Encapsulation of antioxidant beta-carotene by cyclodextrin complex electrospun nanofibers: Solubilization and stabilization of beta-carotene by cyclodextrins.

Carotenoids act as effective antioxidant defense systems in humans as they scavenge molecular oxygen and peroxyl radicals. However, their poor water solubility and being susceptible to degradation driven by light and oxygen hinder their bioactivity, therefore, they should be stabilized by host matrices against oxidation. Here, ß-carotene was encapsulated in electrospun cyclodextrin (CD) nanofibers to increase its water-solubility and photostability to enhance its antioxidant bioactivity. ß-carotene/CD complex aqueous solutions were electrospun into nanofibers. The bead-free morphology of the ß-carotene/CD nanofibers was confirmed by SEM. The formation of ß-carotene/CD complexes was explored through computational modeling and experimentally by FTIR, XRD and solubility tests. The antioxidant activity of the fibers exposed to UV irradiation was demonstrated via a free radical scavenger assay, where ß-carotene/CD nanofibers revealed protection against UV radiation. Overall, this work reports the water-borne electrospinning of antioxidant ß-carotene/CD inclusion complex nanofibers, which stabilize the encapsulated ß-carotene against UV-mediated oxidation.

Investigation of the Effect of Radiotherapy Dose on Chewing and Swallowing Structures in Head and Neck Cancer Patients Treated with Concomitant Chemoradiotherapy.

Intensity-modulated radiotherapy (IMRT) is a treatment method that is used in the treatment of head and neck cancers. Impairment of chewing and swallowing functions in the early and late periods of radiotherapy is frequent. Therefore, revealing the dose-effect relationship is important. The main purpose of this study is to investigate the dose-effect relationship between chewing and swallowing structures objectively via a standardized videofluoroscopy protocol. The study included 35 participants treated with chemo-IMRT. A videofluoroscopic swallowing study (VFSS) was performed before IMRT, and 3 and 6 months after IMRT. VFSS results were scored according to the Modified Barium Swallow Impairment Profile (MBSImP) and the Penetration-Aspiration Scale (PAS). Maximum interincisor mouth opening, body mass index (BMI), and Functional Oral Intake Scale levels were determined in these cases. The quality of life of participants was evaluated. There was a significant increase in PAS and MBSImP scores and a significant decrease in BMI scores of the patients after treatment. Xerotomy and sticky saliva complaints increased after treatment. The dose to the mastication muscles (> 40 Gy) and the temporomandibular joint (> 46 Gy) were found to be associated with a decrease in BMI; the dose to the superior pharyngeal constructor muscle (> 58 Gy) was found to be associated with pharyngeal stripping wave. The presence of aspiration was associated with the inferior pharyngeal constructor muscle, glottic larynx, supraglottic larynx, and upper esophageal sphincter. Important findings to emerge from this study include detected toxic dose limits. These findings may guide physicians to minimize the side effects of IMRT.

Colon targeted delivery of niclosamide from ß-cyclodextrin inclusion complex incorporated electrospun Eudragit® L100 nanofibers.

Electrospun nanofibers incorporated with inclusion complex (IC) of niclosamide (NIC) and hydroxypropyl-beta-cyclodextrin (HPßCD) (NIC-HPßCD-IC) was produced from pH-responsive polymer (Eudragit® L100, EUD), which disintegrates at pH values higher than 6, (EUD-NIC-HPßCD-IC-NF) for targeted delivery of NIC to the colon. Pristine EUD nanofibers (EUD-NF), only NIC loaded (EUD-NIC-NF) and physical mixture of NIC and HPßCD loaded EUD nanofibers (EUD-NIC-HPßCD-NF) were also produced as reference. SEM images revealed the bead-free and uniform morphology of nanofibers. XRD, TGA, and DSC were also performed for both NIC-HPßCD-IC and electrospun nanofibers and it was seen that there are some NIC molecules, which cannot make IC. Dissolution studies were carried out for 240 min at pH 1.2 and pH 7 simulating stomach and colon, respectively. EUD-NIC-NF released almost 53 % of NIC in 120 min, whereas EUD-NIC-HPßCD-NF (15 %) and EUD-NIC-HPßCD-IC-NF (8 %) released at most 15 % of NIC in 120 min. Then, remained NIC in the nanofibers released into the colon for the next 120 min. The slight difference in the release of NIC into stomach from EUD-NIC-HPßCD-NF and EUD-NIC-HPßCD-IC-NF might be due to the uncomplexed NIC molecules in EUD-NIC-HPßCD-IC-NF. More importantly, EUD-NIC-HPßCD-IC-NF was quite effective for preventing the release of NIC in the stomach in contrast to EUD-NIC-NF, which has already released more than half amount of NIC in 120 min. In conclusion, this study might open new areas for developing targeted delivery systems by the combination of nanofibers and CD-ICs for hydrophobic drugs such as NIC.

Factors affecting post-treatment radiation-induced lung disease in patients receiving stereotactic body radiotherapy to lung.

The aim of the study is to investigate factors that may cause radiation-induced lung disease (RILD) in patients undergoing stereotactic body radiotherapy (SBRT) for lung tumors. Medical records of patients treated between May 2018 and June 2019 with SBRT were retrospectively evaluated. All patients should have a diagnosis of either primary non-small cell lung cancer (NSCLC) or less than three metastases to lung from another primary. The median treatment dose was 50 Gy in 4-5 fractions. Tumor response and RILD were evaluated in thoracic computer tomography (CT) using RECIST criteria. 82 patients with 97 lung lesions were treated. The median age was 68 years (IQR = 62-76). With a median follow-up of 7.2 months (3-18 months), three patients had grade 3 radiation pneumonitis (RP). RILD was observed in 52% of cases. Patients who had RILD had a higher risk of symptomatic RP (p = 0.007). In multivariate analyses older age, previous lung radiotherapy history, and median planning treatment volume (PTV) D95 value of ≥ 48 Gy were associated with RILD. Local recurrence (LR) was observed in 5.1% of cases. There was no difference in overall survival and LR with the presence of RILD. Older age, previous lung radiotherapy history, and median PTV D95 value of ≥ 48 Gy seems to be associated with post-SBRT RILD.

Molecular Encapsulation of Cinnamaldehyde within Cyclodextrin Inclusion Complex Electrospun Nanofibers: Fast-Dissolution, Enhanced Water Solubility, High Temperature Stability, and Antibacterial Activity of Cinnamaldehyde.

The electrospinning of nanofibers (NFs) of cinnamaldehyde inclusion complexes (ICs) with two different hydroxypropylated cyclodextrins (CDs), hydroxypropyl-ß-cyclodextrin (HP-ß-CD) and hydroxypropyl-γ-cyclodextrin (HP-γ-CD), was successfully performed in order to produce cinnamaldehyde/CD-IC NFs without using an additional polymer matrix. The inclusion complexation between cinnamaldehyde and hydroxypropylated CDs was studied by computational molecular modeling, and the results suggested that HP-ß-CD and HP-γ-CD can be inclusion complexed with cinnamaldehyde at 1:1 and 2:1 (cinnamaldehyde/CD) molar ratios. Additionally, molecular modeling and phase solubility studies showed that water solubility of cinnamaldehyde dramatically increases with cyclodextrin inclusion complex (CD-IC) formation. The HP-ß-CD has shown slightly stronger binding with cinnamaldehyde when compared to HP-γ-CD for cinnamaldehyde/CD-IC. Although cinnamaldehyde is a highly volatile compound, it was effectively preserved with high loading by the cinnamaldehyde/CD-IC NFs. It was also observed that cinnamaldehyde has shown much higher temperature stability in cinnamaldehyde/CD-IC NFs compared to uncomplexed cinnamaldehyde because of the inclusion complexation state of cinnamaldehyde within the hydroxypropylated CD cavity. Moreover, cinnamaldehyde still has kept its antibacterial activity in cinnamaldehyde/CD-IC NF samples when tested against Escherichia coli. In addition, cinnamaldehyde/CD-IC NF mats were fast-dissolving in water, even though pure cinnamaldehyde has a water-insoluble nature. In brief, self-standing nanofibrous mats of electrospun cinnamaldehyde/CD-IC NFs are potentially applicable in food, oral-care, healthcare, and pharmaceutics because of their fast-dissolving character, enhanced water solubility, stability at elevated temperature, and promising antibacterial activity.

Efficient Removal of Polycyclic Aromatic Hydrocarbons and Heavy Metals from Water by Electrospun Nanofibrous Polycyclodextrin Membranes.

Here, a highly efficient membrane based on electrospun polycyclodextrin (poly-CD) nanofibers was prepared and exploited for the scavenging of various polycyclic aromatic hydrocarbons (PAHs) and heavy metals from water. The poly-CD nanofibers were produced by the electrospinning of CD molecules in the presence of a cross-linker (i.e., 1,2,3,4-butanetetracarboxylic acid), followed by heat treatment to obtain an insoluble poly-CD nanofibrous membrane. The membrane was used for the removal of several PAH compounds (i.e., acenaphthene, fluorene, fluoranthene, phenanthrene, and pyrene) and heavy metals (i.e., Pb2+, Ni2+, Mn2+, Cd2+, Zn2+, and Cu2+) from water over time. Experiments were made on the batch sorption of PAHs and heavy metals from contaminated water to explore the binding affinity of PAHs and heavy metals to the poly-CD membrane. The equilibrium sorption capacity (q e) of the poly-CD nanofibrous membrane was found to be 0.43 ± 0.045 mg/g for PAHs and 4.54 ± 0.063 mg/g for heavy metals, and the sorption kinetics fitted well with the pseudo-second-order model for both types of pollutants. The membrane could be recycled after treatment with acetonitrile or a 2% nitric acid solution and reused up to four times with similar performance. Further, dead-end filtration experiments showed that the PAH removal efficiencies were as high as 92.6 ± 1.6 and 89.9 ± 4.8% in 40 s for the solutions of 400 and 600 µg/L PAHs, respectively. On the other hand, the removal efficiencies for heavy metals during the filtration were 94.3 ± 5.3 and 72.4 ± 23.4% for 10 and 50 mg/L solutions, respectively, suggesting rapid and efficient filtration of heavy metals and PAHs by the nanofibrous poly-CD membrane.

One-step green synthesis of antibacterial silver nanoparticles embedded in electrospun cyclodextrin nanofibers.

Antibacterial electrospun nanofibers based on cyclodextrin (CD) and silver nanoparticles (Ag-NPs) were produced by solution electrospinning from aqueous and DMF solutions using different Ag contents. CD molecules acted as the reducing agent and catalyzed the formation of Ag-NPs. The nanofibers with smaller diameters were observed for the fibers generated from DMF solutions than those produced from aqueous solutions. TEM and STEM analyses revealed the Ag-NPs (∼2-5 nm depending on solvent-type and Ag loading) in nanofibers, while FTIR and surface enhanced Raman scattering (SERS) analyses showed the apparent frequency shift of OH stretching band and the enhancement of Raman bands of CD molecules with the incorporation of the Ag-NPs. The polycrystalline structure of the Ag-NPs was shown by XRD and SAED analyses over {111}, {200}, {220} and {311} planes. The nanofibers showed significant inhibition against the growth of Escherichia coli and Staphylococcus aureus owing to the antibacterial activity of the Ag-NPs.

Efficient Encapsulation of Citral in Fast-Dissolving Polymer-Free Electrospun Nanofibers of Cyclodextrin Inclusion Complexes: High Thermal Stability, Longer Shelf-Life, and Enhanced Water Solubility of Citral.

Here, we report a facile production of citral/cyclodextrin (CD) inclusion complex (IC) nanofibers (NFs) from three types of CDs (hydroxypropyl-beta-cyclodextrin (HPßCD), hydroxypropyl-gamma-cyclodextrin (HPγCD), and methylated-beta-cyclodextrin (MßCD)) by an electrospinning technique without the need of any polymeric carrier matrix. Self-standing nanofibrous webs of citral/CD-IC nanofibers (citral/CD-IC-NF) with uniform fiber morphology have been successfully electrospun from aqueous solutions of citral/CD-IC. Thanks to the inclusion complex formed with CDs, the efficient preservation of citral (up to ~80%) in citral/CD-IC-NFs was observed. In addition, the citral/CD-IC-NFs have shown ~50% preservation of citral for 15 days at room temperature even though citral has a highly volatile nature. The enhanced thermal stability of citral (~100⁻300°C) in citral/CD-IC-NFs compared to pure citral (~50⁻165°C) has been observed. Moreover, citral/CD-IC-NFs tended to disintegrate in water very quickly. To summarize, citral was efficiently encapsulated in citral/CD-IC-NFs, and these citral/CD-IC-NFs have been shown to be fast dissolving. In citral/CD-IC-NFs, citral/CD-ICs have enhanced water solubility of citral along with high-temperature stability and a longer shelf-life.

Thymol/cyclodextrin inclusion complex nanofibrous webs: Enhanced water solubility, high thermal stability and antioxidant property of thymol.

The development of novel nanomaterials that provide an efficient encapsulation and protection for the active food additives is one of the main focuses of current research efforts at food application areas. From this point of view, in this study, nanofibrous webs from inclusion complexes (IC) of modified cyclodextrins (hydroxypropyl-ß-cyclodextrin (HPßCD), hydroxypropyl-γ-cyclodextrin (HPγCD) and methyl-ß-cyclodextrin (MßCD)) and essential oils compound (i.e. thymol) was produced through electrospinning technique. While pure thymol has a highly volatile nature, the volatility of thymol was effectively suppressed by the inclusion complexation and ~88-100% (w/w) of thymol was preserved in electrospun thymol/cyclodextrin inclusion complex nanofibers (Thymol/CD-IC NF). The aqueous solubility enhancement for hydrophobic thymol was demonstrated by phase solubility diagram which also suggested the 1:1M inclusion complexation between thymol and CD molecules. Besides, Thymol/CD-IC NF displayed quite fast disintegration in water compared to poorly water soluble thymol. By inclusion complexation, high temperature stability for volatile thymol was achieved for Thymol/CD-IC NF samples. The loading of thymol in Thymol/CD-IC NF conferred DPPH radical scavenging ability to these nanofibrous webs. So, the Thymol/CD-IC NF have shown antioxidant activity along with enhanced water solubility and high thermal stability of thymol. In brief, encapsulation of essential oil compounds such as thymol in electrospun CD-IC nanofibers can promote its potential application in food and oral-care products by associating the large surface area of nanofibrous webs along with CD inclusion complexation which provides enhanced water solubility and antioxidant property, and high temperature stability for thymol.

Fabrication of Electrospun Eugenol/Cyclodextrin Inclusion Complex Nanofibrous Webs for Enhanced Antioxidant Property, Water Solubility, and High Temperature Stability.

In this study, inclusion complexes (IC) of three cyclodextrin derivatives (HP-ß-CD, HP-γ-CD, and M-ß-CD) with eugenol (essential oil compound) were formed in highly concentrated aqueous solutions and then transformed into self-standing functional nanofibrous webs by electrospinning. The improved aqueous solubility of eugenol was confirmed by phase solubility diagrams, in addition, the phase solubility tests also revealed 1:1 molar ratio complexation between host:guest molecules; CD:eugenol. Even though eugenol has a volatile nature, a large amount of eugenol (∼70-95%) was preserved in eugenol/cyclodextrin inclusion complex nanofibrous webs (eugenol/CD/IC-NW). Moreover, enhanced thermal stability of eugenol was recorded for eugenol/CD/IC-NW (up to ∼310 °C) when compared to pure form of eugenol (up to ∼200 °C). The eugenol/CD/IC-NW exhibited fast dissolving behavior in water, contrary to poorly water-soluble eugenol. It was observed that the complexation between M-ß-CD and eugenol was the strongest when compared to other two host CD molecules (HP-ß-CD and HP-γ-CD) for eugenol/CD/IC-NW samples. The electrospun eugenol/CD/IC-NW samples have shown enhanced antioxidant activity compared to pure form of eugenol. In summary, cyclodextrin inclusion complexes of essential oil compounds, such as eugenol, in the form of self-standing nanofibrous webs may have potentials for food and oral-care applications due to their particularly large surface area along with fast-dissolving character, improved water solubility, high temperature stability, and enhanced antioxidant activity.

Electrospun crosslinked poly-cyclodextrin nanofibers: Highly efficient molecular filtration thru host-guest inclusion complexation.

Water pollution is a serious concern for public health and environment in today's world; hence, there exists a strong demand to develop cost-effective, sustainable and eco-friendly membranes. Here, we produce a highly efficient molecular filter membrane based on bio-renewable material; cyclic oligosaccaharides known as cyclodextrins (CD). Crosslinked insoluble poly-CD nanofibers are produced by using electrospinning technique in the absence of any additional polymeric carrier. Poly-CD nanofibrous membrane exhibit significant affinity to a common class of organic pollutant (i.e. methylene blue (MB)). Remarkably, the electrospun poly-CD nanofibrous web can outdistance the commonly used filter material (i.e. activated carbon) in terms of removal capacity. The flexible and free-standing poly-CD nanofibrous membrane depicted outstanding filtration performance. We estimate of above 90% removal efficiency for highly concentrated solutions of MB pollutant (40 mg/L) under extremely high flux (3840 Lm-2h-1). Essentially, these poly-CD nanofibrous webs demonstrate quite rapid uptake of MB from liquid environment. Overall, bio-based flexible electrospun poly-CD nanofibrous membrane represents a highly efficient molecular filter for wastewater treatment.

Polymer-free electrospun nanofibers from sulfobutyl ether7-beta-cyclodextrin (SBE7-ß-CD) inclusion complex with sulfisoxazole: Fast-dissolving and enhanced water-solubility of sulfisoxazole.

In this study, our aim was to develop solid drug-cyclodextrin inclusion complex system having nanofibrous morphology in order to have fast-dissolving property and enhanced water-solubility of poorly water-soluble drug. Here, we prepared a highly concentrated aqueous solution of inclusion complex between sulfisoxazole and sulfobutyl ether7-beta-cyclodextrin (SBE7-ß-CD, Captisol®), and then, without using any polymeric matrix, the electrospinning of sulfisoxazole/SBE7-ß-CD-IC nanofibers was performed in order to obtain free-standing and handy nanofibrous web. As a control sample, nanofibers from pure SBE7-ß-CD was also electrospun and free-standing nanofibrous web was obtained. The SEM imaging revealed that the bead-free and uniform nanofiber morphology with the average fiber diameter (AFD) of 650±290nm for sulfisoxazole/SBE7-ß-CD-IC NF and 890±415nm for pure SBE7-ß-CD NF was obtained. The inclusion complex formation between sulfisoxazole and SBE7-ß-CD in sulfisoxazole/SBE7-ß-CD-IC NF sample was confirmed by 1H NMR, TGA, DSC, XRD and FTIR analyses. Due to the combined advantage of cyclodextrin inclusion complexation and high surface area of electrospun nanofibers, fast-dissolving property with enhanced water-solubility was successfully achieved for sulfisoxazole/SBE7-ß-CD-IC NF. Our findings suggest that electrospun nanofibers/nanowebs from CD-IC of poorly water-soluble drugs may offer applicable approaches for high water-solubility and fast-dissolving tablet formulations for drug delivery systems.

Electrospinning of cyclodextrin/linalool-inclusion complex nanofibers: Fast-dissolving nanofibrous web with prolonged release and antibacterial activity.

The volatility and limited water solubility of linalool is a critical issue to be solved. Here, we demonstrated the electrospinning of polymer-free nanofibrous webs of cyclodextrin/linalool-inclusion complex (CD/linalool-IC-NFs). Three types of modified cyclodextrin (HPßCD, MßCD, and HPγCD) were used to electrospin CD/linalool-IC-NFs. Free-standing CD/linalool-IC-NFs facilitate maximum loading of linalool up to 12% (w/w). A significant amount of linalool (45-89%) was preserved in CD/linalool-IC-NFs, due to enhancement in the thermal stability of linalool by cyclodextrin inclusion complexation. Remarkably, CD/linalool-IC-NFs have shown fast-dissolving characteristics in which these nanofibrous webs dissolved in water within two seconds. Furthermore, linalool release from CD/linalool-IC-NFs inhibited growth of model Gram-negative (E. coli) and Gram-positive (S. aureus) bacteria to a great extent. Briefly, characteristics of liquid linalool have been preserved in a solid nanofiber form and designed CD/linalool-IC-NFs confer high loading capacity, enhanced shelf life and strong antibacterial activity of linalool.

Fast-Dissolving, Prolonged Release, and Antibacterial Cyclodextrin/Limonene-Inclusion Complex Nanofibrous Webs via Polymer-Free Electrospinning.

We have proposed a new strategy for preparing free-standing nanofibrous webs from an inclusion complex (IC) of a well-known flavor/fragrance compound (limonene) with three modified cyclodextrins (HPßCD, MßCD, and HPγCD) via electrospinning (CD/limonene-IC-NFs) without using a polymeric matrix. The experimental and computational modeling studies proved that the stoichiometry of the complexes was 1:1 for CD/limonene systems. MßCD/limonene-IC-NF released much more limonene at 37, 50, and 75 °C than HPßCD/limonene-IC-NF and HPγCD/limonene-IC-NF because of the greater amount of preserved limonene. Moreover, MßCD/limonene-IC-NF has released only 25% (w/w) of its limonene, whereas HPßCD/limonene-IC-NF and HPγCD/limonene-IC-NF released 51 and 88% (w/w) of their limonene in 100 days, respectively. CD/limonene-IC-NFs exhibited high antibacterial activity against E. coli and S. aureus. The water solubility of limonene increased significantly and CD/limonene-IC-NFs were dissolved in water in a few seconds. In brief, CD/limonene-IC-NFs with fast-dissolving character enhanced the thermal stability and prolonged the shelf life along with antibacterial properties could be quite applicable in food and oral care applications.

Regio-selective chemical-enzymatic synthesis of pyrimidine nucleotides facilitates RNA structure and dynamics studies.

Isotope labeling has revolutionized NMR studies of small nucleic acids, but to extend this technology to larger RNAs, site-specific labeling tools to expedite NMR structural and dynamics studies are required. Using enzymes from the pentose phosphate pathway, we coupled chemically synthesized uracil nucleobase with specifically (13) C-labeled ribose to synthesize both UTP and CTP in nearly quantitative yields. This chemoenzymatic method affords a cost-effective preparation of labels that are unattainable by current methods. The methodology generates versatile (13) C and (15) N labeling patterns which, when employed with relaxation-optimized NMR spectroscopy, effectively mitigate problems of rapid relaxation that result in low resolution and sensitivity. The methodology is demonstrated with RNAs of various sizes, complexity, and function: the exon splicing silencer 3 (27 nt), iron responsive element (29 nt), Pro-tRNA (76 nt), and HIV-1 core encapsidation signal (155 nt).