Design of polymer-free Vitamin-A acetate/cyclodextrin nanofibrous webs: antioxidant and fast-dissolving properties.

The encapsulation of food/dietary supplements into electrospun cyclodextrin (CD) inclusion complex nanofibers paves the way for developing novel carrying and delivery substances along with orally fast-dissolving properties. In this study, CD inclusion complex nanofibers of Vitamin-A acetate were fabricated from polymer-free aqueous systems by using the electrospinning technique. The hydroxypropylated (HP) CD derivatives of HPßCD and HPγCD were used for both encapsulation of Vitamin-A acetate and the electrospinning of free-standing nanofibrous webs. The ultimate Vitamin-A acetate/CD nanofibrous webs (NWs) were obtained with a loading capacity of 5% (w/w). The amorphous distribution of Vitamin-A acetate in the nanofibrous webs by inclusion complexation and the unique properties of nanofibers (e.g. high surface area and porosity) ensured the fast disintegration and fast dissolution/release of Vitamin-A acetate/CD-NW in a saliva simulation and aqueous medium. The enhanced solubility of Vitamin-A acetate in the case of Vitamin-A acetate/CD-NW also ensured an improved antioxidant property for the Vitamin-A acetate compound. Moreover, Vitamin-A acetate thermally degraded at higher temperature in Vitamin-A acetate/CD-NWs, suggesting the enhanced thermal stability of this active compound. Here, HPßCD formed inclusion complexes in a more favorable way when compared to HPγCD. Therefore, there were some uncomplexed Vitamin-A acetate crystals detected in Vitamin-A acetate/HPγCD-NW, while Vitamin-A acetate molecules loaded in Vitamin-A acetate/HPßCD-NW were completely in complexed and amorphous states. Depending on this, better solubilizing effect, higher release amount and enhanced antioxidant properties have been provided for the Vitamin-A acetate compound in the case of Vitamin-A acetate/HPßCD-NW.

Fast-dissolving antioxidant curcumin/cyclodextrin inclusion complex electrospun nanofibrous webs.

Curcumin/Hydroxypropyl-beta-Cyclodextrin (HP-ß-CyD) and Curcumin/Hydroxypropyl-gamma-Cyclodextrin (HP-γ-CyD) inclusion complex nanofibrous webs were produced using electrospinning technique for the purpose of orally fast-dissolving antioxidant food supplement. Curcumin was totally preserved without any loss during the electrospinning process. The aqueous solutions of curcumin/HP-ß-CyD and curcumin/HP-γ-CyD were yielded uniform fiber morphology with ~200 nm and ~900 nm average fiber diameter, respectively. Both Curcumin/CyD webs were produced in the form of free-standing and flexible character. Curcumin is a natural bioactive compound with poor water-solubility, however, the phase solubility test and dissolution/disintegration tests (water and artificial saliva) revealed that the water-solubility of curcumin was prominently improved by inclusion complexation with CyD. The antioxidant effect of curcumin in Curcumin/CyD webs was also enhanced due to higher solubility of curcumin by CyD inclusion complex. The results showed that HP-γ-CyD is significantly more effective than HP-ß-CyD in order to enhance the solubility and antioxidant property of curcumin in Curcumin/CyD webs.

Encapsulation and Stabilization of α-Lipoic Acid in Cyclodextrin Inclusion Complex Electrospun Nanofibers: Antioxidant and Fast-Dissolving α-Lipoic Acid/Cyclodextrin Nanofibrous Webs.

In this study, electrospinning of nanofibers from alpha-lipoic acid/cyclodextrin inclusion complex systems was successfully performed without having any polymeric matrix. Alpha-lipoic acid (α-LA) is a natural antioxidant compound which is widely used as a food supplement. However, it has limited water solubility and poor thermal and oxidative stability. Nevertheless, it is possible to enhance its water solubility and thermal stability by inclusion complexation with cyclodextrins. Here, hydroxypropyl-beta-cyclodextrin (HP-ß-CyD) and hydroxypropyl-gamma-cyclodextrin (HP-γ-CyD) were chosen as host molecules for forming inclusion complexation with α-LA. Accordingly, α-LA was inclusion complexed with HP-ß-CyD and HP-γ-CyD by using very high concentrated aqueous solutions of CyD (200%, w/v) having 1/1 and 2/1 molar ratio of α-LA/CyD. Except α-LA/HP-ß-CyD (1/1) solution, other α-LA/CyD solutions were turbid indicating the presence of some noncomplexed α-LA whereas α-LA/HP-ß-CyD (1/1) solution was very homogeneous signifying that α-LA was fully complexed with HP-ß-CyD. Even so, electrospinning was performed for all of the α-LA/HP-ß-CyD (1/1 and 2/1) and α-LA/HP-γ-CyD (1/1 and 2/1) aqueous solutions, and defect-free bead-less and uniform nanofibers were successfully obtained for all of the α-LA/CyD solutions. However, the electrospinning process for α-LA/CyD (1/1) systems was much more efficient than the α-LA/CyD (2/1) systems, and we were able to produce self-standing and flexible nanofibrous webs from α-LA/CyD (1/1) systems. α-LA was efficiently preserved during the electrospinning process of α-LA/CyD (1/1) systems and the resulting electrospun α-LA/HP-ß-CyD and α-LA/HP-γ-CyD nanofibers were produced with the molar ratios of ∼1/1 and ∼0.85/1 (α-LA/CyD), respectively. The better encapsulation efficiency of α-LA in α-LA/HP-ß-CyD nanofibers was due to higher solubility increase and higher binding strength between α-LA and HP-ß-CyD as revealed by the phase solubility test. α-LA was in the amorphous state in α-LA/CyD nanofibers and both α-LA/HP-ß-CyD and α-LA/HP-γ-CyD nanofibers were dissolved very quickly in water and also when they wetted with artificial saliva. Additionally, the antioxidant activity of pure α-LA and α-LA/CyD nanofibers was comparatively evaluated using ABTS radical cation assay. α-LA/CyD nanofibers have shown significantly higher antioxidant performance compared to pure α-LA owing to improved water solubility by CyD inclusion complexation. The thermal stability enhancement of α-LA in α-LA/CyD nanofibers was achieved compared to pure α-LA under heat treatment (100 °C for 24 h). These promising results support that antioxidant α-LA/CyD nanofibers may have potential applications as orally fast-dissolving food supplements.

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.

Antioxidant Vitamin E/Cyclodextrin Inclusion Complex Electrospun Nanofibers: Enhanced Water Solubility, Prolonged Shelf Life, and Photostability of Vitamin E.

Here, we demonstrated the electrospinning of polymer-free nanofibrous webs from inclusion complex (IC) between hydroxypropyl-ß-cyclodextrin (HPßCD) and Vitamin E (Vitamin E/HPßCD-IC NF). The inclusion complexation between HPßCD and Vitamin E was prepared by using two different molar ratios (Vitamin E/HPßCD; 1:2 and 1:1), which correspond to theoretical value of ∼13% (w/w) and 26% (w/w) loading of Vitamin E in the nanofiber (NF) matrix. After electrospinning and storage, a very high loading of Vitamin E (up to ∼11% w/w, with respect to fiber matrix) was preserved in Vitamin E/HPßCD-IC NF. Because of the cyclodextrin inclusion complexation, only a minimal weight loss (only ∼2% w/w) was observed. While pure Vitamin E is insoluble in water, Vitamin E/HPßCD-IC NF web has displayed fast-dissolving behavior. Because of the greatly enhanced water-solubility of Vitamin E, Vitamin E/HPßCD-IC NF web has shown effective antioxidant activity. Additionally, Vitamin E/HPßCD-IC NF web has provided enhanced photostability for the sensitive Vitamin E by the inclusion complexation in which Vitamin E/HPßCD-IC NF still kept its antioxidant activity even after exposure to UV-light. Moreover, a 3 year-old Vitamin E/HPßCD-IC NF sample has shown very similar antioxidant efficiency when compared with freshly prepared Vitamin E/HPßCD-IC NF indicating that long-term stability was achieved for Vitamin E in the CD-IC fiber matrix. In brief, our results suggested that polymer-free electrospun Vitamin E/HPßCD-IC nanofibrous webs could have potential applications in food, pharmaceuticals, and healthcare thanks to its efficient antioxidant activity along with enhanced water-solubility, prolonged shelf life, and high photostability of Vitamin E.

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.

Polymer-free nanofibers from vanillin/cyclodextrin inclusion complexes: high thermal stability, enhanced solubility and antioxidant property.

Vanillin/cyclodextrin inclusion complex nanofibers (vanillin/CD-IC NFs) were successfully obtained from three modified CD types (HPßCD, HPγCD and MßCD) in three different solvent systems (water, DMF and DMAc) via an electrospinning technique without using a carrier polymeric matrix. Vanillin/CD-IC NFs with uniform and bead-free fiber morphology were successfully produced and their free-standing nanofibrous webs were obtained. The polymer-free CD/vanillin-IC-NFs allow us to accomplish a much higher vanillin loading (∼12%, w/w) when compared to electrospun polymeric nanofibers containing CD/vanillin-IC (∼5%, w/w). Vanillin has a volatile nature yet, after electrospinning, a significant amount of vanillin was preserved due to complex formation depending on the CD types. Maximum preservation of vanillin was observed for vanillin/MßCD-IC NFs which is up to ∼85% w/w, besides, a considerable amount of vanillin (∼75% w/w) was also preserved for vanillin/HPßCD-IC NFs and vanillin/HPγCD-IC NFs. Phase solubility studies suggested a 1 : 1 molar complexation tendency between guest vanillin and host CD molecules. Molecular modelling studies and experimental findings revealed that vanillin : CD complexation was strongest for MßCD when compared to HPßCD and HPγCD in vanillin/CD-IC NFs. For vanillin/CD-IC NFs, water solubility and the antioxidant property of vanillin was improved significantly owing to inclusion complexation. In brief, polymer-free vanillin/CD-IC NFs are capable of incorporating a much higher loading of vanillin and effectively preserve volatile vanillin. Hence, encapsulation of volatile active agents such as flavor, fragrance and essential oils in electrospun polymer-free CD-IC NFs may have potential for food related applications by integrating the particularly large surface area of NFs with the non-toxic nature of CD and inclusion complexation benefits, such as high temperature stability, improved water solubility and an enhanced antioxidant property, etc.