Tranexamic acid loaded in a physically crosslinked trilaminate dressing for local hemorrhage control: Preparation, characterization, and in-vivo assessment using two different animal models.

This work aimed at formulating a trilaminate dressing loaded with tranexamic acid. It consisted of a layer of 3 % sodium hyaluronate to initiate hemostasis. It was followed by a mixed porous layer of 5 % polyvinyl alcohol and 2 % kappa-carrageenan. This layer acted as a drug reservoir that controlled its release. The third layer was 5 % ethyl cellulose backing layer for unidirectional release of tranexamic acid towards the wound. The 3 layers were physically crosslinked by hydrogen bonding as confirmed by Infrared spectroscopy. Swelling and release studies were performed, and results proposed that increasing number of layers decreased swelling properties and sustained release of tranexamic acid for 8 h. In vitro blood coagulation study was performed using human blood and showed that the dressing significantly decreased coagulation time by 70.5 % compared to the negative control. In vivo hemostatic activity was evaluated using tail amputation model in Wistar rats. Statistical analysis showed the dressing could stop bleeding in a punctured artery of the rat tail faster than the negative control by 59 %. Cranial bone defect model in New Zealand rabbits was performed to check for bone hemostasis and showed significant decrease in the hemostatic time by 80 % compared to the control.

Cost-effective and recyclable aerogels from cellulose acetate for oil spills clean-up.

Cigarette butts are the most known variety of anthropogenic litter on Earth, which consists mainly of cellulose acetate. It can be prepared as aerogel which can be used to remove oil pollution caused by heavy shipping traffic in the Baltic Sea. It is prepared as a solution in acetone which then is poured into water and oven-dried afterwards. The hydrophobicity can be simply improved by wetting with a little amount of oil. Aerogel's sorption capacity, as well as its regeneration for sorption of crude oil, marine diesel oil, and biodiesel sorption from water surface, has been estimated. Their recyclability to fresh samples with re-characterization has been also determined. It has been found that multiple use of cellulose acetate aerogels is not effective because the sorption capacity decreases by up to 80% after a single use. However, the sorption capacity of recycled samples decreases by only 20% on average compared to the samples from the first batch. This capacity could be fully exploited during the life cycle of cellulose acetate.

Hydrogel bioink based on clickable cellulose derivatives: Synthesis, characterization and in vitro assessment.

Hydrogel is considered as a promising candidate for bioink in terms of biocompatibility, biodegradability, printability and supporting cellular behavior. Recently, carbohydrates derivatives containing alkyne and azide pendant functional groups have been used in medical applications due to their improved chemical, biological, functional properties, and their amenability for chemical reactions under mild conditions. In this work, a novel bioink was developed based on azide and alkyne of cellulose derivatives. Azido-hydroxyethyl cellulose (D.Sazido = 0.04) was synthesized via open-ring reaction of 1-azido-2,3-epoxypropane and characterized spectroscopically and titrimetrically. Alkyne derivative, propargyl carboxymethyl cellulose (D.Spropargyl = 1.72) was synthesized through coupling reaction with propargylamine in the presence of EDC and NHS. The click-gel scaffold was obtained by mixing the two novel candidates in the presence of copper (I) catalyst. Extrusion bio-plotting experiment was successfully conducted of the two solutions into coagulant Cu (I)/DMSO solutions and demonstrated the possibility of using the clickable cellulose derivatives as bioink precursors. Chemical and physical properties of the click-gel were demonstrated. The biocompatibility assay of the prepared click-gels showed high level of viability in the human skin fibroblast cells (HFB4) at concentration 100 µg/mL.

Antibacterial and antioxidant assessment of cellulose acetate/polycaprolactone nanofibrous mats impregnated with propolis.

Cellulose acetate (CA) electrospun nanofibers are one of the most practical cellulosic material which normally applied as carriers for drug delivery and wound healing systems. In this study, CA and polycaprolactone (PCL) was applied to fabricate the electrospun nanofibrous for wound dressing application. Propolis is a resin-like macromolecule produced by honeybees from the buds and diverse plants. Among many applications of this macromolecule, it has been occasionally employed directly to the skin for wound healing applications. Herein, owing to the significance of propolis, CA/PCL nanofibers were impregnated with a propolis-extracted solution to reach antibacterial and antioxidant mat. The scanning electron microscopy (SEM) images revealed that electrospinning of 10% (w/w) CA along with 14% (w/w) PCL produced excellent nanofibers compared to the resultant nanofibers. Hydrophobicity/hydrophilicity nature of CA/PCL mats was measured using water contact-angle method before and after treatment with NaOH. The nanofibrous mats exhibited a high water absorption capacity of about 400%. Antioxidant effect was measured by 2,2-Diphenyl-1-picrylhydrazyl (DPPH) assay and propolis-CA/PCL presented a high antioxidant activity. Additionally, propolis-CA/PCL mats showed antibacterial activity against both the Gram-positive and Gram-negative bacteria. In conclusion, our results have confirmed that the propolis-impregnated CA/PCL mats have provided an appropriate surface for wound healing system.

Effect of aeration rate on the anti-biofouling properties of cellulose acetate nanocomposite membranes in a membrane bioreactor system for the treatment of pharmaceutical wastewater.

In this study, the effect of aeration rate in terms of specific aeration demand per membrane area (SADm) on the anti-biofouling properties of cellulose acetate (CA) nanocomposite membranes (CA/ND-NH2) in a membrane bioreactor system was investigated. The amount of EPS and soluble EPS under high aeration rate conditions was observed to be higher than under low aeration rate conditions. The results obtained showed that either lower or higher aeration rates had a negative impact on membrane permeability. The high aeration rate resulted in a severe breakage of sludge flocs, and promoted the release of soluble EPS from the microbial flocs to the bioreactor tank. By increasing the aeration rate, the COD removal increased and decreased respectively for the membranes and the activated sludge. It was finally concluded that higher anti-biofouling properties of neat CA and nanocomposite membranes were obtained under optimal aeration rate conditions (SADm = 1 m3 m-2 h-1).

Assessment of hot-processability and performance of ethylcellulose-based materials for injection-molded prolonged-release systems: An investigational approach.

The present work focuses on application of an investigational approach to assess the hot-processability of pharmaceutical-grade polymers with a potential for use in the manufacturing of reservoir drug delivery systems via micromolding, and the performance of resulting molded barriers. An inert thermoplastic polymer, ethylcellulose (EC), widely exploited for preparation of prolonged-release systems, was employed as a model component of the release-controlling barriers. Moldability studies were performed with plasticized EC, as such or in admixture with release modifiers, by the use of disk-shaped specimens ≥ 200 µm in thickness. The disks turned out to be a suitable tool for evaluation of the dimensional stability and diffusional barrier performance of the investigated materials after demolding. The effect of the amount of triethyl citrate, used as a plasticizer, on hot-processability of EC was assessed. The rate of a model drug diffusion across the polymeric barriers was shown to be influenced by the extent of porosity from the incorporated additives. The investigational approach proposed, of simple and rapid execution, holds potential for streamlining the development of prolonged-release systems produced by micromolding in the form of drug reservoirs, with no need for molds and molding processes to be set up on a case-by-case basis.

Industrial Development of a 3D-Printed Nutraceutical Delivery Platform in the Form of a Multicompartment HPC Capsule.

Following recent advances in nutrigenomics and nutrigenetics, as well as in view of the increasing use of nutraceuticals in combination with drug treatments, considerable attention is being directed to the composition, bioefficacy, and release performance of dietary supplements. Moreover, the interest in the possibility of having such products tailored to meet specific needs is fast growing among costumers. To fulfill these emerging market trends, 3D-printed capsular devices originally intended for conveyance and administration of drugs were proposed for delivery of dietary supplements. Being composed of separate inner compartments, such a device could yield customized combinations of substances, relevant doses, and release kinetics. In particular, the aim of this work was to face early-stage industrial development of the processes involved in fabrication of nutraceutical capsules for oral pulsatile delivery. A pilot plant for extrusion of filaments based on pharmaceutical-grade polymers and intended for 3D printing was set up, and studies aimed at demonstrating feasibility of fused deposition modeling in 3D printing of capsule shells according to Current Good Manufacturing Practices for dietary supplements were undertaken. In this respect, the stability of the starting material after hot processing and of the resulting items was investigated, and compliance of elemental and microbiological contaminants, as well as of by-products, with internal specifications was assessed. Finally, operating charts highlighting critical process variables and parameters that would serve as indices of both intermediate and final product quality were developed.

Structure/Function Analysis of Cotton-Based Peptide-Cellulose Conjugates: Spatiotemporal/Kinetic Assessment of Protease Aerogels Compared to Nanocrystalline and Paper Cellulose.

Nanocellulose has high specific surface area, hydration properties, and ease of derivatization to prepare protease sensors. A Human Neutrophil Elastase sensor designed with a nanocellulose aerogel transducer surface derived from cotton is compared with cotton filter paper, and nanocrystalline cellulose versions of the sensor. X-ray crystallography was employed along with Michaelis-Menten enzyme kinetics, and circular dichroism to contrast the structure/function relations of the peptide-cellulose conjugate conformation to enzyme/substrate binding and turnover rates. The nanocellulosic aerogel was found to have a cellulose II structure. The spatiotemporal relation of crystallite surface to peptide-cellulose conformation is discussed in light of observed enzyme kinetics. A higher substrate binding affinity (Km) of elastase was observed with the nanocellulose aerogel and nanocrystalline peptide-cellulose conjugates than with the solution-based elastase substrate. An increased Km observed for the nanocellulosic aerogel sensor yields a higher enzyme efficiency (kcat/Km), attributable to binding of the serine protease to the negatively charged cellulose surface. The effect of crystallite size and ß-turn peptide conformation are related to the peptide-cellulose kinetics. Models demonstrating the orientation of cellulose to peptide O6-hydroxymethyl rotamers of the conjugates at the surface of the cellulose crystal suggest the relative accessibility of the peptide-cellulose conjugates for enzyme active site binding.

Assessment of different polymers and drug loads for fused deposition modeling of drug loaded implants.

The 3D printing technique of fused deposition modeling® (FDM) has lately come into focus as a potential fabrication technique for pharmaceutical dosage forms and medical devices that allows the preparation of delivery systems with nearly any shape. This is particular promising for implants administered at application sites with a high anatomical variability where an individual shape adaption appears reasonable. In this work different polymers (Eudragit®RS, polycaprolactone (PCL), poly(l-lactide) (PLLA) and ethyl cellulose (EC)) were evaluated with respect to their suitability for FDM of drug loaded implants and their drug release behaviour was evaluated. The fluorescent dye quinine was used as a model drug to visualize drug distribution in filaments and implants. Quinine loaded filaments were produced by solvent casting and subsequent hot melt extrusion (HME) and model implants were printed as hollow cylinders using a standard FDM printer. Parameters were found at which model implants (hollow cylinders, outer diameter 4-5mm, height 3mm) could be produced from all tested polymers. The drug release which was examined by incubation of the printed implants in phosphate buffered saline solution (PBS) pH 7.4 was highly dependent on the used polymer. The fastest relative drug release of approximately 76% in 51days was observed for PCL and the lowest for Eudragit®RS and EC with less than 5% of quinine release in 78 and 100days, respectively. For PCL further filaments were prepared with different quinine loads ranging from 2.5% to 25% and thermal analysis proved the presence of a solid dispersion of quinine in the polymer for all tested concentrations. Increasing the drug load also increased the overall percentage of drug released to the medium since nearly the same absolute amount of quinine remained trapped in PCL at the end of drug release studies. This knowledge is valuable for future developments of printed implants with a desired drug release profile that might be controlled by the choice of the polymer and the drug load.

A Systematic Approach of Employing Quality by Design Principles: Risk Assessment and Design of Experiments to Demonstrate Process Understanding and Identify the Critical Process Parameters for Coating of the Ethylcellulose Pseudolatex Dispersion Using Non-Conventional Fluid Bed Process.

The goal of this study was to utilize risk assessment techniques and statistical design of experiments (DoE) to gain process understanding and to identify critical process parameters for the manufacture of controlled release multiparticulate beads using a novel disk-jet fluid bed technology. The material attributes and process parameters were systematically assessed using the Ishikawa fish bone diagram and failure mode and effect analysis (FMEA) risk assessment methods. The high risk attributes identified by the FMEA analysis were further explored using resolution V fractional factorial design. To gain an understanding of the processing parameters, a resolution V fractional factorial study was conducted. Using knowledge gained from the resolution V study, a resolution IV fractional factorial study was conducted; the purpose of this IV study was to identify the critical process parameters (CPP) that impact the critical quality attributes and understand the influence of these parameters on film formation. For both studies, the microclimate, atomization pressure, inlet air volume, product temperature (during spraying and curing), curing time, and percent solids in the coating solutions were studied. The responses evaluated were percent agglomeration, percent fines, percent yield, bead aspect ratio, median particle size diameter (d50), assay, and drug release rate. Pyrobuttons® were used to record real-time temperature and humidity changes in the fluid bed. The risk assessment methods and process analytical tools helped to understand the novel disk-jet technology and to systematically develop models of the coating process parameters like process efficiency and the extent of curing during the coating process.

Ethyl cellulose nanocarriers and nanocrystals differentially deliver dexamethasone into intact, tape-stripped or sodium lauryl sulfate-exposed ex vivo human skin - assessment by intradermal microdialysis and extraction from the different skin layers.

Understanding penetration not only in intact, but also in lesional skin with impaired skin barrier function is important, in order to explore the surplus value of nanoparticle-based drug delivery for anti-inflammatory dermatotherapy. Herein, short-term ex vivo cultures of (i) intact human skin, (ii) skin pretreated with tape-strippings and (iii) skin pre-exposed to sodium lauryl sulfate (SLS) were used to assess the penetration of dexamethasone (Dex). Intradermal microdialysis was utilized for up to 24h after drug application as commercial cream, nanocrystals or ethyl cellulose nanocarriers applied at the therapeutic concentration of 0.05%, respectively. In addition, Dex was assessed in culture media and extracts from stratum corneum, epidermis and dermis after 24h, and the results were compared to those in heat-separated split skin from studies in Franz diffusion cells. Providing fast drug release, nanocrystals significantly accelerated the penetration of Dex. In contrast to the application of cream and ethyl cellulose nanocarriers, Dex was already detectable in eluates after 6h when applying nanocrystals on intact skin. Disruption of the skin barrier further accelerated and enhanced the penetration. Encapsulation in ethyl cellulose nanocarriers delayed Dex penetration. Interestingly, for all formulations highly increased concentrations in the dialysate were observed in tape-stripped skin, whereas the extent of enhancement was less in SLS-exposed skin. The results were confirmed in tissue extracts and were in line with the predictions made by in vitro release studies and ex vivo Franz diffusion cell experiments. The use of 45kDa probes further enabled the collection of inflammatory cytokines. However, the estimation of glucocorticoid efficacy by Interleukin (IL)-6 and IL-8 analysis was limited due to the trauma induced by the probe insertion. Ex vivo intradermal microdialysis combined with culture media analysis provides an effective, skin-sparing method for preclinical assessment of novel drug delivery systems at therapeutic doses in models of diseased skin.

A membrane-based purification process for cell culture-derived influenza A virus.

A simple membrane-based purification process for cell culture-derived influenza virus was established that relies on only two chromatographic unit operations to achieve the contamination limits required according to regulatory authorities. After clarification and concentration, a pseudo-affinity membrane adsorber (sulfated cellulose, SCMA) was applied for virus capture. The subsequent polishing step consisted of a salt-tolerant anion exchange membrane adsorber (STMA) to bind residual DNA. For the presented process neither a buffer exchange step nor a nuclease step for further DNA digestion were required. As a starting point, a two-salt strategy (including a polyvalent ion) was employed to screen STMA conditions in a 96-well plate format. After optimization on chromatographic laboratory scale, the virus recovery was up to 97% with a residual DNA level below 0.82%. In addition, the STMA was characterized regarding its dynamic binding capacity and the impact of flow rate on yields and contamination levels. Overall, the total virus yield for influenza virus A/PR/8/34 (H1/N1) of this two-step membrane process was 75%, while the protein and the DNA contamination level could be reduced to 24% and at least 0.5%, respectively. With 19.8µg protein and 1.2ng DNA per monovalent dose, this purity level complies with the limits of the European Pharmacopeia for cell culture-derived vaccines for human use. Overall, the presented downstream process might serve as a generic and economic platform technology for production of cell culture-derived viruses and viral vectors.

In-vitro and in-vivo assessment of dextran-appended cellulose acetate phthalate nanoparticles for transdermal delivery of 5-fluorouracil.

The aim of this research was transdermal delivery of 5-fluorouracil (5-FU) using dextran-coated cellulose acetate phthalate (CAP) nanoparticulate formulation. CAP nanoparticles were prepared using drug-polymer ratio (1:1 to 1:3) and surfactant ratio (2.5, 5 and 10%). Dextran coating was made using aminodextran. The results showed that the optimized CAP nanoparticles (CNs) and dextran-coated CAP nanoparticles represented core-corona nanoparticles with the mean diameter of 75 ± 3 and 79 ± 2 nm, respectively, and entrapment efficiency was 82.5 ± 0.06 and 78.2 ± 0.12, respectively. Dextran-coated nanoparticles (FDCNs) and CAP nanoparticles (FCNs) showed in vitro 5-FU release upto 31 h and 8 h, respectively. Moreover, the cumulative amount of 5-FU penetrated through excised skin from FDCNs was 2.94 folds than that of the FU cream. Concentration of 5-FU in epidermis and dermis were also studied. In dermis, concentration of 5-FU was found higher in case of FDCN formulation than plain FU cream. FDCNs were found more hemocompatible in comparison to FCNs. The hematological data recommended that FDCNs formulation was less immunogenic compared to FU creams formulation. In blood level study, FDCNs exhibited 153, 12, 16.66 and 16.24-fold higher values for area under the curve, Tmax, Cmax and mean residence time (MRT) compared with those of FU cream, respectively. The in-vitro cytotoxicity was assessed using the MCF-7 by the MTT test and was compared to the plain 5-FU solution. All the detailed evidence showed that FDCNs could provide a promising tuning as a transdermal delivery system of 5-FU.

A comparison of hysterosalpingo-foam sonography (HyFoSy) and hysterosalpingo-contrast sonography with saline medium (HyCoSy) in the assessment of tubal patency.

OBJECTIVE: A randomized controlled selective cross-over trial was performed to compare the diagnostic yield and efficacy of ExEm foam (HyFoSy) with saline medium (HyCoSy) as a contrast agent for hysterosalping-contrast sonography in subfertile patients. STUDY DESIGN: 40 patients were randomized into HyCoSy with saline medium and HyFoSy with ExEm foam. Tubal patency were assessed according to pre-determined objective criteria that classified tubes based on degree of certainty in tubal patency. Selective cross-over testing with the other medium was performed in patients who had at least one possibly occluded or unexaminable tube on the initial test. RESULTS: 80 tubes were evaluated. On initial testing, the proportion of tubes that were classified as patent was higher with HyFoSy compared to HyCoSy (70.0% vs 40.0%, p=0.01). A higher proportion of patients in the HyCoSy group required crossover testing [80.0% (16/20) vs 45.0% (9/20), p=0.02]. On cross-over testing, 41.7% (10/24) of possibly occluded or unexaminable tubes in the HyCoSy group were re-classified as patent when examined with Ex-Em foam, compared to 8.3% (1/12) of possibly occluded or unexaminable tubes in the HyFoSy group (p=0.03). CONCLUSION: ExEm foam medium (HyFoSy) might improve the diagnostic yield and efficacy over saline medium (HyCoSy) for hysterosalpingsonography.

In-line coupling of microextractions across polymer inclusion membranes to capillary zone electrophoresis for rapid determination of formate in blood samples.

Polymer inclusion membranes (PIMs) have several important features, i.e., PIMs are dry and non-porous membranes, which can be prepared ahead of use and stored without noticeable deterioration in extraction performance. In this contribution, in-line coupling of microextractions across PIMs to a separation method for clinical purposes was demonstrated for the first time. Formate (the major metabolite in methanol poisoning) was determined in undiluted human serum and whole blood by capillary zone electrophoresis (CZE) with simultaneous capacitively coupled contactless conductivity detection (C(4)D) and UV-Vis detection. A purpose-made microextraction device with PIM was coupled to a commercial CZE instrument in order to ensure complete automation of the entire analytical procedure, i.e., of formate extraction, injection, CZE separation and quantification. PIMs for formate extractions consisted of 60% (w/w) cellulose triacetate as base polymer and 40% (w/w) Aliquat™ 336 as anion carrier. The method was characterized by good repeatability of peak areas (≤7.0%) and migration times (≤0.8%) and by good linearity of calibration curves (r(2) = 0.993-0.999). Limits of detection in various matrices ranged from 15 to 54 µM for C(4)D and from 200 to 635 µM for UV-Vis detection and were sufficiently low to clearly distinguish between endogenous and toxic levels of formate in healthy and methanol intoxicated individuals. In addition, PIMs proved that they may act as phase interfaces with excellent long-term stability since once prepared, they retained their extractions properties for, at least, two months of storage.

Real-time assessment of granule densification in high shear wet granulation and application to scale-up of a placebo and a brivanib alaninate formulation.

Real-time monitoring and control of high shear wet granulation (HSWG) using process analytical technologies is crucial to process design, scale-up, and reproducible manufacture. Although significant progress has been made in real-time measurement of granule size distribution using focused beam reflectance measurement (FBRM), real-time in-line assessment of granule densification remains challenging. In this study, a drag force flow (DFF) sensor was developed and used to probe wet mass consistency in real-time. In addition, responses from FBRM and DFF sensors were compared to assess complementarity of information on granulation progress from the two probes. A placebo and a brivanib alaninate formulation were granulated with different concentrations of binder or water, respectively, while measuring granule size growth, densification, and DFF sensor response. The DFF sensor was able to quantitatively characterize with high resolution a response of wet mass consistency distinct from granule size distribution. The wet mass consistency parameter correlated well with granule densification, which was shown as a critical material attribute that correlated with tablet dissolution. In addition, application of DFF sensor to scale-up of granulation was demonstrated. These results showed the value of wet mass consistency measurement using DFF for WG monitoring and control.

Influence of binder droplet dimension on granulation rate during fluidized bed granulation.

Here, we statistically identified the critical factor of the granulation rate during the fluidized bed granulation process. Lactose was selected as the excipient and was granulated with several binders, including hydroxypropyl cellulose, hydroxypropyl methyl cellulose, and polyvinylpyrrolidone. The viscosity, density, and surface tension of the binder solution, contact angle, and the work done during adhesion and cohesion between the binder and lactose, mist diameter, Stokes number, and the dimension of the droplet were considered. The Stokes number was defined as the ratio of the inertial force to the viscous-damping force of a particle. We confirmed that droplet diameter after adhesion had the highest correlation coefficient with the granulation rate constant in our investigated parameters. Partial least squares regression revealed two critical principal components of the granulation rate: one relating to the droplet dimension, which is composed of mist diameter and diameter and thickness of the droplet after adhesion of the binder to the lactose surface; and the other relating to wettability, which involves the work done during adhesion and cohesion, surface tension, and the thickness of the droplet after adhesion of the binder to the lactose surface.

Facile preparation of polysaccharide-coated capillaries using a room temperature ionic liquid for chiral separations.

In this study, the dissolution of polysaccharides into an ionic liquid was investigated and applied as a coating onto the capillary walls of a fused-silica capillary in open-tubular CEC. The coating was evaluated by examining the chiral separation of two analytes (thiopental, sotalol) with three cellulose derivatives (cellulose acetate, cellulose acetate phthalate, and cellulose acetate butyrate). Baseline separation of thiopental enantiomers was achieved by use of each polysaccharide coating (Rs: 7.0, 8.1, 7.1), while sotalol provided partial resolution (Rs: 0.7, 1.0, 0.9). In addition, reproducibility of the cellulose-coated capillaries was evaluated by estimating the run-to-run and capillary-to-capillary RSD values of the EOF. Both stability and reproducibility were very good with RSD values of less than 7%.

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.