Gareth R. Williams

Modified coaxial electrospinning for the preparation of high-quality ketoprofen-loaded cellulose acetate nanofibers

This study investigates the use of a modified coaxial electrospinning process in the production of drug-loaded cellulose acetate (CA) nanofibers. With CA employed as a filament-forming matrix and ketoprofen (KET) as an active pharmaceutical ingredient, modified coaxial processes using sheath fluids comprising only mixed solvents were undertaken. With a sheath-to-core flow rate ratio of 0.2:1, the nanofibers prepared from the coaxial process had a smaller average diameter, narrower size distribution, more uniform structures, and smoother surface morphologies than those generated from single fluid electrospinning. In addition, the coaxial fibers provided a better zero-order drug release profile. The use of a sheath solvent means that the core jet is subjected to electrical drawing for a longer period, facilitating homogeneous core jet solidification and retarding the formation of wrinkles on the surface of the nanofibers. This modified coaxial electrospinning protocol allows the systematic fabrication of functional polymer nanofibers with improved quality.

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.

Solid lipid nanoparticles self-assembled from electrosprayed polymer-based microparticles

A new strategy for manipulating molecular self-assembly to produce solid lipid nanoparticles (SLNs) in situ is reported. Microparticulate composites (consisting of the polymer PVP, naproxen and tristearin as a lipophilic carrier) were prepared using an elevated temperature electrospraying process. Tristearin/naproxen SLNs formed spontaneously when the composite microparticles were placed into water, as a result of the PVP polymer matrix dissolving. The self-assembled SLNs had average diameter of 376 ± 20 nm, a drug entrapment efficiency of 86.2% and provided sustained drug release over 24 h, with 87.6% of the total NAP freed into the dissolution medium in this time. These findings open a new route for developing novel biomaterials and nanoparticulate drug delivery systems, and for resolving problems associated with the formulation of poorly water-soluble drugs.

Preparation of ultrafine fast-dissolving feruloyl-oleyl-glycerol-loaded polyvinylpyrrolidone fiber mats via electrospinning

Fast-dissolving drug delivery membranes for poorly water-soluble drugs were prepared by electrospinning using feruloyl-oleyl-glycerol (FOG) as a model drug and polyvinylpyrrolidone (PVP) K90 as a polymer matrix in a mixed solvent of chloroform/ethanol (4:1, v/v). Results from Fourier-transform infrared spectroscopy (FT-IR) illustrated good compatibility between FOG and PVP as well as a good distribution of FOG within the fibers. The morphology and diameter of the fibers were influenced by the concentration of PVP and the applied voltage. When the PVP concentration was 5% (w/v) and the applied voltage was 14 kV, uniform and smooth fibers were obtained, with diameter 700-800 nm. Wetting time assays confirmed fast-dissolving properties with the average dissolution time for FOG-loaded PVP fiber membranes being 2.0±1.5 s. These results demonstrate the potential of electrospinning solid dispersions to improve the dissolution profile of poorly water-soluble drugs.

A simple route to form magnetic chitosan nanoparticles from coaxial-electrospun composite nanofibers

Composite non-woven mats of poly(vinyl pyrrolidone) (PVP), chitosan, and Fe3O4 were successfully fabricated using coaxial-electrospinning technique with PVP/chitosan as the shell and PVP/Fe3O4 as the core. Because of the templating and confinement properties of the nanofibers, magnetic chitosan nanoparticles (MCNPs) could be spontaneously formed through molecular self-assembly when the composite fibers were dissolved on treatment with acetum solution. By changing the weight ratio of Fe3O4:chitosan, the size of the MCNPs could be varied. The morphology, chemical composition, and magnetic characteristics of composite particles were characterized by means of scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, and vibrating sample magnetometer. Experimental results indicated that the composite particles were super-paramagnetic with sizes in the range of 15–40xa0nm. This facile and new synthesis route comprises a convenient strategy to generate composite particles and should be broadly applicable to a wide range of systems, serving as a platform for the facile development of novel composite materials.

Metal chelate affinity precipitation: Purification of BSA using poly(N-vinylcaprolactam-co-methacrylic acid) copolymers

This investigation involves the metal chelate affinity precipitation of bovine serum albumin (BSA) using a copper ion loaded thermo-sensitive copolymer. The copolymer of N-vinylcaprolactam with methacrylic acid PNVCL-co-MAA was synthesized by free radical polymerization in aqueous solution, and Cu(II) ions were attached to provide affinity properties for BSA. A maximum loading of 48.1mg Cu(2+) per gram of polymer was attained. The influence of pH, temperature, BSA and NaCl concentrations on BSA precipitation and of pH, ethylenediaminetetraacetic acid (EDTA) and NaCl concentrations on elution were systematically probed. The optimum conditions for BSA precipitation occurred when pH, temperature and BSA concentration were 6.0, 10°C and 1.0 mg/ml, respectively and the most favorable elution conditions were at pH 4.0, with 0.2M NaCl and 0.06 M EDTA. The maximum amounts of BSA precipitation and elution were 37.5 and 33.7 mg BSA/g polymer, respectively. It proved possible to perform multiple precipitation/elution cycles with a minimal loss of polymer efficacy. The results show that PNVCL-co-MAA is a suitable matrix for the purification of target proteins from unfractionated materials.

Fabrication and aggregation of thermoresponsive glucose-functionalized double hydrophilic copolymers

Novel double-hydrophilic thermosensitive statistical glycopolymers, poly(N-isopropylacrylamide-co-6-O-vinyladipoyl-D-glucose), were fabricated using a chemoenzymatic process and free radical copolymerization. The structures of the glycopolymers were confirmed by (1)H and (13)C NMR, and their molar mass distributions determined by gel permeation chromatography. UV-vis spectroscopy data showed that the polymers exhibited reproducible temperature-responsive behavior. The self-assembly and critical aggregation concentration was verified by fluorescence spectroscopy with pyrene acting as a hydrophobic probe. Measurements by laser light scattering and transmission electron microscopy revealed that the glycopolymers were able to self-assemble into aggregates with varying particle sizes and morphologies in aqueous solutions.

A systematic study of captopril-loaded polyester fiber mats prepared by electrospinning.

In this study, drug-loaded nanofibers were prepared by electrospinning captopril (CPL) with aliphatic biodegradable polyesters. Poly(L-lactic acid) (PLLA), poly(lactic-co-glycolic acid) (PLGA), and poly(lactic-co-ε-caprolactone) (PLCL) were used as filament-forming matrix polymers, and the concentration of CPL in each fiber type was varied. Scanning electron microscopy indicated that the morphology and diameters of the fibers were influenced by the concentration of polymer in the spinning solution and the drug loading. CPL was found to be distributed in the polymer fibers in an amorphous manner using differential scanning calorimetry and X-ray diffraction. FTIR indicated that hydrogen bonding existed between the drug molecules and the carrier polymers. In vitro dissolution tests showed that drug release from the fibers was highly dependent on the release medium, temperature, and on the polymer used. A range of kinetic models were fitted to the drug-release data obtained, and indicated that release was diffusion controlled in all cases. The different polymer fibers have application in diverse areas of drug delivery, for instance as sub-lingual or sustained release systems. Furthermore, by combining different CPL-loaded fibers, it would be possible to produce a bespoke formulation with tailored drug-release properties.

The selective intercalation of organic carboxylates and sulfonates into hydroxy double salts

This paper reports the first systematic investigation of the selectivity of organic guest intercalation into hydroxy double salts. The organic guests 1,2- and 1,4-benzenedicarboxylate (1,2- and 1,4-BDC) have been incorporated into a range of hydroxy double salts by anion exchange. Intercalates of [Zn5(OH)8](NO3)2·yH2O, [Zn5(OH)8]Cl2·yH2O, [Zn5(OH)8](CH3COO)2·yH2O, [Zn3Ni2(OH)8](NO3)2·yH2O, and [Zn3.8Co1.2(OH)8](NO3)2·yH2O were prepared, and the resultant materials fully characterized. 1,5- and 2,6-Napthalanedisulfonate (1,5- and 2,6-NDS) were also successfully intercalated into the [Zn5(OH)8](NO3)2·yH2O material. It was found that the initial anions are almost completely replaced by the new organic guests in the majority of cases. Selected reactions were investigated by in situ X-ray diffraction, and the reactions observed to proceed directly from the host to the product largely under nucleation control. No intermediate phases were detected. The competitive intercalation of isomeric pairs of guest anions was explored, and very high degrees of preferential intercalation found for 1,4- over 1,2-BDC into all hydroxy double salts (HDSs) studied, and for 2,6- over 1,5-NDS into [Zn5(OH)8](NO3)2·yH2O. The selectivity was found to be largely invariant with reaction time, reaction temperature, solvent system, and guest concentration. It was also observed to be very similar across all the HDSs explored. In situ diffraction and NMR demonstrate that the selective intercalation is a thermodynamically controlled phenomenon. It is therefore suggested that preferential intercalation is governed in the main by the strength of the interactions between the HDS layers and the guest ions.

The first hydroxy double salt tablet formulation

For the first time, a hydroxy double salt containing an active pharmaceutical agent has been formulated into tablets. The tablets have excellent pharmaceutical properties and release the drug slowly over around 4 h when in conditions representative of the gastrointestinal tract.