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The conversion of CaSO₄·0.5H₂O to CaSO₄·2H₂O (gypsum) is of great importance industrially, being the reaction behind plasterboard production and the setting of medical plasters. This hydration process is inherently slow, and to ensure that it occurs on a practical timescale, “seeds” of gypsum are typically added to accelerate the reaction. The seeds used in industry are mostly produced by milling quarried gypsum, resulting in huge variations in their accelerant properties between batches. Here, we develop a bottom-up process to prepare gypsum seeds with a tightly defined morphology, using starch as a templating agent during precipitation from water/ethanol mixtures. When the seeds thereby generated are dried, they tend to aggregate, which results in diminished accelerant properties. The hydration (or setting) time can be markedly reduced if these aggregates are broken up and suspended in a liquid medium. This indicates that directly adding the suspension reaction product to an industrial production line could be a powerful way to accelerate the setting reaction. However, the use of ethanol in the seed synthesis precludes this (because the ethanol would halt the setting reaction). Therefore, a direct one-step process involving evaporation of ethanol was developed to produce gypsum seeds in a water suspension with no ethanol present. The resultant “liquid seeds” are highly potent in accelerating the hydration process of CaSO₄·0.5H₂O to CaSO₄·2H₂O, resulting in shorter setting times than a commercial standard gypsum accelerant.

Given the increasing interest in the use of peptide- and protein-based agents in therapeutic strategies, it is fundamental to develop delivery systems capable of preserving the biological activity of these molecules upon administration, and which can provide tuneable release profiles. Electrohydrodynamic (EHD) techniques, encompassing electrospinning and electrospraying, allow the generation of fibres and particles with high surface area-to-volume ratios, versatile architectures, and highly controllable release profiles. This review is focused on exploring the potential of different EHD methods (including blend, emulsion, and co /multi-axial electrospinning and electrospraying) for the development of peptide and protein delivery systems. An overview of the principles of each technique is first presented, followed by a survey of the literature on the encapsulation of enzymes, growth factors, antibodies, hormones, and vaccine antigens using EHD approaches. The possibility for localised delivery using stimuli-responsive systems is also explored. Finally, the advantages and challenges with each EHD method are summarised, and the necessary steps for clinical translation and scaled-up production of electrospun and electrosprayed protein delivery systems are discussed.

A major reduction in energy consumption and the costs of catalysts will be required in future chemical manufacturing processes. To reach this goal, the transitional metal oxides (TMOs) as photocatalysts under solar energy have been widely studied. Nb₂O5, as a promising photocatalyst, has attracted increasing attention owing to their unique properties. However, the intrinsic large bandgap of Nb₂O5 hinder its potential applications in a variety of fields. Herein, we report an effective and simple strategy to synthesize black mesoporous Nb₂O5-x nanorods (BMNb) with abundant oxygen vacancies. The formation of oxygen vacancy reduces the bandgap of Nb₂O5 which extend the photoresponse from the ultraviolet to the visible and infrared light regions. In addition, The mesoporous structure of BMNb lead to a higher surface area than the as-prepared Nb₂O5 precursor (36.24 m²/g cf 8.69 m²/g). Benefitting from coordinated regulation of structure and composition, the BMNb exhibits better photocatalytic performance than Nb₂O5 in aerobic oxidative coupling of amines to imines under visible light irradiation at room temperature. The yield of BMNb for benzylamine oxidation increases by 63% over the Nb₂O5. This work could open new perspectives to design TMOs with enhanced photocatalytic properties.

Abstract We report in this work coaxial electrospun fibers with potential applications in the treatment of Parkinson’s disease. The fibers comprise a fixed dose combination (FDC) containing the active ingredients levodopa and carbidopa, loaded in a fast dissolving polyvinylpyrrolidone (PVP) shell and an insoluble but swellable Eudragit® RLPO core. Under appropriate processing conditions we are able to prepare fibers with distinct core/shell architectures and diameters of approximately 400 nm. X-ray diffraction and differential scanning calorimetry analyses revealed that the drugs are dispersed on the molecular level within the polymer carriers, and IR spectroscopy indicated the presence of intermolecular interactions. At pH 1, the composite fibers yields extended release over more than 8 h, with an initial loading dose being freed from the PVP shell and then a sustained release phase following from the insoluble core. This is markedly extended over the release period of the commercial FDC product, and thus the fibers generated here have the potential to be used to reduce the required dosing frequency. Graphic Abstract

Transdermal delivery of biological therapeutics is emerging as a potent alternative to intravenous or subcutaneous injections. The latter come with major challenges including patient discomfort, the necessity for trained personnel, specialized sharps disposal, and risk of infection. Microneedle (MN) technology circumvents many of the abovementioned challenges, delivering biological material directly into the skin and allowing sustained release of the active ingredient both in animal models and in humans. This study describes the use of electrohydrodynamic atomization (EHDA) to coat ovalbumin (OVA)-encapsulated PLGA nanoparticles onto hydrogel-forming MN arrays. The particles showed extended release of OVA over ca. 28 days. Microscopic analysis demonstrated that EHDA could generate a uniform particle coating on the MNs, with 30% coating efficiency. Furthermore, the coated MN array manifested similar mechanical characteristics and insertion properties to the uncoated system, suggesting the coating should have no detrimental effects on the application of the MNs. The coated MNs resulted in no significance increase in anti-OVA specific IgG titres in C57BL/6 mice in vivo as compared to the untreated mice (paired t-test, p >0.05) indicating that the formulations are non-immunogenic. The approach of using EHDA to coat a MN array thus appears to have potential as a novel non-invasive protein delivery strategy.

Electrospinning is an inexpensive and powerful method that employs a polymer solution and strong electric field to produce nanofibers. These can be applied in diverse biological and medical applications. Due to their large surface area, controllable surface functionalization and properties, and typically high biocompatibility electrospun nanofibers are recognized as promising materials for the manufacturing of drug delivery systems. Electrospinning offers the potential to formulate poorly soluble drugs as amorphous solid dispersions to improve solubility, bioavailability and targeting of drug release. It is also a successful strategy for the encapsulation of nutraceuticals. This review aims to briefly discuss the concept of electrospinning and recent progress in manufacturing electrospun drug delivery systems. It will further consider in detail the encapsulation of nutraceuticals, particularly probiotics.

In this study, the polymorphic transitions of mefenamic acid (MA) were studied by synchrotron X-ray powder diffraction combined with differential scanning calorimetry (XRD-DSC). The initial material was found to be phase-pure form I which, when heated, produces two endotherms that can be observed by DSC at 162.72 and 219.55°C. The former was found to correspond to a solid–solid enantiotropic transition from form I to a mixture of forms II and III. The latter is the melting point of form II. As form I is heated, significantly greater unit-cell expansion is seen in the a direction than in b and c, which can be explained by the stronger intermolecular interactions in the bc plane. Refinements of the reported MA structures against the patterns collected during heating revealed that at 175°C there exists a mixture of forms I, II and III, whereas only forms II and III remain at 205°C. However, reflections are observed at both temperatures which cannot be fitted with the known forms of MA. It is hypothesized that a new form of MA is produced upon heating. The stability of MA after the enantiotropic transition temperature is II > III > I, which differs from the previously reported II > I > III.

In this paper, a modified coaxial electrospraying process was explored for the generation of novel nanoscale composite materials. A solution comprising 5% (w/v) of the model drug helicid and 10% (w/v) polyvinylpyrrolidone (PVP) K10 in a mixture of N,N-dimethylacetamide and ethanol (4:6, v:v) was employed as the shell working liquid. This could not be processed into a solid product when processed by single-fluid electrospraying. However, when undertaking co-axial electrospraying with a core shellac solution (40% w/v in ethanol) solid particles were obtained. An extremely thin nanocoating layer of drug-polymer composite with an estimated thickness of 7 nm was deposited on a shellac core. X-ray diffraction and infrared spectroscopy demonstrated that the drug was converted into an amorphous nanocomposite with the PVP in the shell layer, losing its original crystalline state. In vitro dissolution tests revealed that all the helicid loading could be released within one minute, suggesting the particles have potential applications to deliver very rapid therapeutic effects. Mechanisms are proposed underlying the formation and functional performance of the materials.

Olanzapine is a polymorphic drug molecule that has been extensively studied, with over 60 structures reported in the Cambridge Structural Database. All anhydrous and solvated forms of olanzapine known to date contain the SC0 dimer packing motif. In this study, a new screening approach was adopted involving heat-induced forced crystallization from a polymer-based molecular dispersion of olanzapine. Simultaneous differential scanning calorimetry–powder X-ray diffraction was used to heat the amorphous dispersion and to identify a novel physical form from diffraction and heat flow data. Comparison of the diffraction data with those from a computed crystal energy landscape allowed the crystal structure to be determined. The result was the discovery of a new polymorph, form IV, which does not use the SC0 motif. Hence, while dimer formation is the dominant process that defines crystal packing for olanzapine formed from solution, it seems that molecularly dispersing the drug in a polymeric matrix permits crystall...

The ability to accurately control a material’s structure, and in turn its functional performance, is of crucial importance for potential applications. In this study, a new modified triaxial electrospinning process was successfully developed to allow us to precisely tune drug release from nanoscale formulations. In this process, we used two un-electrospinnable liquids as the outer and middle working fluids, with only the core solution being individually electrospinnable into fibers. The outer liquid comprised a mixture of solvents, while the middle fluid was a dilute solution of cellulose acetate (CA). The core fluid was an electrospinnable co-dissolving solution of ferulic acid (FA) and gliadin. By processing these in triaxial electrospinning, we were able to create FA-gliadin fibers coated with a thin but even and continuous coating of CA. The thickness of the CA coating could be precisely varied by adjusting the flow rate of the middle working fluid. The resultant nanofibers have linear and cylindrical morphologies with clear core-shell structures. X-ray diffraction and IR spectroscopy data verified that the fibers comprised amorphous solid dispersions, with intermolecular interactions existing between FA and gliadin. The CA coating eliminated the initial burst release seen with uncoated FA-gliadin fibers, and also led to close to zero-order release profiles which could be incrementally adjusted by varying the thickness of the coating. New process-nanostructure-performance relationships are therefore revealed, and the advanced triaxial electrospinning approach reported in this work has great potential for developing new kinds of functional nanomaterials.

The development of oral dosage forms for poorly water-soluble active pharmaceutical ingredients (APIs) is a persistent challenge. A range of methods has been explored to address this issue, and amorphous solid dispersions (ASDs) have received increasing attention. ASDs are typically prepared by starting with a liquid precursor (a solution or melt) and applying energy for solidification. Many techniques can be used, with the emergence of electrospinning as a potent option in recent years. This method uses electrical energy to induce changes from liquid to solid. Through the direct applications of electrical energy, electrospinning can generate nanofiber-based ASDs from drug-loaded solutions, melts and melt-solutions. The technique can also be combined with other approaches using the application of mechanical, thermal or other energy sources. Electrospinning has numerous advantages over other approaches to produce ASDs. These advantages include extremely rapid drying speeds, ease of implentation, compatibility with a wide range of active ingredients (including those which are thermally labile), and the generation of products with large surface areas and high porosity. Furthermore, this technique exhibits the potential to create so-called 'fifth-generation' ASDs with nanostructured architectures, such as core/shell or Janus systems and their combinations. These advanced systems can improve dissolution behaviour and provide programmable drug release profiles. Additionally, the fiber components and their spatial distributions can be precisely controlled. Electrospun fiber-based ASDs can maintain an incorporated active ingredient in the amorphous physical form for prolonged periods of time because of their homogeneous drug distribution within the polymer matrix (typically they comprise solid solutions), and ability to inhibit molecular motion. These ASDs can be utilised to generate oral dosage forms for poorly water-soluble drugs, resulting in linear or multiple-phase release of one or more APIs. Electrospun ASDs can also be exploited as templates for manipulating molecular self-assembly, offering a bridge between ASDs and other types of dosage forms. This review addresses the development, advantages and pharmaceutical applications of electrospinning for producing polymeric ASDs. Material preparation and analysis procedures are considered. The mechanisms through which performance has been improved are also discussed.

In article number 2000272 by Ruizheng Liang, Xisheng Weng, Min Wei, and co‐workers, CoFeMn dichalcogenide nanosheets with ultrahigh photothermal conversion efficiency (η = 89.0%) were prepared via facile vulcanization of a lamellar CoFeMn‐layered double hydroxide precursor, which provides a new approach for the synthesis of high‐quality multicomponent TMD nanosheets with precise process control, mass production, and excellent photoacoustic imaging and synergistic photothermal/chemodynamic therapy performance. [Image: see text]

Amorphous solid dispersions (ASDs) of class II and IV biopharmaceutics classification system drugs in water-miscible polymers are a well-recognized means of enhancing dissolution, while such dispersions in hydrophobic polymers form the basis of micro- and nanoparticulate technologies. However, drug recrystallization presents significant problems for product development, and the mechanisms and pathways involved are poorly understood. Here, we outline the use of combined differential scanning calorimetry (DSC)-synchrotron X-ray diffraction to monitor the sequential appearance of polymorphs of olanzapine (OLZ) when dispersed in a range of polymers. In a recent study (Cryst. Growth Des. 2019, 19, 2751-2757), we reported a new polymorph (form IV) of OLZ which crystallized from a spray-dried dispersion of OLZ in polyvinylpyrrolidone. Here, we extend our earlier study to explore OLZ dispersions in poly(lactide-co-glycolide) (PLGA), polylactide (PLA), and hydroxypropyl methyl cellulose acetate succinate (HPMCAS), with a view to identifying the sequence of form generation on heating each dispersion. While spray-dried OLZ results in the formation of crystalline form I, the spray-dried material with HPMCAS comprises an ASD, and forms I and IV are generated upon heating. PLGA and PLA result in a product which contains both amorphous OLZ and the dichloromethane solvate; upon heating, the amorphous material converts to forms I, II, and IV and the solvate to forms I and II. Our data show that it is possible to quantitatively assess not only the polymorph generation sequence but also the relative proportions as a function of temperature. Of particular note is that the sequence of form generation is significantly more complex than may be indicated by DSC data alone, with coincident generation of different polymorphs and complex interconversions as the material is heated. We argue that this may have implications not only for the mechanistic understanding of polymorph generation but also as an aid to identifying the range of polymorphic forms that may be produced by a single-drug molecule.

In nature, the combination of composition, structure, and shape determines the matter's functional performance to a large extent. Inspired by which, two electrospun Janus nanofiber formulations were created using side-by-side electrospinning in this work. Tamoxifen citrate (TAM) was used as a model drug and ethyl cellulose (EC) and polyvinylpyrrolidone K60 (PVP) as the polymer carrier matrices. The fibers have linear cylindrical morphologies and distinct Janus structures by scanning electron microscopy. One side of the fibers took a round shape, while the other was crescent-shaped. The drug was present in both polymer matrices in the form of amorphous solid dispersions, owing to strong intermolecular interactions between drug and polymer. In vitro dissolution tests demonstrated that both sets of fibers could provide biphasic drug release due to the difference in solubility of PVP and EC. The different shape of TAM-EC and TAM-PVP side of the Janus structure resulted in a considerable variation in the drug release profiles. The Janus structure with crescent TAM-PVP side and round TAM-EC side gave a more rapid burst release in the first phase of release, and slower sustained release in the second phase. This work thus reports a new strategy for systematically developing advanced functional nanomaterials based on both shape- and structure-performance relationships.

Although electrospun nanofibers are expanding their potential commercial applications in various fields, the issue of energy savings, which are important for cost reduction and technological feasibility, has received little attention to date. In this study, a concentric spinneret with a solid Teflon-core rod was developed to implement an energy-saving electrospinning process. Ketoprofen and polyvinylpyrrolidone (PVP) were used as a model of a poorly water-soluble drug and a filament-forming matrix, respectively, to obtain nanofibrous films via traditional tube-based electrospinning and the proposed solid rod-based electrospinning method. The functional performances of the films were compared through in vitro drug dissolution experiments and ex vivo sublingual drug permeation tests. Results demonstrated that both types of nanofibrous films do not significantly differ in terms of medical applications. However, the new process required only 53.9% of the energy consumed by the traditional method. This achievement was realized by the introduction of several engineering improvements based on applied surface modifications, such as a less energy dispersive air-epoxy resin surface of the spinneret, a free liquid guiding without backward capillary force of the Teflon-core rod, and a smaller fluid&ndash, Teflon adhesive force. Other non-conductive materials could be explored to develop new spinnerets offering good engineering control and energy savings to obtain low-cost electrospun polymeric nanofibers.

In this work, the non-steroidal anti-inflammatory drugs ibuprofen (ibu) and ketoprofen (ket), both poorly soluble in water, were first intercalated into layered double hydroxide (LDH) nanoparticles. The drug–LDH composites were then mixed with poly(e-caprolactone) (PCL) at 5% and 10% w/w ratios and processed into fibers via electrospinning, yielding organic–inorganic nanohybrids. PCL/drug fibers were additionally prepared as controls. The average diameter of the fibers ranged from 400 to 1000 nm. The fibers are found to be smooth and cylindrical, with the LDH-containing systems having more homogenous fibers than those without the inorganic filler. From in vitro drug release tests, it was determined that more than 90% of the intercalated ibu and ket were released from the drug–LDH nanohybrids within the first 4 hours. Similarly, more than 60% of the incorporated drug was freed from the PCL/drug fibers in this time period. However, the release rates of both ibu and ket from the drug–LDH loaded PCL fibers were significantly slower. Only 44–48% of ibu was released from the PCL/ibu–LDH system after 5 days, while the amount released in the case of ket was 20–25%. In addition, drug release was still ongoing after 5 days for all the PCL/drug–LDH samples. These systems are thus proposed to have potential as implantable drug delivery systems.

Novel and highly tuneable pulsatile drug delivery systems have been prepared through the electrospinning of a blend of poly(ethylene oxide) (PEO), sodium alginate (SA), and sodium ibuprofen (SI). The resultant fibres contain crystallites of SI embedded in a PEO–SA matrix, and rather than being obtained as flat mats on the collector plate form novel three dimensional structures extending upwards the needle. Fibres were prepared with a range of loadings of SI and SA. It was found that at pH 6.8 (reminiscent of the intestinal tract) the fibres dissolve very rapidly, freeing all the embedded drug within ca. 20 minutes. However, at pH 3 (representative of the stomach pH in the fed state or in older patients) an unusual two stage release mechanism is seen. This comprises a rapid burst release, followed by a period where no further drug is released for ca. 120–150 minutes, and then a final stage of release freeing the remainder of the drug into solution. The amount of release in the initial stage, and the length of time between the first and final drug release stages, can be controlled by adjusting the SI and SA contents of the fibres respectively. This results in highly tunable pulsatile release materials.

A human panel study was performed to investigate the acceptability of orodispersible electrospun and solvent cast films. 50 healthy volunteers took two drug-free samples of polyvinyl alcohol films prepared by the two methods. On a 5-point hedonic scale, the volunteers assessed the films’ perceived size, stickiness, thickness, disintegration time, thickening effect on saliva, and handling. The films manufactured by both methods were similar in their end-user acceptability. The modal values of perceived size, thickness, disintegration time, saliva thickening effect, and handling were high (4 or 5). However, for both, the stickiness mode was 2 (strongly sticky) and the only negative attribute. Both films were reported to take approximately 30 s to disintegrate completely in the mouth. Electrospun films scored similarly high to solvent cast orodispersible films in most attributes of end-user acceptability. Electrospun films were marginally preferred, with 27 out of 50 participants picking electrospinning when presented with a forced choice test of both fabrication methods. This is the first study to show that electrospinning enables the fabrication of orodispersible films that are acceptable to adult human participants in terms of handling and mouthfeel and suggests that the potential for clinical translation of such formulations is high.

Electrospinning has emerged as a powerful strategy to develop controlled release drug delivery systems but the effects of post-fabrication solvent vapor annealing on drug-loaded electrospun fibers have not been explored to date. In this work, electrospun poly(ε-caprolactone) (PCL) fibers loaded with the hydrophobic small-molecule spironolactone (SPL) were explored. Immediately after fabrication, the fibers are smooth and cylindrical. However, during storage the PCL crystallinity in the fibers is observed to increase, demonstrating a lack of stability. When freshly-prepared fibers are annealed with acetone vapor, the amorphous PCL chains recrystallize, resulting in the fiber surfaces becoming wrinkled and yielding shish-kebab like structures. This effect does not arise after the fibers have been aged. SPL is found to be amorphously dispersed in the PCL matrix both immediately after electrospinning and after annealing. In vitro dissolution studies revealed that while the fresh fibers show a rapid burst of SPL release, after annealing more extended release profiles are observed. Both the rate and extent of release can be varied through changing the annealing time. Further, the annealed formulations are shown to be stable upon storage.

To prepare temperature and pH dual-responsive drug delivery systems, the thermosensitive polymer poly(N-isopropylacrylamide) (PNIPAAm) was first synthesized by free-radical polymerization. It was then co-dissolved with the pH-sensitive polymer Eudragit® L100-55 (EL100-55) and processed into fibers using electrospinning. Ketoprofen (KET), a model drug, was also incorporated into the composite fibers, and fibers based on a single polymer additionally prepared. The fibers had smooth cylindrical morphologies, and no obvious phase separation could be seen. Using X-ray diffraction, KET was determined to be present in the amorphous state in the fiber matrix. FTIR spectroscopy also indicated the successful incorporation of amorphous KET in the fibers. In vitro drug release studies in media at different pH (4.5 or 7.4) or temperature (25 and 37 °C) showed that the release of KET from the blend PNIPAAm/EL100-55 fibers was dependent both on environmental temperature and pH, reflecting the dual-responsive properties of the fibers. The MTT assay was used to explore the biocompatibility of the PNIPAAm/EL100-55 composite fibers towards L929 fibroblasts. Viability was always found to be >80%, even at polymer concentrations of 100 mg/L. Therefore, the fibers prepared here could lead to the development of multi-responsive materials for drug delivery and tissue engineering.

A reverse microemulsion approach has been explored for the synthesis of layered gadolinium hydroxide (LGdH) nanoparticles in this work. This method uses oleylamine as a multifunctional agent, acting as surfactant, oil phase and base. 1-butanol is additionally used as a co-surfactant. A systematic study of the key reaction parameters was undertaken, including the volume ratio of surfactant (oleylamine) to water, the reaction time, synthesis temperature, and the amount of co-surfactant (1-butanol) added. It proved possible to obtain pristine LGdH materials at temperatures of 120 °C or below with an oleylamine: water ratio of 1:4. Using larger amounts of surfactant or higher temperatures caused the formation of Gd(OH)3, either as the sole product or as a major impurity phase. The LGdH particles produced have sizes of ca. 200 nm, with this size being largely independent of temperature or reaction time. Adjusting the amount of 1-butanol co-surfactant added permits the size to be varied between 200 and 300 nm.

The objective of this work was to prepare a novel filament with good biocompatibility and mechanical performance which can meet the demands of surgical sutures. Bacterial cellulose nanocrystals (BCNCs) were used to reinforce regenerated chitin (RC) fibers to form BCNC/RC filaments. Mechanical performance measurements demonstrated that the strength of the BCNC/RC filament was increased dramatically over the RC analogue. A yarn made of 30 BCNC-loaded fibers also achieved satisfactory mechanical performance, with a knot-pull tensile strength of 9.8±0.6N. Enzymatic degradation studies showed the BCNC/RC materials to have good biodegradability, the rate of which can be tuned by varying the concentration of BCNCs in the yarn. The RC and the BCNC/RC materials had no cytotoxicity and can promote cell proliferation. In vivo experiments on mice demonstrated that suturing with the BCNC/RC yarn can promote wound healing without obvious adverse effects.

Medicines based on vascular endothelial growth factor (VEGF) neutralising antibodies such as bevacizumab have revolutionized the treatment of age related macular degeneration (AMD), a common blinding disease, and have great potential in preventing scarring after surgery or accelerating the healing of corneal injuries. However, at present frequent invasive injections are required to deliver these antibodies. Such administration is uncomfortable for patients and expensive for health service providers. Much effort is thus focused on developing dosage forms that can be administered less frequently. Here we use electrospinning to prepare a solid form of bevacizumab designed for prolonged release while maintaining antibody stability. Electrospun fibers were prepared with bevacizumab encapsulated in the core, surrounded by a poly-e-caprolactone sheath. The fibers were generated using aqueous bevacizumab solutions buffered at two different pH values: 6.2 (the pH of the commercial product; F beva ) and 8.3 (the isoelectric point of bevacizumab; F bevaP ). The fibers had smooth and cylindrical morphologies, with diameters of ca. 500 nm. Both sets of bevacizumab loaded fibers gave sustained release profiles in an in vitro model of the subconjunctival space of the eye. F beva displayed first order kinetics with t 1/2 of 11.4 ± 4.4 days, while F bevaP comprises a zero-order reservoir type release system with t 1/2 of 52.9 ± 14.8 days. Both SDS-PAGE and surface plasmon resonance demonstrate that the bevacizumab in F bevaP did not undergo degradation during fiber fabrication or release. In contrast, the antibody released from F beva had degraded, and failed to bind to VEGF. Our results demonstrate that pH control is crucial to maintain antibody stability during the fabrication of core/shell fibers and ensure release of functional protein. Statement of Significance Bevacizumab is a potent protein drug which is highly effective in the treatment of degenerative conditions in the eye. To be effective, frequent injections into the eye are required, which is deeply unpleasant for patients and expensive for healthcare providers. Alternative methods of administration are thus highly sought after. In our work, we use the electrospinning technique to prepare fiber-based formulations loaded with bevacizumab. By careful control of the experimental parameters we are able to stabilize the protein during processing and ensure a constant rate of release over more than two months in vitro . These fibers could thus be used to reduce the frequency of dosing required, reducing cost and improving patient outcomes.

In this work, we report electrospun nanofibers made of model hydrophobic (poly(lactide-co-ε-caprolactone); PLCL) and hydrophilic (gelatin) polymers. We explored the effect on drug release of the incorporation of sodium bicarbonate (SB) into these fibers, using the potent antibacterial agent ciprofloxacin as a model drug. The fibers prepared are smooth and have relatively uniform diameters lying between ca. 600 and 850nm. The presence of ciprofloxacin in the fibers was confirmed using IR spectroscopy. X-ray diffraction showed the drug to be incorporated into the fibers in the amorphous form. In vitro drug release studies revealed that, as expected, more rapid drug release was seen with gelatin fibers than those made of PLCL, and a greater final release percentage was obtained. The inclusion of SB in the gelatin fibers imparts them with pH sensitivity: gelatin/SB fibers showed faster release at pH5 than pH7.4, while fibers without SB gave the same release profiles at both pHs. The PLCL fibers have no pH sensitivity, even when SB was included, as a result of their hydrophobic structure precluding the ingress of solvent. In vitro cell culture studies showed that all the fibers are able to promote cell proliferation. The ciprofloxacin loaded fibers are effective in inhibiting Escherichia coli and Staphylococcus aureus growth in antibacterial tests. Thus, the gelatin-based fibers can be used as pH-responsive drug delivery systems, with potential applications for instance in the treatment of tumor resection sites. Should these become infected, the pH would drop, resulting in ciprofloxacin being released and the infection halted.

Most conventional chemotherapeutics have narrow therapeutic windows, and thus their delivery remains challenging and often raises safety and efficacy concerns. Theranostic platforms, with simultaneous encapsulation of therapeutic and diagnostic agents, have been proposed as next-generation formulations which can overcome this issue. In this work, we used electrohydrodynamic approaches to fabricate core@shell formulations comprising a pH responsive Eudragit L100 shell embedded with superparamagnetic iron oxide nanoparticles (SPIONs), and a thermo-responsive poly(N-isopropylacrylamide) (PNIPAM)/ethyl cellulose core loaded with the model drug carmofur. By varying the weight ratio of core polymer to shell polymer, the morphology of PNIPAM/ethyl cellulose@Eudragit L100 microparticles could be changed from concave to spherical. Smooth cylindrical fibres could also be generated. All the formulations exist as amorphous solid dispersions of drug-in-polymer, with distinct core@shell architectures. The fibres have clear thermo-responsive drug release profiles, while no thermo-responsive properties can be seen with the particles. All the formulations can protect SPIONs from degradation in gastric fluids (pH ∼ 1.5), and around the physiological pH range the materials offer effective and pH-responsive relaxivity. The r2 values also display clear linear relationships with drug release data, suggesting the potential of using MRI signals to track drug release in vivo. Mathematical equations were established to track drug release in vitro, with very similar experimental and predicted release profiles obtained.

Objective. The use of diffusion magnetic resonance imaging (dMRI) opens the door to characterizing brain microstructure because water diffusion is anisotropic in axonal fibres in brain white matter and is sensitive to tissue microstructural changes. As dMRI becomes more sophisticated and microstructurally informative, it has become increasingly important to use a reference object (usually called an imaging phantom) for validation of dMRI. This study aims to develop axon-mimicking physical phantoms from biocopolymers and assess their feasibility for validating dMRI measurements. Approach. We employed a simple and one-step method—coaxial electrospinning—to prepare axon-mimicking hollow microfibres from polycaprolactone-b-polyethylene glycol (PCL-b-PEG) and poly(D, L-lactide-co-glycolic) acid (PLGA), and used them as building elements to create axon-mimicking phantoms. Electrospinning was firstly conducted using two types of PCL-b-PEG and two types of PLGA with different molecular weights in various solvents, with different polymer concentrations, for determining their spinnability. Polymer/solvent concentration combinations with good fibre spinnability were used as the shell material in the following co-electrospinning process in which the polyethylene oxide polymer was used as the core material. Following the microstructural characterization of both electrospun and co-electrospun fibres using optical and electron microscopy, two prototype phantoms were constructed from co-electrospun anisotropic hollow microfibres after inserting them into water-filled test tubes. Main results. Hollow microfibres that mimic the axon microstructure were successfully prepared from the appropriate core and shell material combinations. dMRI measurements of two phantoms on a 7 tesla (T) pre-clinical scanner revealed that diffusivity and anisotropy measurements are in the range of brain white matter. Significance. This feasibility study showed that co-electrospun PCL-b-PEG and PLGA microfibre-based axon-mimicking phantoms could be used in the validation of dMRI methods which seek to characterize white matter microstructure.

Previous preclinical and clinical studies have shown that using only a single therapy makes it difficult to completely eradicate tumors and restrain cancer metastasis. To overcome this challenge, multi-modal synergistic treatments have attracted considerable attention. Herein, an ultrathin Cu-loaded CoCuFe-selenide (CCFS) was prepared by a facile topotactic transformation from CoCuFe layered double hydroxide (LDH) nanosheets (NSs), followed by surface modification with polyvinyl pyrrolidone (PVP) and l-arginine (L-Arg). The resultant CCFS-PVP-L-Arg (CPA) system shows excellent synergetic photothermal and gas therapy (PTT/GT). The CCFS NSs have strong LSPR absorbance characteristic, with enhanced light absorption in the near-infrared (NIR) region. This endows the CPA nanocomposite with an outstanding photothermal conversion efficiency of 72.0% (pH 7.4) and 81.0% (pH 5.4), among the highest reported for 2D chalcogenide nanomaterials. In addition, NO release from CPA is triggered by decomposition of L-Arg in the H2O2-rich and acidic tumor microenvironment, permitting localized NO gas therapy in the tumor site. In vitro experiments revealed 91.8% apoptosis of HepG2 cells, and in vivo studies showed complete tumor elimination upon treatment with the CPA nanocomposite under NIR irradiation. To the best of our knowledge, this is the first report of combined defect-induced high-efficiency PTT with H2O2 and pH targeted GT.

In this study, the thermosensitive polymer poly(di(ethylene glycol) methyl ether methacrylate) (PDEGMA) was synthesized and electrospun into fibers by blending with ethyl cellulose (EC). Fibers were additionally prepared loaded with ketoprofen (KET) as a model drug. Smooth cylindrical fibers could generally be observed by electron microscopy, although there were some beads and fused fibers visible in the KET-loaded materials. KET was found to be amorphously distributed in the fibers on the basis of X-ray diffraction data. From water contact angle measurements, it was clear that the wettability of the EC/PDEGMA systems changed as the temperature increased, with the fibers becoming markedly more hydrophobic. In vitro drug release studies showed that KET was released over a prolonged period of time with the fibers having different profiles at 25 and 37°C, reflecting their thermosensitive properties. Furthermore, the materials were found to have good biocompatibility towards L929 fibroblasts. Thus, the fibers prepared in this work have potential as smart stimuli-responsive drug delivery systems.

Nanoscale drug depots, comprising a drug reservoir surrounded by a carrier membrane, are much sought after in contemporary pharmaceutical research. Using cellulose acetate (CA) as a filament-forming polymeric matrix and ferulic acid (FA) as a model drug, nanoscale drug depots in the form of core-shell fibers were designed and fabricated using a modified tri-axial electrospinning process. This employed a solvent mixture as the outer working fluid, as a result of which a robust and continuous preparation process could be achieved. The fiber-based depots had a linear morphology, smooth surfaces, and an average diameter of 0.62 ± 0.07 μm. Electron microscopy data showed them to have clear core-shell structures, with the FA encapsulated inside a CA shell. X-ray diffraction and IR spectroscopy results verified that FA was present in the crystalline physical form. In vitro dissolution tests revealed that the fibers were able to provide close to zero-order release over 36 h, with no initial burst release and minimal tailing-off. The release properties of the depot systems were much improved over monolithic CA/FA fibers, which exhibited a significant burst release and also considerable tailing-off at the end of the release experiment. Here we thus demonstrate the concept of using modified tri-axial electrospinning to design and develop new types of heterogeneous nanoscale biomaterials. Statement of Significance Nanoscale drug depots with a drug reservoir surrounded by a carrier are highly attractive in biomedicine. A cellulose acetate based drug depot was investigated in detail, starting with the design of the nanostructure, and moving through its fabrication using a modified tri-axial electrospinning process and a series of characterizations. The core-shell fiber-based drug depots can provide a more sustained release profile with no initial burst effect and less tailing-off than equivalent monolithic drug-loaded fibers. The drug release mechanisms are also distinct in the two systems. This proof-of-concept work can be further expanded to conceive a series of new structural biomaterials with improved or new functional performance.

The most important property of a wound dressing is its anti-bacteria performance. Although electrospun nanofibers are frequently demonstrated to be potent candidates as wound dressings, no Janus fibers have been explored for this popular application. In this study, a Janus wound dressing composed of polyvinylpyrrolidone (PVP) and ethyl cellulose (EC) polymer matrices was prepared via a side-by-side electrospinning process, in which ciprofloxacin (CIP) and silver nanoparticles (AgNPs) were loaded in the two sides. A homemade acentric spinneret was exploited to maintain a continuous preparation process. Scanning and transmission electron microscope results demonstrated that the Janus fibers had a uniform and cylindrical morphology with a clear Janus structure, and AgNPs distributed in one side. X-ray diffraction patterns suggested that drug was present in the fibers in an amorphous state owing to rapid drying and its good compatibility with PVP, which was verified by infrared spectroscopy. In vitro tests showed that over 90% of CIP was released within the first 30 min, ensuring a strong antibacterial effect at the initial stages of wound healing. The Janus fibers were demonstrated to have good bactericidal activity against the growth of both Gram-positive S. aureus and Gram-negative E. coli. The PVP-CIP/EC-AgNPs Janus fibers could thus be a promising candidate for effective wound dressings. This work paves a new way for creating Janus structure-based advanced functional nanomaterials.

There is great market demand for fabrics equipped with multiple functionalities. However, most methods to impart these properties to a pristine fabric are complicated, time-consuming, and expensive. In this work, Janus particles with one side comprising TiO2 nanoparticles (NPs)-PVDF (poly (vinylidene fluoride)) and the other an epoxy resin (TPE) were deposited on a fabric surface. The aim was to endow the fabric with the superhydrophobic, UV resistance, and antimicrobial properties. The Janus particles were firmly attached to the fabrics through the adhesion effects of the epoxy resin. Characterization by XRD, SEM, EDX, and FTIR verified the successful finishing of the fabric with TPE particles. The ultraviolet protection factor increased from 7.86 for the pristine fabric to 733 after finishing. The finished fabric also exhibited superhydrophobic properties, with a water contact angle of 152°. Further, the coating of the fabric did not hamper its gas permeability. Potent antibacterial properties against E. coli were observed owing to the antibacterial properties of TiO2 under pre-irradiation by UV light. The protocols reported here provide a new platform for the nano-finishing of fabrics, allowing new functions to be imparted without compromising.

Fluoride pollution of water is a matter of concern in many countries due to its association with chronic kidney failure. Therefore, it is important to develop fast and efficient methods for fluoride removal from drinking water using environmentally friendly materials. In this article, the synthesis, characterization and microwave assisted accelerated fluoride removal by porous nanohydroxyapatite (PHAP) are reported. The PHAP samples were synthesized using polyvinyl pyrrolidone and sodium dodecyl sulphate micellar system as the template. The prepared nanohydroxyapatite was characterized using TEM, SEM, FT-IR, TGA, XRD and BET. Investigation of the morphology of microcrystals using TEM showed the presence of spherical particles of 20–35 nm size and highly porous rod-shaped crystals with the aspect ratio of 2:13. The adsorption of F− ions using PHAP was carried out under the influence of microwave radiations using concentrations comparable to existing F− levels in natural water. The equilibrium is reached within 80 s and this is the fastest saturation time recorded for any existing material. The kinetic experiments showed that the fluoride adsorption is an activated second order process. The equilibrium fluoride adsorption capacity of PHAP was found to be 9.19 mg g−1 at pH 6.5 for 80 s and this was proven to be a potential material to remove F− ions rapidly from drinking water.

Extracellular vesicles (EVs) are cell-derived bodies proven to have a wide range of therapeutic applications. To date, EVs have almost always been administered by direct injection, which is very likely to hinder their efficacy because of rapid clearance from the injection site. Here we show that EVs can be successfully processed into polymer-based fibres by electrospinning, with no loss of structure or function.

The tissue integration of synthetic polymers can be promoted by displaying RGD peptides at the biointerface with the objective of enhancing colonization of the material by endogenous cells. A firm but flexible attachment of the peptide to the polymer matrix, still allowing interaction with receptors, is therefore of interest. Here, the covalent coupling of flexible physical anchor groups, allowing for temporary immobilization on polymeric surfaces via hydrophobic or dipole–dipole interactions, to a RGD peptide was investigated. For this purpose, a stearate or an oligo(ethylene glycol) (OEG) was attached to GRGDS in 51–69% yield. The obtained RGD linker constructs were characterized by NMR, IR and MALDI-ToF mass spectrometry, revealing that the commercially available OEG and stearate linkers are in fact mixtures of similar compounds. The RGD linker constructs were co-electrospun with poly(p-dioxanone) (PPDO). After electrospinning, nitrogen could be detected on the surface of the PPDO fibers by X-ray photoelectron spectroscopy. The nitrogen content exceeded the calculated value for the homogeneous material mixture suggesting a pronounced presentation of the peptide on the fiber surface. Increasing amounts of RGD linker constructs in the electrospinning solution did not lead to a detection of an increased amount of peptide on the scaffold surface, suggesting inhomogeneous distribution of the peptide on the PPDO fiber surface. Human adipose-derived stem cells cultured on the patches showed similar viability as when cultured on PPDO containing pristine RGD. The fully characterized RGD linker constructs could serve as valuable tools for the further development of tissue-integrating polymeric scaffolds. Copyright © 2016 John Wiley & Sons, Ltd.

A modified tri-axial electrospinning process was developed for the generation of a new type of pH-sensitive polymer/lipid nanocomposite. The systems produced are able to promote both dissolution and permeation of a model poorly water-soluble drug. First, we show that it is possible to run a tri-axial process with only one of the three fluids being electrospinnable. Using an electrospinnable middle fluid of Eudragit S100 (ES100) with pure ethanol as the outer solvent and an unspinnable lecithin-diclofenac sodium (PL-DS) core solution, nanofibers with linear morphology and clear core/shell structures can be fabricated continuously and smoothly. X-ray diffraction proved that these nanofibers are structural nanocomposites with the drug present in an amorphous state. In vitro dissolution tests demonstrated that the formulations could preclude release in acidic conditions, and that the drug was released from the fibers in two successive steps at neutral pH. The first step is the dissolution of the shell ES100 and the conversion of the core PL-DS into sub-micron sized particles. This frees some DS into solution, and later the remaining DS is gradually released from the PL-DS particles through diffusion. Ex vivo permeation results showed that the composite nanofibers give a more than twofold uplift in the amount of DS passing through the colonic membrane as compared to pure DS; 74% of the transmitted drug was in the form of PL-DS particles. The new tri-axial electrospinning process developed in this work provides a platform to fabricate structural nanomaterials, and the core-shell polymer-PL nanocomposites we have produced have significant potential applications for oral colon-targeted drug delivery.A modified tri-axial electrospinning is demonstrated to create a new type of core-shell pH-sensitive polymer/lipid nanocomposites, in which an electrospinnable middle fluid is exploited to support the un-spinnable outer and inner fluids. The structural nanocomposites are able to provide a colon-targeted sustained release and an enhanced permeation performance of diclofenac sodium. The developed tri-axial process can provide a platform for fabricating new structural nanomaterials with high quality. The strategy of a combined usage of polymeric excipients and phospholipid in a core-shell format should provide new possibilities of developing novel drug delivery systems for efficacious oral administration of poorly-water soluble drugs.

A family of medicated Janus fibers that provides highly tunable biphasic drug release was fabricated using a side-by-side electrospinning process employing a Teflon-coated parallel spinneret. The coated spinneret facilitated the formation of a Janus Taylor cone and in turn high quality integrated Janus structures, which could not be reliably obtained without the Teflon coating. The fibers prepared had one side consisting of polyvinylpyrrolidone (PVP) K60 and ketoprofen, and the other of ethyl cellulose (EC) and ketoprofen. To modulate and tune drug release, PVP K10 was doped into the EC side in some cases. The fibers were linear and had flat morphologies with an indent in the center. They provide biphasic drug release, with the PVP K60 side dissolving very rapidly to deliver a loading dose of the active ingredient, and the EC side resulting in sustained release of the remaining ketoprofen. The addition of PVP K10 to the EC side was able to accelerate the second stage of release; variation in the dopant amount permitted the release rate and extent this phase to be precisely tuned. These results offer the potential to rationally design systems with highly controllable drug release profiles, which can complement natural biological rhythms and deliver maximum therapeutic effects.

Two biocompatible hydroxy double salts (HDSs) were synthesised for the first time and loaded with active pharmaceutical ingredients. Drug release was studied from these intercalates, and sustained release observed. The HDS-drug composites were further formulated into tablets which were found to comply with pharmacopeia requirements for delayed and extended release dosage forms.

Transition metal dichalcogenides (TMDs) have received considerable attention due to their strong absorption in the near‐infrared (NIR) region, strong spin‐orbit coupling, and excellent photothermal conversion efficiency (PCE). Herein, CoFeMn dichalcogenide nanosheets (CFMS NSs) are prepared via facile vulcanization of a lamellar CoFeMn‐layered double hydroxide (LDH) precursor followed by polyvinyl pyrrolidone modification (to give CFMS‐PVP NSs), and found to show excellent photoacoustic (PA) imaging and synergistic photothermal/chemodynamic therapy (PTT/CDT) performance. The as‐prepared CFMS‐PVP NSs inherit the ultrathin morphology of the CoFeMn‐LDH precursor and exhibit an outstanding photothermal performance with a η of 89.0%, the highest PCE reported to date for 2D TMD materials. Moreover, 50% of maximum catalytic activity (Michaelis–Menten constant, K m) is attained by CFMS‐PVP NSs with 0.26 × 10−3 m H2O2 at 318 K, markedly lower than the endogenous concentration of H2O2 inside tumor cells. In addition, complete apoptosis of HepG2 cancer cells and complete tumor elimination in vivo are observed after treatment with CFMS‐PVP NSs at a low dose, substantiating the NSs’ remarkable PTT/CDT efficacy. This work provides a new and facile approach for the synthesis of high‐quality multicomponent TMD nanosheets with precise process control, the potential for mass production, and outstanding performance, providing great promise in cancer theranostics., A highly tunable polyvinyl pyrrolidone modified CoFeMn dichalcogenide nanosheets (CFMS‐PVP NSs) platform is fabricated via facile vulcanization of lamellar CoFeMn‐layered double hydroxide precursor, which shows outstanding photothermal conversion efficiency (η = 89.0%), effective photoacoustic imaging and synergistic photothermal/chemodynamic therapy.

Layered gadolinium hydroxides (LGdH) have significant potential in simultaneous drug delivery and magnetic resonance imaging (MRI). In this work, we synthesized LGdH nanocomposites surface functionalised with SiO2 nanodots (LGdH@SiO2). We find these to have good dispersibility in cell culture medium, and a reduced tendency to aggregate compared to their uncoated analogue. Under the optimal reaction conditions, SiO2 nanodots were evenly spread across the surface of the LGdH particles. We further intercalated ibuprofen (Ibu) and 5-fluorouracil (5FU) into LGdH@SiO2, and explored the use of the resultant composites for drug delivery in vitro. While the SiO2 coating could effectively reduce aggregation of the Ibu intercalate prepared by ion exchange from the parent LGdH, it was noted to increase aggregation in the case of the 5FU-loaded systems produced by coprecipitation. With a SiO2 coating, 5FU release from the composite was almost zero-order at pH 7.4. The LGdH-5FU@SiO2 composites can effectively inhibit the growth of A549 ​cells (a human adenocarcinoma cell line). In contrast, the Ibu-loaded materials are highly biocompatible. After SiO2 modification, LGdH-5FU@SiO2 retains the same proton relaxivity properties as LGdH-5FU, while LGdH-Ibu@SiO2 becomes suitable for use as a negative contrast agent in MRI.

Electrospinning is a potent “top-down” nanofabrication method and has been explored by many researchers in recent decades because it is an efficient, versatile, simple, and low-cost route to prepare nanofibers. Nanofiber membranes generated by electrospinning have been used in various fields including tissue engineering, wound dressing, biosensing, theranostics, and functional textiles. Here we summarize the development of multifluid electrospinning processes, including coaxial, Janus and triaxial electrospinning, and the applications of these techniques. Complex nanostructures prepared by multifluid electrospinning are considered. The key parameters that affect the electrospinning process are introduced, and a discussion of both equipment and solution parameters is presented.

In this study, novel core-shell nanostructures were fabricated through a modified triaxial electrospinning process. These comprised a drug-protein nanocomposite coated with a thin cellulose acetate (CA) shell. They were generated through the simultaneous treatment of an outer solvent, an unelectrospinnable middle fluid, and an electrospinnable core solution in triaxial electrospinning. SEM and TEM results revealed that the core-shell nanofibers had linear and cylindrical morphologies with a diameter from 0.66 to 0.87 μm, and distinct core-shell structures with a shell thickness from 1.8 to 11.6 nm. The presence of a CA coating eliminated the initial burst release of ibuprofen seen from a monolithic drug-protein composite, and allowed us to precisely manipulate the drug release (for a 90% percentage) over a time period from 23.5 to 43.9 h in a tunable manner. Mathematical relationships between the processing conditions, the nanostructures produced, and their functional performance were elucidated.

Strategies to surface‐functionalize scaffolds by covalent binding of biologically active compounds are of fundamental interest to control the interactions between scaffolds and biomolecules or cells. Poly(para‐dioxanone) (PPDO) is a clinically established polymer that has shown potential as temporary implant, eg, for the reconstruction of the inferior vena cava, as a nonwoven fiber mesh. However, PPDO lacks suitable chemical groups for covalent functionalization. Furthermore, PPDO is highly sensitive to hydrolysis, reflected by short in vivo half‐life times and degradation during storage. Establishing a method for covalent functionalization without degradation of this hydrolyzable polymer is therefore important to enable the surface tailoring for tissue engineering applications. It was hypothesized that treatment of PPDO with an N‐hydroxysuccinimide ester group bearing perfluorophenyl azide (PFPA) under UV irradiation would allow efficient surface functionalization of the scaffold. X‐ray photoelectron spectroscopy and attenuated total reflectance Fourier‐transformed infrared spectroscopy investigation revealed the successful binding, while a gel permeation chromatography study showed that degradation did not occur under these conditions. Coupling of a rhodamine dye to the N‐hydroxysuccinimide esters on the surface of a PFPA‐functionalized scaffold via its amine linker showed a homogenous staining of the PPDO in laser confocal microscopy. The PFPA method is therefore applicable even to the surface functionalization of hydrolytically labile polymers, and it was demonstrated that PFPA chemistry may serve as a versatile tool for the (bio‐)functionalization of PPDO scaffolds.

A series of 5-fluorouracil (5-FU) loaded core/shell electrospun fibers is reported. The fibers have shells made of Eudragit S100 (ES-100), and drug-loaded cores comprising poly(vinylpyrrolidone), ethyl cellulose, ES-100, or drug alone. Monolithic 5-FU loaded ES-100 fibers were also prepared for comparison. Electron microscopy showed all the fibers to have smooth cylindrical shapes, and clear core-shell structures were visible for all samples except the monolithic fibers. 5-FU was present in the amorphous physical form in all the materials prepared. Dissolution studies showed that the ES-100 shell was not able to prevent drug release at pH 1.0, even though the polymer is completely insoluble at this pH: around 30-80% of the maximum drug release was reached after 2h immersion at pH 1.0. These observations are ascribed to the low molecular weight of 5-FU permitting it to diffuse through pores in the ES-100 coating, and the relatively high acid solubility of the drug providing a thermodynamic impetus for this to happen. In addition, the fibers were observed to be broken or merged following 2h at pH 1.0, giving additional escape routes for the 5-FU.

The present study reports a new type of sedative nanofiber membranes that were developed to permit very rapid oral delivery of helicid with concomitant taste masking. A coaxial electrospinning process was exploited to prepare core–shell nanofibers and to control the spatial depositions of different functional components. A series of tests was undertaken to characterize the resultant nanofibers. Following optimization of the electrospinning parameters, two types of core–shell nanofibers with average diameters of 730 ± 140 and 770 ± 160 nm were successfully prepared. These had uniform linear morphologies and clear core–shell structures, as verified by scanning and transmission electron microscopy images. The fibers contained sucralose in the shell and helicid in the core; X-ray diffraction demonstrated that both functional components were present in the amorphous physical form. There is significant hydrogen bonding between the functional components and the poly(vinylpyrrolidone) used as the carrier matrix, as shown from Fourier transform infrared spectroscopy and molecular mechanics simulations. In vitro dissolution tests showed that the formulations were able to release the entire incorporated drug extremely rapidly (within 1 min) when they encountered a dissolution medium, whereas the commercially available product released only 13.4 % of its drug loading in the same time. By tailoring the distribution of functional ingredients in electrospun core–shell structures, new drug delivery systems which can both accelerate dissolution and also mask unpleasant tastes were produced.

When formulated as liquid dosage forms, therapeutic proteins and peptides often show instability during handling as a result of chemical degradation. Solid formulations are frequently required to maintain protein stability during storage, transport and upon administration. Herein we highlight current strategies used to formulate pharmaceutical proteins in the solid form. An overview of the physical instabilities which can arise with proteins is first described. The key solidification techniques of crystallization, freeze-drying and particle forming technologies are then discussed. Examples of current commercial products that are formulated in the solid state are provided and include neutral protamine Hagedorn – insulin crystal suspensions, freeze-dried monoclonal antibodies and leuproride polylactide-co-glycolide microparticles. Finally, future perspectives in solid-state protein formulation are described.

A series of polyvinylpyrrolidone fibers loaded with paracetamol (PCM) and caffeine (CAF) was fabricated by electrospinning and explored as potential oral fast-dissolving films. The fibers take the form of uniform cylinders with smooth surfaces, and contain the drugs in the amorphous form. Drug-polymer intermolecular interactions were evidenced by infrared spectroscopy and molecular modeling. The properties of the fiber mats were found to be highly appropriate for the preparation of oral fast dissolving films: their thickness is around 120-130 μm, and the pH after dissolution in deionized water lies in the range of 6.7-7.2. Except at the highest drug loading, the folding endurance of the fibers was found to be >20 times. A flavoring agent can easily be incorporated into the formulation. The fiber mats are all seen to disintegrate completely within 0.5s when added to simulated saliva solution. They release their drug cargo within around 150s in a dissolution test, and to undergo much more rapid dissolution than is seen for the pure drugs. The data reported herein clearly demonstrate that electrospun PCM/CAF fibers comprise excellent candidates for oral fast-dissolving films, which could be particularly useful for children and patients with swallowing difficulties.

A structured spinneret comprising two acentric needles nested into a third metal capillary was developed to conduct three-fluid electrospinning processes. With an exterior solvent surrounding two core fluids arranged side-by-side, high quality polyvinylpyrrolidone/shellac Janus nanofibers could be prepared, which was not possible using a standard side-by-side spinneret without this innovation.

Electrospinning was used to prepare core/shell fibers containing the active pharmaceutical ingredients indomethacin (IMC) or mebeverine hydrochloride (MB-HCl). The shell of the fibers was fabricated from the pH sensitive Eudragit S100 polymer, while the drug-loaded core was based on the mucoadhesive poly(ethylene oxide) (PEO). Three different drug loadings (from 9 to 23% (w/w) of the core mass) were prepared, and for MB-HCl two different molecular weights of PEO were explored. The resultant fibers generally comprise smooth cylinders, although in some cases defects such as surface particles or flattened or merged fibers were visible. Transmission electron microscopy showed all the systems to have clear core and shell compartments. The drugs are present in the amorphous physical form in the fibers. Dissolution tests found that the fibers can effectively prevent release in acidic conditions representative of the stomach, particularly for the acidic indomethacin. After transfer to a pH 7.4 medium, sustained release over between 6 and 22h is observed. Given the mucoadhesive nature of the PEO core, after dissolution of the shell the fibers will be able to adhere to the walls of the intestinal tract and give sustained local drug release. This renders them promising for the treatment of conditions such as irritable bowel disease and colon cancer.

The performances of pseudocapacitors usually depend heavily on their hierarchical architectures and composition. Herein, we report a three-dimensional hierarchical NiAl layered double hydroxide/multiwalled carbon nanotube/nickel foam (NiAl-LDH/MWCNT/NF) electrode prepared by a facile three-step fabrication method: in situ hydrothermal growth of NiAl-LDH film on a Ni foam, followed by direct chemical vapor deposition growth of dense MWCNTs onto the NiAl-LDH film, and finally the growth of NiAl-LDH onto the surface of the MWCNTs via an in situ hydrothermal process in the presence of surfactant sodium dodecyl sulfate. The MWCNT surface was fully covered by NiAl-LDH hexagonal platelets, and this hierarchical architecture led to a much enhanced capacitance. The NiAl-LDH/MWCNT/NF electrode has an areal loading mass of 5.8 mg of LDH per cm(2) of MWCNT/NF surface. It also possesses exceptional areal capacitance (7.5 F cm(-2)), specific capacitance (1293 F g(-1)), and cycling stability (83% of its initial value was preserved after 1000 charge-discharge cycles). The NiAl-LDH/MWCNT/NF material is thus a highly promising electrode with potential applications in electrochemical energy storage.

A new and facile route for preparing magnetic liposomes from electrospun fibers comprising the hydrophilic polymer polyvinylpyrrolidone K90, phosphatidyl choline and Fe 3 O 4 nanoparticles is reported. The composite fibers were found to contain Fe 3 O 4 particles dispersed relatively uniformly. Magnetic liposomes formed spontaneously via molecular self-assembly when the composite fibers were added to water. The liposomes were found to be generally well dispersed, and stable to degradation. Their size can be controlled by varying the Fe 3 O 4 content of the fibers. The magnetic properties of the nanoparticles are maintained through the electrospinning and self-assembly processes, indicating that these materials maybe have very considerable potential in the development of magnetic drug delivery systems and other therapeutic or theranostic applications.