Nicholas P. Chatterton

Electrospun diclofenac sodium loaded Eudragit® L 100-55 nanofibers for colon-targeted drug delivery

Eudragit® L 100-55 nanofibers loaded with diclofenac sodium (DS) were successfully prepared using an electrospinning process, and characterized for structural and pharmacodynamic properties. The influence of solvent and drug content on fiber formation and quality was also investigated. Fiber formation was successful using a solvent mixture 5:1 (v/v) ethanol:DMAc. XRD and DSC analysis of fibers confirm electron microscopic evidence that DS is evenly distributed in the nanofibers in an amorphous state. FTIR analysis indicates hydrogen bonding occurs between the drug and the polymer, which accounts for the molecular integration of the two components. In vitro dissolution tests verified that all the drug-loaded Eudragit® L 100-55 nanofibers had pH-dependent drug release profiles, with limited, less than 3%, release at pH 1.0, but a sustained and complete release at pH 6.8. This profile of properties indicates drug-loaded Eudragit® L 100-55 nanofibers have the potential to be developed as oral colon-targeted drug delivery systems.

Improving polymer nanofiber quality using a modified co-axial electrospinning process

Based on a modified coaxial electrospinning process and suitable selection of solvent mixtures as sheath fluid, a new strategy is presented for systematically improving polymer nanofiber quality. A concentric spinneret with an indented inner capillary is designed for the modified coaxial electrospinning. With a solution of 12% w/v PVP K60 in ethanol as the core electrospinning fluid, six solvents are used as sheath fluids to investigate the impact of solvent properties on the resultant PVP nanofiber quality. The PVP nanofiber quality is closely related to solvent physical-chemical properties. High quality PVP nanofibers of average diameter 130 ±10 nm with homogeneous structures and smooth surfaces are created using a solvent mixture of acetone, ethanol and DMAc in the ratio of 3:1:1(v/v/v).

Self-assembled liposomes from amphiphilic electrospun nanofibers

Amphiphilic nanofibers composed of the hydrophilic polymer polyvinylpyrrolidone K60 (PVP) and soybean lecithin were fabricated using an electrospinning process. As a result of the templating and confinement properties of the nanofibers, phosphatidyl choline (PC) liposomes were spontaneously formed through molecular self-assembly when the fibers were added to water. The sizes of the self-assembled liposomes could be manipulated by varying the content of PC in the nanofibers (over the range 9.1–33.3% (w/w) in the present study). The influence of PC on nanofiber formation, and a possible mechanism of templated liposome formation are discussed. This facile and convenient strategy for manipulating molecular self-assembly to synthesize liposomes provides a versatile new approach for the development of novel drug delivery systems and biomaterials.

Preparation of core-shell PAN nanofibers encapsulated α-tocopherol acetate and ascorbic acid 2-phosphate for photoprotection

Magnesium l-ascorbic acid 2-phosphate (MAAP) and α-tocopherol acetate (α-TAc), as the stable vitamin C and vitamin E derivative, respectively, are often applied to skin care products for reducing UV damage. The encapsulation of MAAP (0.5%, g/mL) and α-TAc (5%, g/mL) together within the polyacrylonitrile (PAN) nanofibers was demonstrated using a coaxial electrospinning technique. The structure and morphology characterizations of the core-shell fibers MAAP/α-TAc-PAN were investigated by SEM, FTIR and XRD. As a negative control, the blend nanofibers MAAP/α-TAc/PAN were prepared from a normal electrospinning method. The results from SEM indicated that the morphology and diameter of the nanofibers were influenced by concentration of spinning solution, the polymer component of the shell, the carrying agent of the core and the fabricating methods, and the core-shell nanofibers obtained at the concentration of 8% had finer and uniform structure with the average diameters of 200 ± 15nm. From in vitro release studies it could be seen that both different fiber specimens showed a gradual increase in the amount of α-TAc or MAAP released from the nanofibers. Furthermore, α-TAc and MAAP released from the blend nanofibers showed the burst release at the maximum release of ∼15% and ∼40% during the first 6h, respectively, but their release amount from the core-shell nanofibers was only 10-12% during the initial part of the process. These results showed that core-shell nanofibers alleviated the initial burst release and gave better sustainability compared to that of the blend nanofibers. The present study would provide a basis for further optimization of processing conditions to obtain desired structured core-shell nanofibers and release kinetics for practical applications in dermal tissue.

Fast dissolving paracetamol/caffeine nanofibers prepared by electrospinning

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.

Polyacrylonitrile nanofibers coated with silver nanoparticles using a modified coaxial electrospinning process

Background The objective of this investigation was to develop a new class of antibacterial material in the form of nanofibers coated with silver nanoparticles (AgNPs) using a modified coaxial electrospinning approach. Through manipulation of the distribution on the surface of nanofibers, the antibacterial effect of Ag can be improved substantially. Methods Using polyacrylonitrile (PAN) as the filament-forming polymer matrix, an electrospinnable PAN solution was prepared as the core fluid. A silver nitrate (AgNO3) solution was exploited as sheath fluid to carry out the modified coaxial electrospinning process under varied sheath-to-core flow rate ratios. Results Scanning electron microscopy and transmission electron microscopy demonstrated that the sheath AgNO3 solution can take a role in reducing the nanofibers’ diameters significantly, a sheath-to-core flow rate ratio of 0.1 and 0.2 resulting in PAN nanofibers with diameters of 380 ± 110 nm and 230 ± 70 nm respectively. AgNPs are well distributed on the surface of PAN nanofibers. The antibacterial experiments demonstrated that these nanofibers show strong antimicrobial activities against Bacillus subtilis Wb800, and Escherichia coli dh5α. Conclusion Coaxial electrospinning with AgNO3 solution as sheath fluid not only facilitates the electrospinning process, providing nanofibers with reduced diameters, but also allows functionalization of the nanofibers through coating with functional ingredients, effectively ensuring that the active antibacterial component is on the surface of the material, which leads to enhanced activity. We report an example of the systematic design, preparation, and application of a novel type of antibacterial material coated with AgNPs via a modified coaxial electrospinning methodology.

Structural lipid nanoparticles self-assembled from electrospun core-shell polymeric nanocomposites

Electrospun polymeric core–shell nanocomposites are exploited as templates to manipulate molecular self-assembly for preparing structural lipid nanoparticles, during which the confinement effect of fibers together with their core–shell structure, the aqueous environment and the secondary interactions, all contributed synergistically to facilitate molecular self-aggregation to produce lipid nanoparticles with a drug entrapment efficiency of 95.9% with a sustained drug release profile.

Mebeverine‐Loaded Electrospun Nanofibers: Physicochemical Characterization and Dissolution Studies

Both fast dissolving and sustained release drug delivery systems (DDSs) comprising mebeverine hydrochloride (MB-HCl) embedded in either povidone (PVP) K60 or Eudragit(®) L 100-55 nanofibers have been prepared by electrospinning. The fibers are found to have cylindrical morphologies with smooth surfaces, except at high drug loadings that appear to induce surface roughness (PVP) or fragmentation (Eudragit). There is a general increase in fiber diameter with drug loading. Differential scanning calorimetry and X-ray diffraction demonstrate that the drug exists in an amorphous state in the fibers. Infrared spectroscopy data indicate that the drug has good compatibility with the polymer, whereas nuclear magnetic resonance spectroscopy and high-performance liquid chromatography analyses confirmed that the MB-HCl was not degraded during the spinning process. In vitro dissolution tests of the PVP fiber mats show them to dissolve within 10 s, an improved dissolution profile over the pure drug. The Eudragit fibers show pH-dependent drug release profiles, with only very limited release at pH 2.0 but sustained release over approximately 8 h at pH 6.8. The Eudragit nanofibers have the potential to be developed as oral DDSs for localized drug release in the intestinal tract, whereas the PVP materials may find the application as buccal delivery systems or suppositories.

5-Fluorouracil loaded Eudragit fibers prepared by electrospinning

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.

Pulsatile drug release from electrospun poly(ethylene oxide)–sodium alginate blend nanofibres

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.