Formulation of a fast-disintegrating drug delivery system from cyclodextrin/naproxen inclusion complex nanofibrous films.

Naproxen is a well-known non-steroidal anti-inflammatory drug (NSAID) that suffers from limited water solubility. The inclusion complexation with cyclodextrin (CD) can eliminate this drawback and the free-standing nanofibrous film (NF) generated from these inclusion complexes (ICs) can be a promising alternative formula as an orally disintegrating drug delivery system. For this, naproxen/CD IC NFs were generated using the highly water soluble hydroxypropylated derivative of ßCD (HPßCD) with two different molar ratios of 1/1 and 1/2 (drug/CD). The complexation energy calculated by the modeling study demonstrated a more favorable interaction between HPßCD and naproxen for the 1/2 molar ratio than 1/1. HPßCD/naproxen IC NFs were generated with loading concentrations of ∼7-11% and without using toxic chemicals. HPßCD/naproxen IC NFs indicated a faster and enhanced release profile in aqueous medium compared to pure naproxen owing to inclusion complexation. Moreover, rapid disintegration in less than a second was achieved in an artificial saliva environment.

Green Synthesis of Polycyclodextrin/Drug Inclusion Complex Nanofibrous Hydrogels: pH-Dependent Release of Acyclovir.

The development of an approach or a material for wound healing treatments has drawn a lot of attention for decades and has been an important portion of the research in the medical industry. Especially, there is growing interest and demand for the generation of wound care products using eco-friendly conditions. Electrospinning is one of these methods that enables the production of nanofibrous materials with attractive properties for wound healing under mild conditions and by using sustainable sources. In this study, starch-derived cyclodextrin (hydroxypropyl-ß-cyclodextrin (HPßCD)) was used both for forming an inclusion complex (IC) with acyclovir, a well-known antiviral drug, and for electrospinning of free-standing nanofibers. The nanofibers were produced in an aqueous system, without using a carrier polymer matrix and toxic solvent/chemical. The ultimate HPßCD/acyclovir-IC nanofibers were thermally cross-linked by using citric acid, listed in the generally regarded as safe (GRAS) category by the US Food and Drug Administration (FDA). The cross-linked HPßCD/acyclovir-IC nanofibers displayed stability in aqueous medium. The hydrogel-forming feature of nanofibers was confirmed with their high swelling profile in water in the range of ∼610-810%. Cellulose acetate (CA)/acyclovir nanofibers were also produced as the control sample. Due to inclusion complexation with HPßCD, the solubility of acyclovir was improved, so cross-linked HPßCD/acyclovir-IC nanofibrous hydrogels displayed a better release performance compared to CA/acyclovir nanofibers. Here, a pH-dependent release profile was obtained (pH 5.4 and pH 7.4) besides their attractive swelling features. Therefore, the cross-linked HPßCD/acyclovir-IC nanofibrous hydrogel can be a promising candidate as a wound healing dressing for the administration of antiviral drugs by holding the unique properties of CD and electrospun nanofibers.

Fast-Disintegrating Nanofibrous Web of Pullulan/Griseofulvin-Cyclodextrin Inclusion Complexes.

Griseofulvin (GSF) is one of the most widely used antifungal suffering from low water solubility and limited bioavailability. Here, cyclodextrin (CD) derivatives of hydroxypropyl-beta-CD (HPßCD) known for its high-water solubility were used to form inclusion complexes (ICs) with GSF. Here, the molecular modeling study revealed the more efficient complex formation with 1:2 (guest:CD) stoichiometry, so ICs of GSF-HPßCD were prepared using a 1:2 molar ratio (GSF:HPßCD) and then mixed with pullulan (PULL) to generate nanofibers (NFs) using the electrospinning technique. PULL is a nontoxic water-soluble biopolymer and the ultimate PULL/GSF-HPßCD-IC NF was obtained with a defect-free fiber morphology having 805 ± 180 nm average diameter. The self-standing and flexible PULL/GSF-HPßCD-IC NF was achieved to be produced with a loading efficiency of ∼98% corresponding to ∼6.4% (w/w) of drug content. In comparison, the control sample of PULL/GSF NF was formed with a lower loading efficiency value of ∼72% which equals to ∼4.7% (w/w) of GSF content. Additionally, PULL/GSF-HPßCD-IC NF provided an enhanced aqueous solubility for GSF compared to PULL/GSF NF so a faster release profile with ∼2.5 times higher released amount was obtained due to inclusion complexation between GSF and HPßCD within the nanofibrous web. On the other hand, both nanofibrous webs rapidly disintegrated (∼2 s) in the artificial saliva medium that mimics the oral cavity environment. Briefly, PULL/GSF-HPßCD-IC NF can be a promising dosage formulation as a fast-disintegrating delivery system for antifungal oral administration owing to the improved physicochemical properties of GSF.

Ondansetron/Cyclodextrin inclusion complex nanofibrous webs for potential orally fast-disintegrating antiemetic drug delivery.

Ondansetron (ODS) is an effective antiemetic drug which suffers from limited solubility and bioavailability during oral administration due to first-pass metabolism. However, these limitations can be mitigated through inclusion complexation with cyclodextrins (CDs). In this study, we have reported the electrospinning of polymer-free, free-standing ODS/CD nanofibrous webs (NW), a promising approach for developing a fast-disintegrating delivery system of an antiemetic drug molecule. Highly water soluble hydroxypropyl-beta-cyclodextrins (HPßCD) were used as both complexation agent and electrospinning matrix. The computational study revealed that the 1/2 (drug/CD) stoichiometry was more favorable compared to 1/1. The ODS/HPßCD NW was obtained with higher loading efficiency (∼96 %) compared to the control sample of ODS/polyvinyl alcohol (PVA) NW (∼80 %). The amorphous distribution of ODS raised by complexation and the highly water-soluble nature of HPßCD resulted into faster and better release profile and quite faster disintegration property (∼2 s) in artificial saliva than polymeric ODS/PVA NW. Here, ODS/HPßCD NW was generated in the absence of a toxic solvent or chemical to enable the drug loading in an amorphous state. From all reasons above, ODS/HPßCD NW might be a promising alternative to the polymeric based systems for the purpose of fast-disintegrating oral drug delivery.

Antibacterial nanofibers of pullulan/tetracycline-cyclodextrin inclusion complexes for Fast-Disintegrating oral drug delivery.

Tetracycline is a widely used antibiotic suffering from poor water solubility and low bioavailability. Here, hydroxypropyl-beta-cyclodextrin (HPßCD) was used to form inclusion complexes (IC) of tetracycline with 2:1 M ratio (CD:drug). Then, tetracycline-HPßCD-IC was mixed with pullulan- a non-toxic, water-soluble biopolymer - to form nanofibrous webs via electrospinning. The electrospinning of pullulan/tetracycline-HPßCD-IC was yielded into defect-free nanofibers collected in the form of a self-standing and flexible material with the loading capacity of âˆ¼ 7.7 % (w/w). Pullulan/tetracycline nanofibers was also generated as control sample having the same drug loading. Tetracycline was found in the amorphous state in case of pullulan/tetracycline-HPßCD nanofibers due to inclusion complexation. Through inclusion complexation with HPßCD, enhanced aqueous solubility and faster release profile were provided for pullulan/tetracycline-HPßCD-IC nanofibers compared to pullulan/tetracycline one. Additionally, pullulan/tetracycline-HPßCD-IC nanofibers readily disintegrated when wetted with artificial saliva while pullulan/tetracycline nanofibers were not completely absorbed by the same simulate environment. Electrospun nanofibers showed promising antibacterial activity against both gram-positive and gram-negative bacteria. Briefly, our findings indicated that pullulan/tetracycline-HPßCD-IC nanofibers could be an attractive material as orally fast disintegrating drug delivery system for the desired antibiotic treatment thanks to its promising physicochemical and antibacterial properties.

Orally Fast Disintegrating Cyclodextrin/Prednisolone Inclusion-Complex Nanofibrous Webs for Potential Steroid Medications.

Prednisolone is a widely used immunosuppressive and anti-inflammatory drug type that suffers from low aqueous solubility and bioavailability. Due to the inclusion complexation with cyclodextrins (CDs), prednisolone's drawbacks that hinder its potential during the administration can be eliminated effectively. Here, we have early shown the electrospinning of free-standing nanofibrous webs of CD/prednisolone inclusion complexes (ICs) in the absence of a polymer matrix. In this study, hydroxypropyl-beta-CD (HPßCD) has been used to form ICs with prednisolone and generate nanofibrous webs with a drug loading capacity of ∼10% (w/w). Pullulan/prednisolone nanofibrous webs have been also fabricated as a control sample having the same drug loading (∼10%, w/w). It has been demonstrated that prednisolone has been found in an amorphous state in the HPßCD/prednisolone nanofibrous web due to inclusion complexation, while it has retained its crystal structure in the pullulan/prednisolone nanofibrous web. Therefore, the HPßCD/prednisolone IC nanofibrous web has shown a faster and enhanced release profile and superior disintegration feature in artificial saliva than the pullulan/prednisolone nanofibrous web. The complexation energy calculated using ab initio modeling displayed a more favorable interaction between HPßCD and prednisolone in the case of a molar ratio of 2:1 than 1:1 (CD: drug). Here, the HPßCD/prednisolone IC nanofibrous web has been developed without using a toxic component or solvent to dissolve drug molecules and boost drug loading in amorphous nature. The investigation of IC nanofibrous webs has been conducted to formulate a promising alternative to the orally disintegrating tablet formulation of prednisolone in the market. The nanofibrous structure and the improved physicochemical properties of prednisolone arising with the complexation might ensure a faster disintegration and onset of action against commercially available and orally disintegrating delivery systems during the desired treatment.

Single nozzle electrospinning promoted hierarchical shell wall structured zinc oxide hollow tubes for water remediation.

HYPOTHESIS: Electrospun metal oxide hollow tubes are of great interest owing to their unique structural advantages compared to solid nanofibers. Although intensive research on preparation of hollow tubes have been devoted, formation of hierarchical shells remains a significant challenge. EXPERIMENTS: Herein, we demonstrate the fabrication of highly uniform, reproducible and industrially feasible ZnO hollow tubes (ZHT) with two-level hierarchical shells via a simple and versatile single-nozzle electrospinning strategy coupled with subsequent controlled thermal treatment. FINDINGS: The morphological investigation reveals that the hollow tubes built from nanostructures which has unique surface structure on their wall. The mechanism by which the composite fibers transferred to hollow tubes is primarily based on the evaporation rate of the polymeric template. Notably, tuning the heating rate from 5 °C to 50 °C/min possess adverse effect on formation of hollow tubes, thus subsequently produced ZnO nanoplates (ZNP). The comparative photocatalytic analysis emphasized that ZHT shows higher photocatalytic activity than ZNP. This finding has made an evident that the inherent abundant defects in the electrospun derived nanostructures are not only sufficient for improving the photocatalytic activity. Studies on bacterial growth inhibition showcased a superior bactericidal effect against Staphylococcus aureus and Escherichia coli implying its potentiality for disinfecting the bacteria from water.

Electrospun formulation of acyclovir/cyclodextrin nanofibers for fast-dissolving antiviral drug delivery.

Acyclovir is an effective antiviral drug which suffers from limited water solubility and low bioavailability. However, it is possible to eliminate these limitations by forming inclusion complexes with cyclodextrins. In this study, we have reported the electrospinning of polymer-free and free-standing acyclovir/cyclodextrin nanofibers for the first time. This is a promising approach for developing a fast-dissolving delivery system of an antiviral drug molecule. Here, hydroxypropyl-beta-cyclodextrin (HP-ßCD) was used as both complexation agent and electrospinning matrix. The acyclovir/HP-ßCD system was prepared by incorporating ~7% (w/w) of acyclovir into the highly concentrated aqueous solution of HP-ßCD (180%, w/v). The control sample of acyclovir/polyvinylpyrrolidone (PVP) nanofiber were also generated using ethanol/water (3/1, v/v) solvent system and the same initial acyclovir (7%, w/w) content. Due to the inclusion complexation, acyclovir/HP-ßCD nanofibers provided better encapsulation and so loading efficiency. The loading efficiency of acyclovir/HP-ßCD nanofibers was determined as ~98%, while it was ~66% for acyclovir/PVP nanofibers. It was found that acyclovir/HP-ßCD nanofibers contained some crystalline form of acyclovir. Even so, it showed faster dissolving/release and faster disintegration profiles compared to acyclovir/PVP nanofibers which had higher amount of crystalline acyclovir. The inclusion complexation property and high water solubility of HP-ßCD (> 2000 mg/mL) ensured the fast-dissolving property of acyclovir/HP-ßCD nanofibers. Briefly, acyclovir/HP-ßCD nanofibers are quite promising alternative to the polymeric based system for the purpose of fast-dissolving oral drug delivery. The enhanced physicochemical properties of drug molecules and the use of water during whole process can make drug/cyclodextrin nanofibers a favorable dosage formulation for the desired treatments.

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.

Progress in the design and development of "fast-dissolving" electrospun nanofibers based drug delivery systems - A systematic review.

Electrospinning has emerged as most viable approach for the fabrication of nanofibers with several beneficial features that are essential to various applications ranging from environment to biomedicine. The electrospun nanofiber based drug delivery systems have shown tremendous advancements over the controlled and sustained release complemented from their high surface area, tunable porosity, mechanical endurance, offer compatible environment for drug encapsulation, biocompatibility, high drug loading and tailorable release characteristics. The dosage formulation of poorly water-soluble drugs often faces several challenges including complete dissolution with maximum therapeutic efficiency over a short period of time especially through oral administration. In this context, challenges associated with the dosage formulation of poorly-water soluble drugs can be addressed through combining the beneficial features of electrospun nanofibers. This review describes major developments progressed in the preparation of electrospun nanofibers based "fast dissolving" drug delivery systems by employing variety of polymers, drug molecules and encapsulation approaches with primary focus on oral delivery. Furthermore, the review also highlights current scientific challenges and provide an outlook with regard to future prospectus.

Development of ferulic acid/cyclodextrin inclusion complex nanofibers for fast-dissolving drug delivery system.

Production of electrospun nanofibrous mats of cyclodextrin inclusion complexes with the incorporation of drug molecules would enable promising designing of fast dissolving delivery systems (FDDS) for oral treatments. Here, the single-step electrospinning technique has been applied to prepare cyclodextrin inclusion complex nanofibrous mats (CD-IC NM) of ferulic acid from complete aqueous systems without using any polymeric matrix. The free-standing ferulic acid/CD-IC NM have been electrospun from two different modified cyclodextrin derivatives of hydroxypropyl-beta-cyclodextrin (HP-ß-CD) and hydroxypropyl-gamma-cyclodextrin (HP-γ-CD). The initial content of ferulic acid (1/1 ferulic acid/CD (molar ratio) and ~11% (w/w)) has been protected in case of both ferulic acid/CD-IC NM and so the electrospun nanofibrous mats have been fabricated by the ~100% loading efficiency. It has been detected from the in vitro release and disintegration tests that, the amorphous state of ferulic acid based on inclusion complex formation, and the highly porous feature and high surface area of nanofibrous mats have ensured the fast dissolution/release of ferulic acid and disintegration of nanofibrous mats into the liquid medium and artificial saliva. Herein, HP-γ-CD has formed inclusion complexes with ferulic acid more favorably than HP-ß-CD and this has leaded to the existence of some un-complexed ferulic acid crystals in ferulic acid/HP-ß-CD-IC NM while, ferulic acid has been completely complexed and is in amorphous state in ferulic acid/HP-γ-CD-IC NM. Furthermore, the thermal stability of ferulic acid has been enhanced as an inclusion complexation aid observed by the shift of thermal degradation temperature of ferulic acid from the range of ~120-200 °C to ~140-280 °C.

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.

Hydrocortisone/cyclodextrin complex electrospun nanofibers for a fast-dissolving oral drug delivery system.

The electrospinning of hydrocortisone/cyclodextrin complex nanofibers was performed in order to develop a fast-dissolving oral drug delivery system. Hydrocortisone is a water-insoluble hydrophobic drug, yet, the water solubility of hydrocortisone was significantly enhanced by inclusion complexation with hydroxypropyl-beta-cyclodextrin (HP-ß-CyD). In this study, hydrocortisone/HP-ß-CyD complexes were prepared in aqueous solutions having molar ratios of 1/1, 1/1.5 and 1/2 (hydrocortisone/HP-ß-CyD). Highly concentrated aqueous solutions of HP-ß-CyD (180%, w/v) were used for hydrocortisone/HP-ß-CyD systems (1/1, 1/1.5 and 1/2) in order to perform electrospinning without the use of an additional polymer matrix. The turbidity of hydrocortisone/HP-ß-CyD (1/1 and 1/1.5) aqueous solutions indicated the presence of some uncomplexed crystals of hydrocortisone whereas the aqueous solution of hydrocortisone/HP-ß-CyD (1/2) was homogeneous indicating that hydrocortisone becomes totally water-soluble by inclusion complexation with HP-ß-CyD. Nonetheless, the electrospinning of hydrocortisone/HP-ß-CyD systems (1/1, 1/1.5 and 1/2) successfully yielded defect-free uniform nanofibrous structures. Moreover, the electrospinning process was quite efficient that hydrocortisone was completely preserved without any loss yielding hydrocortisone/HP-ß-CyD nanofibers having the initial molar ratios (1/1, 1/1.5 and 1/2). The structural and thermal characterization of the hydrocortisone/HP-ß-CyD nanofibers revealed that hydrocortisone was totally inclusion complexed with HP-ß-CyD and was in the amorphous state in hydrocortisone/HP-ß-CyD (1/2) nanofibers whereas some uncomplexed crystalline hydrocortisone was present in hydrocortisone/HP-ß-CyD (1/1 and 1/1.5) nanofibers. Nevertheless, hydrocortisone/HP-ß-CyD (1/1, 1/1.5 and 1/2) complex aqueous systems were electrospun in the form of nanofibrous webs having a free-standing and flexible nature. The hydrocortisone/HP-ß-CyD (1/1, 1/1.5 and 1/2) nanofibrous webs have shown fast-dissolving behavior in water or when they were in contact with artificial saliva. Yet, the hydrocortisone/HP-ß-CyD (1/2) nanofibrous web dissolved more quickly than the hydrocortisone/HP-ß-CyD (1/1 and 1/1.5) nanofibrous webs due to the full inclusion complexation and the amorphous state of hydrocortisone in this sample. In short, the results suggest that polymer-free electrospun nanofibrous webs produced from hydrocortisone/HP-ß-CyD could be quite applicable for fast-dissolving oral drug delivery systems.

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.

Metronidazole/Hydroxypropyl-ß-Cyclodextrin inclusion complex nanofibrous webs as fast-dissolving oral drug delivery system.

In this study, Metronidazole/Hydroxypropyl-ß-Cyclodextrin (HP-ß-CyD) inclusion complex nanofibrous webs were produced via electrospinning for the purpose of fast-dissolving oral drug delivery. The Metronidazole/HP-ß-CyD inclusion complex aqueous solutions having two different molar ratio of Metronidazole/HP-ß-CyD (1/1 and 1/2) were prepared by using very high concentration of HP-ß-CyD (200%, w/v) in order to achieve polymer-free electrospinning of Metronidazole/HP-ß-CyD nanofibers (NF). Metronidazole was totally encapsulated and preserved without any loss during the electrospinning process in which both systems yielded Metronidazole/HP-ß-CyD NF having the same initial molar ratio of 1/1 and 1/2. The electrospinning of both Metronidazole/HP-ß-CyD (1/1 and 1/2) aqueous solutions yielded uniform and bead-less fiber morphology having ~190 nm average fiber diameter. Both Metronidazole/HP-ß-CyD NF (1/1 and 1/2) samples were in the form of nanofibrous webs with free-standing and flexible character. The structural and thermal characterizations of Metronidazole/HP-ß-CyD NF (1/1 and 1/2) proved that Metronidazole was in the inclusion complex state with HP-ß-CyD in these nanofibrous webs. Metronidazole is an antibiotic which is poorly water-soluble drug, but the phase solubility and dissolution tests revealed that the water-solubility of Metronidazole was significantly enhanced by HP-ß-CyD inclusion complexation. In addition, Metronidazole/HP-ß-CyD (1/1 and 1/2) nanofibrous webs have shown very fast-dissolving behavior when placed in water or contacted to artificial saliva suggesting that such Metronidazole/HP-ß-CyD nanofibrous webs can be suitable for fast-dissolving oral drug delivery.

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.

Fast Dissolving Oral Drug Delivery System Based on Electrospun Nanofibrous Webs of Cyclodextrin/Ibuprofen Inclusion Complex Nanofibers.

In this study, the polymer-free electrospinning was performed in order to produce cyclodextrin/ibuprofen inclusion complex nanofibers, which could have potential as the fast dissolving oral drug delivery system. Ibuprofen is a poorly water-soluble nonsteroidal anti-inflammatory drug; however, the water solubility of ibuprofen can be significantly enhanced by inclusion complexation with cyclodextrins. Here, hydroxypropyl-beta-cyclodextrin (HPßCyD) was chosen both as a nanofiber matrix and host molecule for inclusion complexation in order to enhance water solubility and fast dissolution of ibuprofen. Ibuprofen was inclusion-complexed with HPßCyD in highly concentrated aqueous solutions of HPßCyD (200%, w/v) having two different molar ratios: 1:1 and 2:1 (HPßCyD/ibuprofen). The HPßCyD/ibuprofen-IC (1:1) aqueous solution was turbid having some undissolved/uncomplexed ibuprofen, whereas HPßCyD/ibuprofen-IC (2:1) aqueous solution was homogeneous and clear, indicating that ibuprofen was totally complexed with HPßCyD and becomes water soluble. Then, both HPßCyD/ibuprofen-IC solutions (1:1 and 2:1) were electrospun into bead-free and uniform nanofibers having ∼200 nm fiber diameter. The electrospun HPßCyD/ibuprofen-IC nanofibers were obtained as nanofibrous webs having self-standing and flexible character, which is appropriate for fast dissolving oral drug delivery systems. Ibuprofen was completely preserved during the electrospinning process, and the resulting electrospun HPßCyD/ibuprofen-IC nanofibers were produced without any loss of ibuprofen by preserving the initial molar ratio of 1:1 and 2:1 (HPßCyD/ibuprofen). X-ray diffraction and differential scanning calorimetry measurements indicated the presence of some crystalline ibuprofen in HPßCyD/ibuprofen-IC (1:1) nanofibers, whereas ibuprofen was totally in the amorphous state in HPßCyD/ibuprofen-IC (2:1) nanofibers. Nonetheless, both HPßCyD/ibuprofen-IC (1:1 and 2:1) nanofibrous webs have shown very fast dissolving character when contacted with water or when wetted with artificial saliva. In brief, our results revealed that electrospun HPßCyD/ibuprofen-IC nanofibrous webs have potential as fast dissolving oral drug delivery systems.

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.