter of about 100 nm. The solubility and stability of PTX-loaded GO-COO-HP-β-CD nanospheres in aqueous media were greatly enhanced compared with the untreated PTX. The results of hemolysis test demonstrated that the drug-loaded nanospheres were qualified with good blood compatibility for intravenous use. In vitro anti-tumor activity was measured and results demonstrated that the incorporation of PTX into the newly developed GO-COO-HP-β-CD carrier could confer significantly improved cytotoxicity to the nanosystem against tumor cells than single application of PTX. GO-COO-HP-β-CD nanospheres may represent a promising formulation platform for a broad range of therapeutic agent, especially those with poor solubility. [ABSTRACT FROM AUTHOR]

In this study, an environmentally friendly compound, hydroxypropyl-beta-cyclodextrin (HP-β-CD) was applied to clean reverse osmosis (RO) membranes fouled by microorganisms. The cleaning with HP-β-CD removed the biofilm and resulted in a flux recovery ratio (FRR) of 102%. As cleaning efficiency is sometimes difficult to determine using flux recovery data alone, attached bacterial cells and extracellular polymeric substances (EPS) were quantified after cleaning the biofouled membrane with HP-β-CD. Membrane surface characterization using scanning electron microscopy (SEM), attenuated total reflectance Fourier transform infrared (ATR-FTIR) and atomic force microscopy (AFM) confirmed the effectiveness of HP-β-CD in removal of biofilm from the RO membrane surface. Finally, a comparative study was performed to investigate the competitiveness of HP-β-CD with other known cleaning agents such as sodium dodecyl sulfate (SDS), ethylenediaminetetraacetic acid (EDTA), Tween 20, rhamnolipid, nisin, and surfactin. In all cases, HP-β-CD was superior. [ABSTRACT FROM PUBLISHER]

The pressure ulcer healing is a complex process and difficult to be achieved. Insulin is known to promote wound healing, and when complexed with cyclodextrin presents improved solubility, stability and biological activity. Complexation of insulin with hydroxypropyl-beta-cyclodextrin (HPβCD) was performed in this work through the coprecipitation method, providing the inclusion complex (HPβCD–I). The spectroscopic techniques used to analyze the complex were H 1 NMR, FT-Raman and FT-IR/ATR. A gel containing the HPβCD–I complex was prepared and a clinical study was conducted in patients with pressure ulcers. The spectroscopic techniques allowed to confirm the complex formation through the inclusion of aromatic amino acids, such as phenylalanine present in the HPβCD cavity. Data obtained from the FT-Raman and FT-IR/ATR techniques, combined with the H 1 NMR results, showed the effectiveness of these techniques in evaluating the inclusion complex of HPβCD with insulin. Clinical studies demonstrated tissue revitalization and a trend ( p = 0.06) for a significant difference between the healing effect of the control gel and that with HPβCD–I complex. The creation of the gel prepared with insulin and HPβCD–I complex and its use in patients with pressure ulcers appears to be promising in wound healing and its possible use in hospital care. [ABSTRACT FROM AUTHOR]

This study was conducted to assess the safety and tolerability of the alternative formulation vehicles polysorbate 80 (PS80), propylene glycol (PG), and hydroxypropyl-beta-cyclodextrin (HPβCD) in general toxicology studies in the mouse, rat, dog, and monkey. Twenty (20) mg/kg of hydroxypropyl methylcellulose (MC, control), 10 mg/kg PS80, 1000 mg/kg PG, 500 mg/kg HPβCD, or 1000 mg/kg HPβCD were administered by oral gavage to mice, rats, dogs, and cynomolgus monkeys for approximately 90 days. The effects of these formulations on clinical observations, body weight and food consumption parameters, clinical pathology, and histopathology were evaluated across all species. The suitability of formulations containing up to 20 mg/kg MC, 10 mg/kg PS80, and 1000 mg/kg PG for use in preclinical safety studies was confirmed by a lack of effects on all parameters examined. However, formulations containing HPβCD produced elevated transaminase (aspartate and alanine aminotransferase) levels in rats and mice and fecal changes (loose and soft stool) in large animals. Although the etiology and toxicological significance of the transaminase elevations in rats and mice is uncertain, this finding could represent a significant liability for a preclinical formulation because of the critical importance of these biomarkers in the risk assessment of novel therapeutic agents. Based on these data, PS80 and PG are considered to be practical alternatives to MC in preclinical toxicology studies. However, formulations containing HPβCD should be used with caution because of the elevations in rodent transaminase levels. [ABSTRACT FROM AUTHOR]

Mucopolysaccharidosis type II (MPS II), also known as Hunter syndrome, is a rare, lysosomal disorder caused by mutations in a gene encoding iduronate-2-sulfatase (IDS). IDS deficiency results in an accumulation of glycosaminoglycans (GAGs) and secondary accumulations of other lipids in lysosomes. Symptoms of MPS II include a variety of soft and hard tissue problems, developmental delay, and deterioration of multiple organs. Enzyme replacement therapy is an approved treatment for MPS II, but fails to improve neuronal symptoms. Cell-based neuronal models of MPS II disease are needed for compound screening and drug development for the treatment of the neuronal symptoms in MPS II. In this study, three induced pluripotent stem cell (iPSC) lines were generated from three MPS II patient-derived dermal fibroblast cell lines that were differentiated into neural stem cells and neurons. The disease phenotypes were measured using immunofluorescence staining and Nile red dye staining. In addition, the therapeutic effects of recombinant human IDS enzyme, delta-tocopherol (DT), and hydroxypropyl-beta-cyclodextrin (HPBCD) were determined in the MPS II disease cells. Finally, the neural stem cells from two of the MPS II iPSC lines exhibited typical disease features including a deficiency of IDS activity, abnormal glycosaminoglycan storage, and secondary lipid accumulation. Enzyme replacement therapy partially rescued the disease phenotypes in these cells. DT showed a significant effect in reducing the secondary accumulation of lipids in the MPS II neural stem cells. In contrast, HPBCD displayed limited or no effect in these cells. Our data indicate that these MPS II cells can be used as a cell-based disease model to study disease pathogenesis, evaluate drug efficacy, and screen compounds for drug development. • A neuronal cell model of MPS II derived from patient iPSCs is useful for evaluation of drug efficacy. • MPS II neuronal cells has disease phenotypes of enlarged lysosomes and secondary lipid accumulation. • Recombinant human IDS enzyme and δ-tocopherol reduced the disease phenotypes in MPS II cells. [ABSTRACT FROM AUTHOR]

Abstract: (+)-Catechin (CAT) was considered as a polyphenolic compound abundantly contained in plants. It exerts protective effect against cancer, inflammatory and cardiovascular diseases. These protective effects are mainly attributed to its antioxidative activity by scavenging free radicals. Therefore, the need of simple, selective and sensitive monitoring of (+)-catechin in commercial drinks and biological fluids is crucial. A new selective and sensitive voltammetric quantification of (+)-catechin was investigated at low cost hydroxypropyl-beta-cyclodextrin modified carbon paste sensor in acidic solutions. The constructed sensor was treated in simple and fast manner to increase its stability for catechin determination. The effect of solution and instrumental parameters was investigated by using osteryoung square-wave anodic voltammetry (OSWAV) at pH 2.20 and differential pulse cathodic voltammetry (DPCV) at pH 4.40 in 0.10M Britton-Robinson buffer. Acidic solutions were chosen to increase the stability of (+)-catechin, reduce its adsorption on the sensor surface and increase the selectivity of proposed method. Cyclic voltammetry (CV) was used to elucidate the electrochemical mechanism of catechin at the modified electrochemical sensor. A linear range up to 7.20 and 4.20μgmL−1 of catechin was achieved in anodic and cathodic voltammetry, respectively. The method gave reproducible and reliable results with 1.50(gmL−1 catechin (S.D. 0.062). Limit of detection of 0.12 and 0.30ngmL−1 and limit of quantification (LOQ) of 1.10 and 2.80ngmL−1 were easily achieved using anodic and cathodic voltammetry, respectively. Selectivity of the proposed procedure was estimated by testing recovery and adding the most interfering metal ions and/or organic compounds. The proposed method was applied successfully to selective determination of catechin in some commercial drinks like tea, cocoa and coffee with acceptable recovery range (98–102%). The extraction of catechin was rather simple, making it suitable for studies with a large number of commercial samples. Furthermore, the application to urine samples without pretreatment was achieved and statistically confirmed at 95% confidence level. It was easy to analyze catechin in urine down to 0.55ngmL−1. [Copyright &y& Elsevier]

Abstract: The chiral separation of norgestrel enantiomers using reversed-phase high-performance liquid chromatography (RP-HPLC) was studied with hydroxypropyl-beta-cyclodextrin (HP-beta-CD) as chiral mobile phase additive. The effect of mobile phase composition, concentration of HP-beta-CD and column temperature on enantioselective separation were investigated. The quantification properties of the developed RP-HPLC method were examined. A baseline separation of norgestrel enantiomers was achieved on a Agilent ZORBAX Eclipse XDB-C8 column (150mm×4.6mm i.d., 5μm). The mobile phase was a mixture of acetonitrile and phosphate buffer (pH 5.0, 20mM) containing 25mM HP-beta-CD (30:70, v/v) with a flow rate of 1.0ml/min. The UV detector was set at 240nm. Calibration curves were linear (n =8) in the range of 0.2–25μg/ml, the limit of detection and quantitation were 0.10 and 0.20μg/ml, respectively, for racemic norgestrel. The values of RSD of repeatability and intermediate precision for spiked sample were less than 4.8%. The method was successfully applied to the enantioselective determination of this drug in stereoselective skin permeation study. [Copyright &y& Elsevier]

Bupranolol (BPL) is a potent beta-blocking agent, the extensive first-pass metabolism (>90%) and rapid elimination half-life (1.5–2.0 h) of this drug make it well suited to be developed as a transdermal delivery system (TDS). Hydroxypropyl βCD (HPβCD) and partially methylated βCD (PMβCD) were used as penetration enhancers for BPL. The formation of inclusion complex of BPL with these cyclodextrins (CDs) was characterized in solution and solid states by phase solubility, X-ray diffractometry and differential scanning calorimetry (DSC) analyses. The effect of CDs on the permeation enhancement of BPL through rat skin was studied using side-by-side diffusion cells and pH 7.4 phosphate-buffered saline (PBS). CDs were employed at different concentrations with 0.4% (w/v) BPL as well as with excess quantity of BPL (1.0%, w/v) that CDs could not complex all the BPL and the drug was in the form of an aqueous suspension. The permeation of BPL from its aqueous suspension (0.4%, w/v) significantly increased when CDs were used at low concentrations (up to 2 and 5%, w/v concentration for HPβCD and PMβCD, respectively) (P<0.01). At higher CD concentrations, the permeation of BPL decreased; and both CDs at 10% (w/w), showed similar flux values to that of control (no enhancer, P>0.05). The permeation of BPL from its 1.0% (w/v) aqueous suspension increased with increase in concentration of CD up to 10% (w/v) for HPβCD and PMβCD. At 10% (w/v) concentration of HPβCD and PMβCD, the flux of BPL from its 1.0% aqueous suspension increased 3.8- and 4.6-fold (P<0.01 and P<0.001, respectively). The permeation data of skin pretreatment with CDs indicate that HPβCD had no effect on the skin, whereas PMβCD significantly reduced the skin barrier for BPL, as shown by 1.7-fold increase in the flux by PMβCD pretreatment (P<0.001). Overall, both HPβCD and PMβCD were found to be suitable for improving the solubility and penetration enhancement of BPL. [Copyright &y& Elsevier]

In this study, we are introducing a method that can effectively stabilize antioxidants in water-in-oil-in-water (W/O/W) double emulsions. Preliminarily, stable W/O/W double emulsions were produced by manipulating the characteristics of internal aqueous phase via two-stage emulsification, resulting consequently in the formation of fine internal water droplets in the dispersed oil droplets. From conductivity measurements that can determine the elution amount of internal aqueous phase, it was confirmed that the double emulsion stability could be improved by treating the internal aqueous phase with a hydroxypropyl-beta-cyclodextrin. In this study, kojic acid, 5-hydroxy-2-(hydroxymethyl)-4-pyrone was selected as a model antioxidant. The stabilization of kojic acid was attempted by locating it in the internal water droplets of the stable W/O/W double emulsions. The stability of kojic acid in the double emulsion system could be maintained at 90% for 10 weeks at high temperature. We believe that these stable W/O/W double emulsions could be used meaningfully as a carrier for many unstable antioxidants. [ABSTRACT FROM AUTHOR]

Poly(ethylcyanoacrylate) (PECA) nanospheres have been employed as biodegradable polymeric carriers for oral (po) delivery of insulin. The main goal of this investigation was to screen various absorption enhancers, which were used to protect insulin-loaded PECA, by following their in vivo performance after oral administrations to streptozotocin-induced diabetic rats. The nanospheres were prepared by polymerization in a continuous aqueous phase at pH 2.5 and in the presence of Pluronic 68 (0.5%). This polymerization technique was able to hold 85 ± 7.5% of insulin added, 30 min after initiation of polymerization. The drug loading was evaluated by HPLC. Insulin absorption after oral administration was evaluated by its hypoglycemic effect. The addition of protease inhibitor to insulin-loaded PECA nanospheres significantly reduced the blood glucose level after po administrations. Capric acid (0.5%) showed the maximum reduction in blood glucose level (bG[sub max] = 34.4 ± 4.1 mg%), while cholic acid (0.5%) showed the fastest reduction in blood glucose level (T[sub max,G] = 6.0 ± 0.2 h) among the tested oral absorption enhancers. Insulin associated with PECA nanospheres retained its biological activity up to 12 days in 50% of the rats in the presence of glycyrrhizic acid (1%). The per cent pharmacological availabilities (PA%) were in the order of capric acid (0.5%) > glycyrrhizic acid (1%) > deoxycholic acid (0.5%) > hydroxypropyl-β-cyclodextrin (HPβCD) (1%) > cholic acid (0.5%). There was no significant difference in the PA% between capric acid (0.5%), glycyrrhizic acid (1%) and deoxycholic acid (0.5%). Although sodium cholate (0.5%) showed the lowest increase in PA% (3.1 ± 3.1%), its T[sub max,G] was the shortest (6 ± 0.2 h) among the tested absorption enhancers. The reduction in blood glucose levels was maintained < 200 mg/dL in the order of glycyrrhizic acid (166 ± 56 h) > capric acid (72 h) > deoxycholic acid (66 ± 6 h) > no enhancer (64 ± 16 h) > HPβCD (31 ± 17.5) > cholic acid (22 ± 5.7 h) > aprotenin (20 ± 3.5 h). Therefore, capric acid and glycyrrhizic acid could be successfully used as oral absorption enhancers. [ABSTRACT FROM AUTHOR]