Multicompartmental Materials by Electrohydrodynamic Cojetting

Event Abstract Back to Event One-step fabrication of polymeric hybrid particles with various anisotropic architectures via a microfluidic-assisted phase separation process and their application in controllable drug delivery Hua Dong1, 2, Wenxiu Li1 and Xiaodong Cao1, 2 1 School of Materials Science and Engineering, South China University of Technology, Department of Biomedical Engineering, China 2 South China University of Technology, National Engineering Research Center for Tissue Restoration and Reconstruction, China We report herein a one-step route to fabricate core-shell, patchy, patchy Janus and Janus particles via microfluidic-assisted phase separation process. As a proof of concept, PLGA/PCL hybrid particles are prepared and the results show that the four types of particles can be harvested with high yield and narrow size distribution by precise control over the phase separation process, or namely, interfacial tensions and spreading coefficients between immiscible phases, after generation of the single emulsion in microchannels[1]. The applications of Janus and core-shell particles in drug delivery are characterized via in vitro degradation behaviors, implying their capability of programmable drug delivery in different manners[2]. This research work was financially sponsored by the National Natural Science Foundation of China (Grant NO. 51373056, 51372085), Guangdong-Hongkong common technology bidding project (No.2013B010136003) and Fundamental Research Funds for the Central Universities.

Preparation of SiO2@EVA core–shell particles via post-emulsification method with polydisperse SiO2 particle sizes and the critical thickness-to-diameter ratio in PA6/SiO2@EVA system

The effect of strain on core–shell MOFcore@MOFshell particles is discussed and compared with that observed for analogous Janus particles. Whereas Janus particles do not display any effect of strain, the core of fully coated core–shell particles collapsed upon the formation of the outer shell, leaving the core inaccessible for guest adsorption. This suggests that Janus particles might become ideal candidates for gas separation, while core–shell particles could play a key role in sequestration of guest molecules.

Background: Nanoparticles with controlled physical properties have been widely used for controlled release applications. In addition to shape, the anisotropic nature of the particles can be an important design criterion to ensure selective surface modification or independent release of combinations of drugs.Purpose: Electrohydrodynamic (EHD) co-jetting is used for the fabrication of uniform anisotropic nanoparticles with individual compartments and initial physicochemical and biological characterization is reported.Methods: EHD co-jetting is used to create nanoparticles, which are characterized at each stage with scanning electron microscopy (SEM), structured illumination microscopy (SIM), dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA). Surface immobilization techniques are used to incorporate polyethylene glycol (PEG) and I125 radiolabels into the nanoparticles. Particles are injected in mice and the particle distribution after 1, 4 and 24 hours is assessed.Results and discussion: Nanoparticles with an average diameter of 105.7 nm are prepared by EHD co-jetting. The particles contain functional chemical groups for further surface modification and radiolabeling. The density of PEG molecules attached to the surface of nanoparticles is determined to range between 0.02 and 6.04 ligands per square nanometer. A significant fraction of the nanoparticles (1.2% injected dose per mass of organ) circulates in the blood after 24 h.Conclusion: EHD co-jetting is a versatile method for the fabrication of nanoparticles for drug delivery. Circulation of the nanoparticles for 24 h is a pre-requisite for subsequent studies to explore defined targeting of the nanoparticles to a specific anatomic site.

Pt deposited Pt–Pd/C electrocatalysts with the enhanced oxygen reduction activity

Structure–property relationship in typical polypropylene/polycarbonate/poly[styrene-b-(ethylene-co-butylene)-b-styrene] (PP/PC/SEBS) ternary blends containing maleated SEBS (SEBS-g-MAH) was investigated. Three grades of PC with different melt viscosities were used, and changes in blend morphology from PC/SEBS core–shell particles partially surrounded by SEBS-g-MAH to inverse SEBS/PC core–shell particles in PP matrix were observed upon varying the viscosity ratio of PC to SEBS. It was found that the viscosity ratio completely controls the size of the core–shell droplets and governs the type, population, and shape of the dispersed domains, as evidenced by rheological, mechanical, and thermomechanical behavioral assessments. Dynamic mechanical analysis of samples with common (PC–SEBS) and inverse (SEBS–PC) core–shell particles revealed that they show completely different behaviors: blends containing PC–SEBS presented a higher storage and loss modulus, while blends containing SEBS–PC exhibited a lower β-transition temperature. Moreover, ternary blends with PC cores showed the highest Young’s modulus values and the lowest impact strength, due to the different fracture modes of the blends containing PC–SEBS and SEPS–PC core–shell droplets, which present debonding and shell-fracture mechanisms, respectively. Morphological observations of blends with high-molecular-weight PC demonstrated the presence of detached droplets and rods of PC in the PP matrix, along with composite core–shell and rod-like particles. Micrographs of the fracture surfaces confirmed the proposed mechanisms, given the presence of stretched (debonded) PC (SEBS) cores encapsulated by SEBS (PC), which require more (less) energy to achieve fracture. The correlation between the mechanical and morphological properties proves that decreasing core diameter and shell thickness has positive effects on the impact strength but decreases the Young’s modulus.

In this work, we describe a straightforward approach to produce monodisperse Janus and core-shell particles by using organic solvent free single emulsion droplet-based microfluidic device combining with off-chip polymerization. To accomplish this, methyl methacrylate (MMA) was used as both the oil phase and solvent to dissolve a polymerizable PEGbased macromolecular surfactant, instead of traditional surfactant, and the photo-initiator. Janus particles can be easily obtained by off-chip UV polymerization due to polymerization induced phase separation between PEG and the formed poly(methyl methacrylate). At the same time, core-shell particles can also be easily attained by inverting the original collecting tube several times and then exposing to UV light. These results may extend the scope of microfluidic technology and the studies on polymerization induced self-assembly/phase-separation into easy fabrication of various new functional materials.

Nanosized Janus and dendrimer particles have emerged as promising nanocarriers for the target-specific delivery and improved bioavailability of pharmaceuticals. Janus particles, with two distinct regions exhibiting different physical and chemical properties, provide a unique platform for the simultaneous delivery of multiple drugs or tissue-specific targeting. Conversely, dendrimers are branched, nanoscale polymers with well-defined surface functionalities that can be designed for improved drug targeting and release. Both Janus particles and dendrimers have demonstrated their potential to improve the solubility and stability of poorly water-soluble drugs, increase the intracellular uptake of drugs, and reduce their toxicity by controlling the release rate. The surface functionalities of these nanocarriers can be tailored to specific targets, such as overexpressed receptors on cancer cells, leading to enhanced drug efficacy The design of these nanocarriers can be optimized by tuning the size, shape, and surface functionalities, among other parameters. The incorporation of Janus and dendrimer particles into composite materials to create hybrid systems for enhancing drug delivery, leveraging the unique properties and functionalities of both materials, can offer promising outcomes. Nanosized Janus and dendrimer particles hold great promise for the delivery and improved bioavailability of pharmaceuticals. Further research is required to optimize these nanocarriers and bring them to the clinical setting to treat various diseases. This article discusses various nanosized Janus and dendrimer particles for target-specific delivery and bioavailability of pharmaceuticals. In addition, the development of Janus-dendrimer hybrid nanoparticles to address some limitations of standalone nanosized Janus and dendrimer particles is discussed.

In contrast to conventional particles that have isotropic surfaces, Janus (“two-faced”) particles have anisotropic surfaces, which leads to novel physicochemical properties and functional attributes. Janus particles with differing compositions, structures, and functional attributes have been prepared using a variety of fabrication methods. Depending on their composition, Janus particles have been classified as inorganic, polymeric, or polymeric/inorganic types. Recently, there has been growing interest in preparing Janus particles from biological macromolecules to meet the demand for a more sustainable and environmentally friendly food and pharmaceutical supply. At interfaces, Janus particles exhibit the characteristics of both surfactants and Pickering stabilizers, and so their behavior can be described using adsorption theories developed to describe these surface-active substances. Research has highlighted several potential applications of Janus particles in food and medicine, including emulsion formation and stabilization, toxin detection, antimicrobial activity, drug delivery, and medical imaging. Nevertheless, further research is needed to design and fabricate Janus particles that are suitable as functional ingredients in the food and biomedicine industries.

High performance liquid chromatography (HPLC) and ultrahigh performance liquid chromatography (UHPLC or UPLC) have been the most widely used tools for research and routine quality control of active pharmaceutical ingredients (API). The most important challenge in these techniques is fast and efficient separation. Both techniques are preferred due to their selectivity, high accuracy and remarkable precision. On the other hand, they have some limitations: In some cases, traditional HPLC uses high amounts of organic solvents with longer analysis time, and furthermore UHPLC has high back pressure and frictional heating. To overcome these limitations, scientists have developed new type of column particles. In general, two different silica types of column packing material based on their backbone have been used for HPLC and UHPLC. Stationary phases that have fully porous silica particles comply with the essential criteria of analysis, but these show all the limitations of HPLC. However, in recent years, core–shell silica particles (a combination of solid core and porous shell) have been increasingly used for highly efficient separation with reduced run times. Thus, core–shell technology provides the same efficient separations as the sub 2 µm particles that are used in UHPLC, while eliminating the disadvantages (potentially lower backpressure). The key factors for core–shell particles are size and thickness of porous shell layer, the latter of which can be explained using the Van Deemter equation. The columns packed with core–shell particles have been employed in a wide range of applications for analysis and quality control of pharmaceutical active substances. This review will underline the advantages of core–shell silica particles in the analysis of pharmaceutically active ingredients based on liquid chromatography from the perspective of column properties, system suitability test parameter results and validation steps.

In this study, we investigate a polyampholyte degradable core-shell (CS) microgel, with an anionic pH-sensitive core and a cationic pH- and temperature-sensitive shell, as a model system for drug delivery. The core was based on crosslinked poly(acrylic acid) and was synthesized through distillation precipitation polymerization. Then, the shell, based on cross-linked poly(poly(ethylene glycol) methyl ether methacrylate - N-(3-aminopropyl)methacrylamide), were built over the core via the seed polymerization. N,N′-bis(acryloyl)cystamine was used as the linker for cross-linking both core and shell to give the core-shell particles the ability to degrade in the presence of reducing agent. The swelling characteristics of the core-shell microgels were studied using dynamic light scattering (DLS). The core-shell particles exhibited sensitivity to pH due to the presence of carboxylic and amine groups in the core and shell, respectively. The degradation of the core-shell particles was examined using electron microscopy and DLS. In the presence of glutathione, which acts as a reducing agent for the -S-S- bridges, commonly found in cancer cells, the particles underwent complete degradation. Our findings also demonstrate that the presence of the positively charged shell still enables efficient uptake of a drug in the form of a cation (doxorubicin DOX) into the anionic core and the drug can be released through the cationic shell. The release of DOX from the carrier was studied under different pH conditions to mimic the environment found in cancer cells. The results showed that at pH 7.4, the carrier exhibited the lowest release of DOX. However, under conditions mimicking the acidic and reducing environment typically for tumor microenvironment (pH 5.0 and cGSH = 40 mM), the CS particles demonstrated the highest cumulative and sustained release of DOX. The results showed that the DOX-loaded particles exhibited increased cytotoxicity against MCF-7 cells, indicating enhanced anti-cancer activity. At the same time, these particles demonstrated reduced toxicity towards healthy MCF-10A cells, which suggests improved selectivity and reduced side effects. It is worth noting that the gel nanoparticles alone did not inhibit cell growth. Overall, these findings suggest that the DOX-loaded core-shell particles hold promise as a targeted drug delivery system, capable of preferentially releasing the drug in the acidic and reducing tumor microenvironment while minimizing toxicity towards healthy cells.

Core-shell (CS) particle consisting of Pt shell and base metal core is one of promising candidates of excellent electrode catalyst for fuel cell, because it is highly active and highly stable like Pt particle but less expensive than Pt particle. However, its stability has been unclear. Herein, icosahedral M13@Pt42 (M = 3d transition metals, Sc to Cu) CS particles consisting of Pt42 shell and M13 core are systematically investigated using DFT calculations. The CS structures of Co13@Pt42, Ni13@Pt42, and Cu13@Pt42 are calculated to be more stable than their non-core-shell (NCS) structures in which one 3d metal atom of the M13 core is exchanged with one Pt atom of the Pt42 shell. For Sc13Pt42, Ti13Pt42, V13Pt42, Cr13Pt42, Mn13Pt42, and Fe13Pt42, on the other hand, the NCS structure is more stable than the CS one. Small deformation energy of the Pt42 shell compared to that of the Pt41M shell and small stabilization energy by Pt-M exchange between the Pt42 shell and the M13 core are particularly important for stabilizing the CS structure. Late 3d metal elements in the first transition series of the periodic table such as Co, Ni, and Cu are suitable for producing a stable M13@Pt42 CS particle because their electronegativities are larger than those of the early and middle 3d transition metal elements and their atomic sizes are smaller than those of the early 3d metal elements such as Sc and Ti atoms. O2 adsorption to M13@Pt42 (M = Co, Ni, and Cu) CS particle occurs at the edge Pt atom and the vertex Pt atom in a side-on manner. The adsorption energies of O2 molecule to Co13@Pt42, Ni13@Pt42, and Cu13@Pt42 CS particles are smaller than that to Pt55 particle, indicating that the M13 core decreases the reactivity of the Pt42 shell for O2 adsorption.

Core–shell drug-carrier particles are known for their unique features. Due to the combination of superior properties not exhibited by the individual components, core–shell particles have gained a lot of interest. The structures could integrate core and shell characteristics and properties. These particles were designed for controlled drug release in the desired location. Therefore, the side effects would be minimized. So, these particles' advantages have led to the introduction of new methods and ideas for their fabrication. In the past few years, the generation of drug carrier core–shell particles in microfluidic chips has attracted much attention. This method makes it possible to produce particles at nanometer and micrometer levels of the same shape and size; it usually costs less than other methods. The other advantages of using microfluidic techniques compared to conventional bulk methods are integration capability, reproducibility, and higher efficiency. These advantages have created a positive outlook on this approach. This review gives an overview of the various fluidic concepts that are used to generate microparticles or nanoparticles. Also, an overview of traditional and more recent microfluidic devices and their design and structure for the generation of core–shell particles is given. The unique benefits of the microfluidic technique for core–shell drug carrier particle generation are demonstrated.

Advanced drug delivery systems for therapeutic applications.

Protein encapsulated core–shell structured particles prepared by coaxial electrospraying: Investigation on material and processing variables