Low Polymer Concentrations Research Articles

A supramolecular host-guest interaction-mediated injectable hydrogel system with enhanced stability and sustained protein release

Injectable hydrogels have been studied as drug delivery systems because of their minimal invasiveness and sustained drug release properties. Pluronic F127, consisting of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) triblock copolymers, exhibits thermo-responsive properties and hence is injectable due to its rapid sol-gel transition. Unmodified Pluronic F127-based hydrogels, however, have limited long-term stability and controllable release of drugs entrapped within them. In this study, host-guest interactions between adamantane-conjugated Pluronic F127 (F127-Ad) and polymerized β-cyclodextrin (CDP) were employed to develop a hydrogel-based protein delivery system. Single or multiple adamantane units were successfully introduced at the termini of Pluronic F127 with a 100% conversion yield, and the synthesized F127-Ad polymer produced a physically crosslinked micelle-packing structure when mixed with CDP. As the number of adamantanes at the terminal ends of Pluronic F127 increased, the critical gelation concentration of F127-Ad/CDP hydrogel decreased from 15 to 6% (w/v). The F127/CDP hydrogel was able to maintain its structure even with lower polymer content, and its injectability improved with a reduction of the hydrogel viscosity. The long-term stability of F127/CDP hydrogels was evaluated in vitro and in vivo, and it was demonstrated that the subcutaneously injected hydrogel did not disintegrate for up to 30 d. Throughout the drug release test using gelatin and insulin as model drugs, it was demonstrated that their release rates could be regulated via complexation between the protein drugs and the β-cyclodextrin molecules inside the hydrogel. In conclusion, the F127-Ad/CDP hydrogel is expected to be a versatile protein delivery system with controllable durability and drug release characteristics. Statement of significancePluronic F127 is one of the widely studied polymeric materials for thermo-sensitive injectable hydrogels due to its high biocompatibility and rapid sol-gel transition. Since the Pluronic F127-based hydrogel has some limitations in its long-term stability and mechanical property, it is inevitable to modify its structure for the application to drug delivery. In this study, mono- or multi- adamantane-conjugated Pluronic F127s were synthesized and mixed with β-cyclodextrin polymers to form hydrogels with host-guest interaction-mediated micelle-packing structures. The host-guest interaction introduced into the hydrogel system endowed it a sustained protein drug release behavior as well as high durability in vitro and in vivo. By increasing the number of adamantane molecules at the end of the Pluronic F127, both the stability and injectability of the hydrogel could be also modulated.

Efficacy of two natural tannins-based polymers in contrast to aluminum sulfate for drinking water production

Abstract The rapid population growth requires significantly increase of the water treatment rates with high efficiencies, larger amounts of aluminum sulfate, and higher volumes of both sludge and filter backwash water and increased of the treatment costs. It believed that replacing the aluminum sulfate for natural polymers is an alternative to improve the treatments and reduce risks related to the presence of aluminum ions in the processes of water production. In this study, raw water from a drinking water treatment company at southern Brazil were assessed in terms of treatment with two natural tannins-based polymers in contrast to a conventional aluminum sulfate (the classical metal salt for water clarification). Jar test studies were performed to removal of turbidity and color. The main results showed that low polymer concentration (15 ​mg/L) allowed up to 90% turbidity removal and 86% color removal. In addition, alkalinity, pH, electrical conductivity and organic matter content was not increased. If compared, the tannins-based polymers could replace the aluminum sulfate. Thus, it believed that this work contribute to research in the area of natural polymers to promote high clarification efficiencies and safety for health and environment.

Microfluidic 3D Printing of a Photo-Cross-Linkable Bioink Using Insights from Computational Modeling.

Three-dimensional (3D) bioprinting of photo-cross-linkable hydrogel precursors has attracted great interest in various tissue engineering and drug screening applications, as the biochemical and biophysical properties of the resultant hydrogel structures can be tuned spatiotemporally to provide cells with physiologically relevant microenvironments. In particular, these bioinks benefit from great biofunctional versatility that can be designed to direct cells toward a desired behavior. Despite significant progress in the field, the 3D printing of cell-laden photo-cross-linkable bioinks with low polymer concentrations has remained a challenge, as rapidly stabilizing these bioinks and transforming them to hydrogel filaments is hindered by their low viscosity. Additionally, reaching an optimized print condition has often been challenging due to the large number of print parameters involved in 3D bioprinting setups. Therefore, computational modeling has occasionally been employed to understand the impact of various print parameters and reduce the time and resources required to determine these effects in experimental settings. Here, we report a novel 3D bioprinting strategy for fabricating hydrogel fibrous structures of gelatin methacryloyl (GelMA) with superior control over polymer concentration, particularly in a relatively low range from ∼1% (w/v) to 6% (w/v), using a microfluidic printhead. The printhead features a coaxial core-sheath flow, coupled with a photo-cross-linking system, allowing for the in situ cross-linking of GelMA and the generation of hydrogel filaments. A computational model was developed to determine the optimal ranges of process parameters and inform about the diffusive and fluid dynamic behavior of the coaxial flow. The cytocompatibility of the biofabrication system was determined via bioprinting cell-laden bioinks containing U87-MG cells. Notably, the established pipeline from computational modeling to bioprinting has great potential to be applied to a wide range of photo-cross-linkable bioinks to generate living tissues with various material and cellular characteristics.

Modeling elongational viscosity and brittle fracture of polystyrene solutions

Elongational viscosity data of well-characterized solutions of 3–50% weight fraction of monodisperse polystyrene PS-820k (molar mass of 820,000 g/mol) dissolved in oligomeric styrene OS8.8 (molar mass of 8800 g/mol) as reported by André et al. (Macromolecules 54:2797–2810, 2021) are analyzed by the Extended Interchain Pressure (EIP) model including the effects of finite chain extensibility. Excellent agreement between experimental data and model predictions is obtained, based exclusively on the linear-viscoelastic characterization of the polymer solutions. The data were obtained by a filament stretching rheometer, and at high strain rates and lower polymer concentrations, the stretched filaments fail by rupture before reaching the steady-state elongational viscosity. Filament rupture is predicted by a criterion for brittle fracture of entangled polymer liquids, which assumes that fracture is caused by scission of primary C-C bonds of polymer chains when the strain energy reaches the bond-dissociation energy of the covalent bond (Wagner et al., J. Rheology 65:311–324, 2021).

Intense Quench Process in Slow Agitated Water Salt and Polymer Solutions

In the paper it is shown that quenching in slow agitated water salt solution of optimal concentration and in low concentration of inverse solubility polymers is intensive quenching creating maximal temperature gradients at the beginning of cooling. The evidence to support such idea were collected by analyzing quenching process in liquid media where any film boiling process was completely absent. In this case, surface temperature at the beginning of cooling drops closely to saturations temperature of a liquid within the interval 1–2 seconds, independently on nature of water solution, and then during transient nucleate boiling process maintains at the level of boiling point of a liquid which is often called self–regulated thermal process. The computer modeling of such cooling processes provided Kondrat’ev numbered Kn which are strongly linear function of time. At the beginning of cooling Kondrat’ev number is almost equal to 1 while average Kondrat’ev number Kn≥0.8. According to US Patent, intensive quenching starts when Kn=0.8. Based on achieved results, it is possible to perform intensive quenching in slow agitated of low concentration water salt and polymer solutions, usually initiated by hydrodynamic emitters. Along with liquid agitation, emitters generate resonance wave effect which destroys film boiling processes making cooling very uniform and intensive. The proposed IQ process works perfectly when martensite starts temperature Ms>Ts. If saturation temperature Ts≥Ms, intensive austempering process via cold liquids can be successfully performed to replace slow cooling of molten salts and alkalis by intensive quenching in liquid media.

Tyrosol Derived Poly(ester-arylate)s for Sustained Drug Delivery from Microparticles

New biodegradable polymers are needed for use in drug delivery systems to overcome the high burst release, lack of sustained drug release, and acidic degradation products frequently observed in current formulations. Commercially available poly(lactide-co-glycolide) (PLGA) is often used for particle drug release formulations; however, it is often limited by its large burst release and acidic degradation products. Therefore, a biocompatible and biodegradable tyrosol-derived poly(ester-arylate) library has been used to prepare a microparticle drug delivery system which shows sustained delivery of hydrophobic drugs. Studies were performed using polymers with varying hydrophilicity and thermal properties and compared to PLGA. Various drug solubilizing cosolvents were used to load model drugs curcumin, dexamethasone, nicotinamide, and acyclovir. Hydrophobic drugs curcumin and dexamethasone were successfully loaded up to 50 weight percent (wt %), and a linear correlation between drug wt % loaded and the particle glass transition temperature (Tg) was observed. Both curcumin and dexamethasone were visible on the particle surface at 20 wt % loading and higher. By adjusting the polymer concentration during particle formation, release rates were able to be controlled. Release studies of dexamethasone loaded particles with a lower polymer concentration showed a biphasic release profile and complete release after 47 days. Particles prepared using a higher polymer concentration showed sustained release for up to 77 days. Comparably, PLGA showed a traditional triphasic release profile and complete release after 63 days. This novel tyrosol-derived poly(ester-arylate) library can be used to develop injectable, long-term release formulations capable of providing sustained drug delivery.

Phase stability of colloidal spheres mixed with supramolecular rod‐like polymers

AbstractMixtures of colloids and supramolecular polymers exhibit stimuli‐responsive phase behavior. In previous work (Peters and Tuinier, Physica A 510, 233 [2018]) the polymers were treated as fully flexible chains, while in experimental systems supramolecular polymers may have a certain degree of stiffness. Here we predict that for stiff rod‐like supramolecular polymers phase separation can occur at much lower polymer concentrations than for flexible supramolecular polymers. Additionally, it is demonstrated that colloid–polymer interactions can significantly influence the equilibrium polymer size distribution, however this does not strongly affect the phase behavior of the mixture. At the low polymer concentrations at which the system already gets unstable, the effect of excluded volume interactions between polymers chains themselves is small. Finally, for an experimental system it is predicted that a variety of re‐entrant phase transitions may be observed within a realistic temperature range as illustrated by a specific example.

A Monte Carlo simulation of water + oil + ABA block copolymer ternary system. I. Patterns in thermal equilibrium

We carried out a large-scale lattice Monte Carlo simulation of a ternary system comprising water/oil/ABA triblock copolymers with hydrophilic A and hydrophobic B blocks to investigate the dependence of the pattern on the volume fraction of the components. The attractive interaction energies due to hydrogen bonding between the hydrophilic A block and water and between waters were defined as the relative values to the van der Waals bonding between water and oil. We created a phase diagram at thermal equilibrium. At low polymer concentrations, the water and oil were perfectly immiscible. As the polymer concentration increased, the pattern changed from one characterized by macro-phase separation to one characterized by micro-domain structures. At intermediate polymer concentrations, the pattern changed from water-in-oil micellar to lamellar to layer–passage structures as the water concentration increased. A bicontinuous pattern emerged when the concentrations of the polymer and water were the greatest. At low water concentrations, micelles formed at various copolymer concentrations. These pattern changes were approximately and qualitatively similar to those of pre-existing experimental phase diagrams of water/oil/ABA block copolymers. In our model, the lamellar structure comprised a lipid bilayer, and the area where ordered structures such as lamella appeared was limited to the narrow area of the phase diagram. The formation of ordered structures was due to the confinement of the system by the parallel walls and depended on the choice of a suitable ratio of the three components and the appropriate polymer length to produce ordered patterns commensurate with the distance between the walls.

An Advanced Material with Synergistic Viscoelasticity Enhancement of Hydrophobically Associated Water‐Soluble Polymer and Surfactant

In order to prepare materials with controllable properties, changeable microstructure, and high viscoelasticity solution with low polymer and surfactant concentration, a composite is constituted by adding surfactant (sodium dodecyl sulfate, SDS) to hydrophobically associated water-soluble polymer (abbreviated as PAAC) solution. The viscoelasticity, aggregate microstructure, and interaction mechanism of the composite are investigated by rheometery, Cryo-transmission electron microscopy (Cryo-TEM), and fluorescence spectrum. The results show that when the mass ratio of polymer to surfactant is 15:1, the viscosity of the composite reaches the maximum. The viscosity of the composite system increases hundredfold. The viscosity plateau under dynamic shear is generated. The composite has the properties of high viscoelasticity, strong shear thinning behavior, and good salt tolerance, and temperature resistance. The maximum viscosity of the composite is shown at the salinity of 20000mg L-1 . In addition, there is no phase separation in the composite with the increase of polymer and surfactant concentration, which indicates the good stability of the system. It is proposed a method to obtain a high viscoelasticity solution by adding surfactants without wormlike micelles to a hydrophobically associated water-soluble polymer solution.

Dynamic Subsurface Deformation and Strain of Soft Hydrogel Interfaces Using an Embedded Speckle Pattern With 2D Digital Image Correlation

Subsurface mechanisms can greatly affect the mechanical behavior of biological materials, but observation of these mechanisms has remained elusive primarily due to unfavorable optical characteristics. Researchers attempt to overcome these limitations by performing experiments in biological mimics like hydrogels, but measurements are generally restricted due to the spatio-temporal limitations of current methods. Utilization of contemporary 3D printing techniques into soft, transparent, aqueous yield-stress materials have opened new avenues of approach to overcoming these roadblocks. By incorporating digital image correlation with such 3D printing techniques, a method is shown here that can acquire full-field deformation of a hydrogel subsurface in real-time. Briefly, the method replaces the solvent of a transparent and low polymer concentration yield-stress material with an aqueous hydrogel precursor solution, then a DIC speckle plane is 3D printed into it. This complex is then polymerized using photoinitiation thereby locking the speckle plane in place. Full-field deformation measurements are made in real-time as the embedded speckle plane (ESP) responds with the bulk to the applied load. Example results of deformation and strain fields associated with indentation, relaxation, and sliding contact experiments are shown. This method has successfully observed the subsurface mechanical response in the bulk of a hydrogel and has the potential to answer fundamental questions regarding biological material mechanical behaviors.

Polymers for aluminium secondary batteries: Solubility, ionogel formation and chloroaluminate speciation

This work deals with the search of polymers apt for the preparation of solid-like chloroaluminate-based electrolytes. To accomplish this, the solubility and gelling ability of a large set of polymers in the deep eutectic solvent AlCl3:urea (uralumina) are studied, followed by the characterization of the electrochemical activity of the gels. The polymers are directly dissolved in urea:AlCl3 without auxiliary solvents following a fast and scalable gel preparation methodology previously reported for ultra-high molecular weight (UHMW) polyethylene oxide (PEO). The list of polymers studied includes diverse chemical structures, different thermal properties and different aggregation states at the mixing temperature of 70 °C, defined by the thermal stability of AlCl3:urea. To avoid a molecular weight influence on the ionogel rheological properties, polymers with molecular weight close to 100,000 g mol−1 have been chosen. The polymers considered include poly(ε-caprolactone) (PCL), poly(dimethyl siloxane) (PDMS), poly(vinyl pyrrolidone) (PVP), polyformal, thermoplastic polyurethanes, polymethacrylates, polyacetates and the elastomer SEBS. It was found that together with polyethylene oxide, only poly(ε-caprolactone) and poly(dimethyl siloxane) are soluble and produce gel electrolytes with AlCl3:urea. The solubility rules of polymers in chloroaluminates are discussed. The stripping/plating of Al and the ionic conductivity of PEO, PDMS and PCL ionogels are studied by cyclic voltammetry and impedance spectroscopy. PDMS proves to be as efficient as PEO to produce ionogels at low polymer concentration, that are also self-standing and electroactive, whereas a higher concentration of PCL is required to produce self-standing gels. The molecular structure of the ionogels and the modification of the chloroaluminate speciation is studied by vibrational spectroscopies, and supported by DFT calculations.

Room Temperature to 150 °C Lithium Metal Batteries Enabled by a Rigid Molecular Ionic Composite Electrolyte

AbstractMolecular ionic composites (MICs), made from ionic liquids and a rigid‐rod polymer poly(2,2′‐disulfonyl‐4,4′‐benzidine terephthalamide) (PBDT), are a new type of rigid gel electrolyte that combine fast ion transport with high thermal stability and mechanical strength. In this work, a MIC electrolyte membrane is prepared that is composed of PBDT, lithium bis(trifluoromethylsulfonyl)imide (LiTFSI), and 1‐butyl‐1‐methylpyrrolidinium bis(trifluoromethylsulfonyl)imide (Pyr14TFSI) in a mass ratio of 10:10:80. The ionic conductivity at 25 °C is 0.56 mS cm−1 with no added flammable/volatile components. Although the polymer content is only 10 wt%, this MIC membrane is rigid with a tensile modulus of 410 MPa at room temperature. The MIC membrane remains stable and rigid at 200 °C with the shear storage modulus (G′) only slightly decreasing by 35%. Li/MIC/LiFePO4 cells demonstrate stable cycling performance over a wide temperature range from 23 to 150 °C. The specific discharge capacity at 100 and 150 °C at 1 C rate exceeds 160 mAh g−1. The discharge capacity retention is 99% after 50 cycles at 150 °C. This stable battery performance shows that this low polymer content MIC membrane qualifies for use as a solid electrolyte in lithium metal batteries operating over a wide temperature range.

Facile way of dynamically tailoring microporous structures in polyvinylidene fluoride films prepared by thermally induced phase separation

AbstractPolyvinylidene fluoride (PVDF) films were prepared via thermally induced phase separation (TIPS) using diphenyl carbonate as the diluter in an attempt to disclose the competitive relationship between crystal growth and droplet growth during phase separation process. By varying the quenching temperature different temperature gradient fields were established, which were theoretically evaluated via enthalpy transformation method. The effects of polymer concentration and quenching temperature on evolution of hierarchical morphologies in TIPS films were systematically investigated. According to the morphological characteristics, the cross‐sectional morphology of the films with lower polymer concentration (ΦP = 25%) could be divided into three layers; while that of higher polymer concentration counterpart (ΦP = 55%) only presented a bi‐layered structure. The reason for this could be ascribed to the effect of cooling rate on both crystal growth and droplet growth during TIPS process, which further determined the formation of the hierarchical structure in microporous films. With an increasing quenching temperature, both pore size and porosity of PVDF films increased, accompanied by an improvement on both thermal stability and dynamic mechanical thermal property. The present study could insightfully supply a facile route to fabricate structure‐controllable microporous films of crystalline polymers via an appropriate regulation of the TIPS quenching parameters.

The Influence of the Strength of Drug-Polymer Interactions on the Dissolution of Amorphous Solid Dispersions.

In an earlier report, ionic interactions between ketoconazole (KTZ), a weakly basic drug, and poly(acrylic acid) (PAA), an anionic polymer, resulted in a dramatic decrease in molecular mobility as well as reduced crystallization propensity of amorphous solid dispersion (ASD) in the solid state. On the other hand, weaker dipole-dipole interactions between KTZ and polyvinylpyrrolidone (PVP) resulted in ASDs with higher crystallization propensity (Mistry Mol Pharm., 2015, 12 (9), 3339-3350). In this work, we investigated the behavior of the ketoconazole (KTZ) solid dispersions in aqueous media. In vitro dissolution tests showed that the PAA ASD maintained the level of supersaturation for a longer duration than the PVP ASD at low polymer contents (4-20% w/w polymer). Additionally, the PAA ASDs were more resistant to drug crystallization in aqueous medium when measured with synchrotron X-ray diffractometry. Two-dimensional 1H nuclear Overhauser effect spectroscopy (NOESY) NMR cross peaks between ketoconazole and PAA confirmed the existence of drug-polymer interactions in D2O. The interaction was accompanied by a reduced drug diffusivity as monitored by 2D diffusion ordered spectroscopy (DOSY) NMR and enthalpy-driven when characterized by isothermal titration calorimetry (ITC). On the other hand, drug-polymer interactions were not detected between ketoconazole and PVP in aqueous solution, with NOESY, DOSY, or ITC. The results suggest that interactions that stabilize ASDs in the solid state can also be relevant and important in sustaining supersaturation in solution.

Creation of highly stable porous polyacrylonitrile membranes using infrared heating

Highly stable porous membranes made of commercial polyacrylonitrile (PAN) were developed for high pressure application in aprotic solvents. The membranes prepared by NIPS method from the casting solution with PAN concentration of 15 or 18 wt% in DMSO demonstrated good mechanical stability towards the transmembrane pressure of 30 bar and MWCO of 22 and 14.5 kg/mol, respectively; whereas the lower polymer concentration (12 wt%) led to collapsing of porous structure based on SEM data. By adjustment of treatment time and temperature, it was shown that the porous PAN membranes became insoluble in aprotic solvents such as DMSO, DMF, DMAc, and NMP after 5 min of infrared heating at 170 °C. The analysis of the data obtained by SEM, liquid-liquid displacement porosimetry, solvent filtration, and MWCO revealed that such IR treatment did not noticeably change the membrane structure and properties originally formed during the membrane casting. Replacement of conventional heating reported in the literature by IR heating allowed to reduce the treatment time from 6 h at 250 °C down to 5 min at 170 °C (estimated energy saving by a factor of 6.5). The mechanism of the transformation of PAN into insoluble form was proposed based on the data of FTIR analysis. The hypothesized role of adsorbed water molecules in accelerating cross-linking of PAN upon the near-IR heating was considered and discussed. IR treated PAN membranes can be employed as porous supports for solvent resistant nanofiltration membranes or directly as ultrafiltration membranes for non-aqueous applications.

Experimental Investigation of Polymer Enhanced Oil Recovery under Different Injection Modes.

To solve the problem of poor adaptability of the single slug polymer injection mode which lead to profile inversion, non-effective circulation of polymer solution in the high permeability zone during the development of conventional heavy oil, new technology of alternative injection, and three-stage slug injection for further improving polymer flooding performance were developed. Parallel sandpack flooding experiment was conducted to study the oil displacement efficiency of different injection modes, and reasonable injection mode and optimal slug combination of polymer flooding are selected. The results show that under the same polymer dosage, the high and low mass concentration polymer slug alternative injection is better than the three-stage slug and single slug polymer flooding, and with the increase of the alternating rounds, the polymer flooding performance increased first and then decreased. Compared with the single slug injection, the alternative injection increased the recovery factor by 4%. When the three-stage slug is injected, the concentration of the front and post slug has a significant effect on the oil displacement process. The optimal oil displacement formulations are as follows: main slug 5000 mg/L × 0.125 PV, secondary slug 3000 mg/L × 0.208 PV, alternating two rounds.

Direct Simulations of Phase Behavior of Mixtures of Oppositely Charged Proteins/Nanoparticles and Polyelectrolytes.

We use direct simulations of particle-polyelectrolyte mixtures using the single chain in mean field framework to extract the phase diagram for such systems. At high charges of the particles and low concentration of polymers, we observe the formation of a coacervate phase involving the particles and polyelectrolytes. At low particle charges and/or high concentration of polymers, the mixture undergoes a segregative phase separation into particle-rich and polymer-rich phases, respectively. We also present results for the influence of particle charge heterogeneity on the phase diagram.

Optimization of the fabrication of amidoxime modified PIM-1 electrospun fibres for use as breathable and reactive materials

This study reports the preparation of waterproof/breathable films based on amidoxime functionalized PIM-1, which were processed into fibrous membrane using the electrospinning process with a green solvent, i.e. dimethyl sulfoxide. The influence of the feed solution (polymer concentration, solvent nature, presence of salt) and the electrospinning process conditions (flow rate, distance between the tip and the collector and voltage) has been investigated in order to obtain bead-free, thin fibres with regular structure and low porosity. The addition of salt allowed the production of nanofibres at low polymer concentration, resulting in the fabrication of fibrous mats with 1.5 μm diameter fibres and porosity below 10 μm. These fibre mats possess a hydrophobic character with a contact angle superior to 90°. Moreover, they are breathable, but not permeable to liquid water, which is essential for use within protective gear (i.e. gas masks or protective clothing).

Tuning Size and Morphology of mPEG-b-p(HPMA-Bz) Copolymer Self-Assemblies Using Microfluidics.

The careful design of nanoparticles, in terms of size and morphology, is of great importance to developing effective drug delivery systems. The ability to precisely tailor nanoparticles in size and morphology during polymer self-assembly was therefore investigated. Four poly(ethylene glycol)-b-poly(N-2-benzoyloxypropyl methacrylamide) mPEG-b-p(HPMA-Bz) block copolymers with a fixed hydrophilic block of mPEG 5 kDa and a varying molecular weight of the hydrophobic p(HPMA-Bz) block (A: 17.1, B: 10.0, C: 5.2 and D: 2.7 kDa) were self-assembled into nanoparticles by nanoprecipitation under well-defined flow conditions, using microfluidics, at different concentrations. The nanoparticles from polymer A, increased in size from 55 to 90 nm using lower polymer concentrations and slower flow rates and even polymer vesicles were formed along with micelles. Similarly, nanoparticles from polymer D increased in size from 35 to 70 nm at slower flow rates and also formed vesicles along with micelles, regardless of the used concentration. Differently, polymers B and C mainly self-assembled into micelles at the different applied flow rates with negligible size difference. In conclusion, this study demonstrates that the self-assembly of mPEG-b-p(HPMA-Bz) block copolymers can be easily tailored in size and morphology using microfluidics and is therefore an attractive option for further scaled-up production activities.

Novel Electrospun Pullulan Fibers Incorporating Hydroxypropyl-β-Cyclodextrin: Morphology and Relation with Rheological Properties.

Fibers produced by electrospinning from biocompatible, biodegradable and naturally occurring polymers have potential advantages in drug delivery and biomedical applications because of their unique functionalities. Here, electrospun submicron fibers were produced from mixtures containing an exopolysaccharide (pullulan) and a small molecule with hosting abilities, hydroxypropyl-β-cyclodextrin (HP-β-CD), thus serving as multi-functional blend. The procedure used water as sole solvent and excluded synthetic polymers. Rheological characterization was performed to evaluate the impact of HP-β-CD on pullulan entanglement concentration (CE); the relationship with electrospinnability and fiber morphology was investigated. Neat pullulan solutions required three times CE (~20% w/v pullulan) for effective electrospinning and formation of bead-free nanofibers. HP-β-CD (30% w/v) facilitated electrospinning, leading to the production of continuous, beadless fibers (average diameters: 853-1019 nm) at lower polymer concentrations than those required in neat pullulan systems, without significantly shifting the polymer CE. Rheological, Differential Scanning Calorimetry (DSC) and Dynamic Light Scattering (DLS) measurements suggested that electrospinnability improvement was due to HP-β-CD assisting in pullulan entanglement, probably acting as a crosslinker. Yet, the type of association was not clearly identified. This study shows that blending pullulan with HP-β-CD offers a platform to exploit the inherent properties and advantages of both components in encapsulation applications.