Dilyana Paneva

Preparation of chitosan-containing nanofibres by electrospinning of chitosan/poly(ethylene oxide) blend solutions

Abstract The first successful preparation of chitosan-containing nanofibres was achieved by electrospinning of chitosan/poly(ethylene oxide) (PEO) blend aqueous solutions. The diameters of the nanofibres were in the range 40 - 290 nm and decreased with increasing chitosan content and decreasing total concentration. An increase of the applied field strength leads to an increase of the diameter of the nanofibres and to a broadening of the size distribution. The possibility to prepare nanofibres containing a model drug - potassium 5-nitro-8-quinolinolate (K5N8Q), a broad-spectrum antimicrobial and antimycotic agent - was shown. The incorporation of K5N8Q in the nanofibres resulted in a decrease of the nanofibre diameters and the appearance of bead-shaped defects. Non-woven mats from the drugloaded nanofibres with composition chitosan : PEO = 1:1 (w/w) and 1% K5N8Q showed antibacterial and antimycotic activity against E. coli, S. aureus and C.albicans.

Perspectives On: Criteria for Complex Evaluation of the Morphology and Alignment of Electrospun Polymer Nanofibers

Electrospinning is a promising method for producing polymer materials composed of micro- and nanosized fibers. This method allows the preparation of random and aligned fibers of different morphologies, such as cylindrical or ribbon-shapes, defect-free or with defects, and with or without pores or porous. The increasing number of studies on electrospinning requires a set of criteria for more complex evaluation of the fiber morphology and the topology of these polymer materials to be established. The main characteristics necessary for a complex evaluation of the morphology of electrospun micro- and nanofibers have been systematized in this paper. Examples of characterization of the morphology and of the alignment of various micro- and nanofibers are given.

Polylactide Stereocomplex-Based Electrospun Materials Possessing Surface with Antibacterial and Hemostatic Properties

Novel fibrous materials of stereocomplex between high-molecular-weight poly(d- or l-)lactide (HMPDLA or HMPLLA) and diblock copolymers consisting of poly(l- or d-)lactide and poly(N,N-dimethylamino-2-ethyl methacrylate) blocks, respectively (PLLA-block-PDMAEMA or PDLA-block-PDMAEMA), were prepared by solution electrospinning. Fibers with mean diameters ranging from 1400 to 1700 nm were obtained. The stereocomplex formation was evidenced by differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analyses. Annealing at 100 degrees C for 8 h resulted in the appearance of crystalline peaks at 2theta values of 12, 21, and 24 degrees for PLA stereocomplex. X-ray photoelectron spectroscopy (XPS) analyses revealed the gradient composition of the fibers with a surface enriched in tertiary amino groups from PDMAEMA blocks. The availability of tertiary amino groups imparts hemostatic and antibacterial properties to the stereocomplex fibrous materials, as indicated by the performed tests on blood cells and on pathogenic microorganisms.

Amphiphilic poly(D- or L-lactide)-b-poly(N,N-dimethylamino-2-ethyl methacrylate) block copolymers: controlled synthesis, characterization, and stereocomplex formation.

Novel well-defined amphiphilic poly(D-lactide)-b-poly(N,N-dimethylamino-2-ethyl methacrylate) (PDLA-b-PDMAEMA) and poly(L-lactide)-b-poly(N,N-dimethylamino-2-ethyl methacrylate) (PLLA-b-PDMAEMA) copolymers were obtained. The synthesis strategy consisted of a three-step procedure: (i) controlled ring-opening polymerization (ROP) of (D- or L-)lactide initiated by Al(O(i)Pr)(3), followed by (ii) quantitative conversion of the polylactide (PLA) hydroxyl end-groups with bromoisobutyryl bromide and (iii) atom transfer radical polymerization (ATRP) of DMAEMA. The PLA block molecular weight was kept below 5000 g/mol. The macromolecular parameters of the (co)polymers were determined by (1)H NMR spectroscopy and size exclusion chromatography (SEC). The stereocomplexes of PDLA-b-PDMAEMA/PLLA-b-PDMAEMA diblock copolymers were prepared via solvent casting. The stereocomplex formation was evidenced by differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analyses. The obtained stereocomplexes had melting temperature of about 65 degrees C above that of the individual copolymers and exhibited diffraction patterns assigned to the stereocomplex crystallites. In addition, for the first time it was shown that the replacement of one of the PLA partners with high molecular weight PLLA or PDLA did not hamper the stereocomplex formation. The presence of PDMAEMA blocks proved to impart hydrophilicity of the synthesized copolymers and related stereocomplexes, as determined by static water contact angle measurements.

Preparation of Polyelectrolyte-Containing Nanofibers by Electrospinning in the Presence of a Non-Ionogenic Water-Soluble Polymer

The first successful preparation of nanofibers of a polyampholyte (N-carboxyethylchitosan) by electrospinning was achieved by adding a non-ionogenic water-soluble polymer to the spinning solution. Using this approach, other polyelectrolytes, poly(2-acryloylamido-2-methylpropanesulphonic acid) (PAMPS), and copolymers of 2-acryloylamido-2-methylpropane-sulphonic acid (AMPS) and acrylic acid [P(AMPS-co-AA)] were also electrospun into nanofibers. The non-ionogenic water-soluble polymers were polyacrylamide (PAAm) and poly(vinyl alcohol) (PVA). The average diameters of the electrospun nanofibers were in the range 50-260nm. The average diameter of the nanofibers significantly decreased with increasing polyelectrolyte content. The electrospun nanofibers were crosslinked by heat treatment at 100, 120 or 150°C for the N-carboxyethylchitosan/PAAm pair and at 90°C in the case of P(AMPS-co-AA)/PVA. The presence of an ionizable low-molecular-weight compound (7-iodo-8-hydroxyquinoline-5-sulphonic acid, SQ) led to a more than two-fold decrease in the diameter of the nanofibers and to the appearance of defects. The SQ-containing nanofibers showed antimicrobial activity against pathogenic microorganisms.

Hybrid nanofibrous yarns based on N-carboxyethylchitosan and silver nanoparticles with antibacterial activity prepared by self-bundling electrospinning.

Hybrid nanofibrous materials with antibacterial activity consisting of yarns from N-carboxyethylchitosan (CECh) and poly(ethylene oxide) (PEO) that contain 5 wt% or 10 wt% silver nanoparticles (AgNPs) were prepared. This was achieved by electrospinning using formic acid as a solvent and as a reducing agent for silver ions. AgNO₃ was used as an Ag(+)-containing salt. Its concentration was selected to be 0.02 mol/L or 0.04 mol/L in order the content of the AgNPs in the electrospun nanofibers to be 5 wt% or 10 wt%, respectively. The self-bundling of the fibers into yarns with a mean diameter of ca. 35 μm was enabled only by using a grounded needle electrode. The reduction of the silver ions to an elemental silver was evidenced by UV-vis spectroscopy, X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). The transmission electron microscopy (TEM) analyses revealed that AgNPs formed at AgNO₃ concentration of 0.02 mol/L were with a mean diameter of 4±0.5 nm and were distributed uniformly within the fiber. The increase of AgNO₃ concentration to 0.04 mol/L led to the preparation of AgNPs with a higher mean diameter and a broader diameter distribution as well as to aggregate formation. The performed studies on the antibacterial activity of CECh/PEO/AgNPs fibrous materials against Staphylococcus aureus showed that at AgNPs content of 5 wt% the mats had bacteriostatic, and at AgNPs content of 10 wt%-bactericidal activity.

Antibacterial fluoroquinolone antibiotic-containing fibrous materials from poly(L-lactide-co-D,L-lactide) prepared by electrospinning.

Microfibrous materials based on poly(l-lactide-co-d,l-lactide) (coPLA) and coPLA/poly(ethylene glycol) (PEG) containing a fluoroquinolone antibiotic: ciprofloxacin hydrochloride (Cipro), levofloxacin hemihydrate (Levo) or moxifloxacin hydrochloride (Moxi) were obtained by electrospinning. The presence of Moxi led to an increase in the conductivity of the coPLA and coPLA/PEG spinning solutions and to the preparation of membranes composed of fibers aligned with the collector rotation direction. The one-step incorporation of the antibiotics in the fibers was confirmed by infrared spectroscopy and fluorescence microscopy. The antibiotics were dispersed in the coPLA or coPLA/PEG polymer matrix and the XRD spectra revealed the presence of crystalline phase characteristic of PEG and of the respective antibiotic. It was found that the release profiles of the antibiotics did not depend on the antibiotic nature but were dependent on the fiber composition. The presence of PEG in the fibers allowed a more rapid antibiotic release within the first 2h of release. The performed microbiological tests with Staphylococcus aureus revealed that the coPLA/Cipro, coPLA/PEG/Cipro, coPLA/Levo, coPLA/PEG/Levo, coPLA/Moxi and coPLA/PEG/Moxi mats inhibited the bacterial growth. In addition, the presence of an antibiotic in the mats led to a substantial decrease in the adhesion of the pathogenic microorganism and in the case of the coPLA/PEG/antibiotic series - to prevention thereof.

Electrospun Hybrid Nanofibers Based on Chitosan or N‐Carboxyethylchitosan and Silver Nanoparticles

Hybrid nanofibers from chitosan or N-carboxyethylchitosan (CECh) and silver nanoparticles (AgNPs) were prepared by electrospinning using HCOOH as a solvent. AgNPs were synthesized in situ in the spinning solution. HCOOH slowed down the cross-linking of the polysaccharides with GA enabling the reactive electrospinning in the presence of poly(ethylene oxide) (PEO). EDX analyses showed that AgNPs are uniformly dispersed in the nanofibers. Since AgNPs hampered the cross-linking of chitosan and CECh with GA in the hybrid fibers, the imparting of water insolubility to the fibers was achieved at a second stage using GA vapors. The surface of chitosan/PEO/AgNPs nanofibers was enriched in chitosan and 15 wt.-% of the incorporated AgNPs were on the fiber surface as evidenced by XPS.

Polylactide (PLA)-Based Electrospun Fibrous Materials Containing Ionic Drugs as Wound Dressing Materials: A Review

The effect of the electrospinning process parameters on the morphology, alignment, and self-organization of the fibers into bundles and/or yarns are outlined. The fabrication of polylactide materials containing ionic drugs by electrospinning is emphasized. The main approaches used for the preparation of electrospun drug-loaded materials: electrospinning of a mixed solution containing the polymer(s) and the drug(s) or dual spinneret electrospinning of separate drug-containing solutions are compared. The latter approach allows the obtaining of drug-loaded fibrous materials while avoiding the drug interaction. The potential application of the obtained materials containing ionic drugs as wound dressings is outlined.

Drug-loaded electrospun polylactide bundles:

Bundle membranes were made by electrospinning poly(L-lactide) (PLLA) and PLLA/poly(ethylene glycol) (PEG) using the ionic properties of diclofenac sodium (DS), lidocaine hydrochloride (LHC), benzalkonium chloride (BC), and combinations thereof. The self-bundling of the fibers was initiated by using a designed grounded multi-needle electrode. Computer simulations on the electrostatic field distribution depended on the multi-needle position with respect to a grounded rotating drum collector which allowed the optimal arrangement of the electrospinning component set-up to obtain bundles. The combination of the ionization of the drugs as well as the utilization of the multi-needle electrode allowed the successful preparation of a series of mono-(DS, LHC, or BC), bi-(DS/LHC), and three-(DS/LHC/BC) drug(s)-loaded bundle membranes. Based on the Fourier transform infrared spectra, the drug systems were incorporated into the fibrous materials. The microbiological tests confirmed that the PLLA/ PEG bundle membranes containing BC (10 wt%), DS (30 wt%), DS/LHC (DS, 30 wt%; LHC, 30 wt%), and DS/LHC/BC (DS, 15 wt%; LHC, 15 wt%; and BC, 10 wt%) exhibited antibacterial activity against the pathogenic microorganism Staphylococcus aureus.