Multicompartment Particles Research Articles

Fabrication and Performance of Bubble-Containing Multicompartmental Particles: Novel Self-Orienting Carriers.

In this work, a class of bubble-containing multicompartmental particles with self-orienting capability is developed, where a single bubble is enclosed at the top of the super-segmented architecture. Such bubbles, driven by potential energy minimization, cause the particles to have a bubble-upward preferred orientation in liquid, enabling efficient decoding of their high-density signals in an interference-resistant manner. The particle preparation involves bubble encapsulation via the impact of a multicompartmental droplet on the liquid surface and overall stabilization via rational crosslinking. The conditions for obtaining these particles are systematically investigated. Methodological compatibility with materials is demonstrated by different hydrogel particles. Finally, by encapsulating cargoes of interest, these particles have found broad applications in actuators, multiplexed detection, barcodes, and multicellular systems.

Multicompartment Micro- and Nanoparticles Using Supramolecular Assembly of Core-Shell Bottlebrush Polymers.

Multicompartment particles have been produced to date by the self-assembly of linear multiblock polymers. Besides the large diversity of structures that can be obtained with this approach, these are highly sensitive to dilution and environmental factors. Here we show that using core-shell bottlebrush polymers with a hydrophobic polyester core as starting materials it is possible to create compartmentalized particles from the micrometer size down to the molecular scale. These polymers can be used as building blocks to create multicompartment particles and networks via a self-assembly process. The polymers can encapsulate active compounds and slowly degrade in water into polymeric micelles, making them promising materials for drug delivery applications.

Recent Progress of Droplet Microfluidic Emulsification Based Synthesis of Functional Microparticles.

The remarkable control function over the functional material formation process enabled by droplet microfluidic emulsification approaches can lead to the efficient and one-step encapsulation of active substances in microparticles, with the microparticle characteristics well regulated. In comparison to the conventional fabrication methods, droplet microfluidic technology can not only construct microparticles with various shapes, but also provide excellent templates, which enrich and expand the application fields of microparticles. For instance, intersection with disciplines in pharmacy, life sciences, and others, modifying the structure of microspheres and appending functional materials can be completed in the preparation of microparticles. The as-prepared polymer particles have great potential in a wide range of applications for chemical analysis, heavy metal adsorption, and detection. This review systematically introduces the devices and basic principles of particle preparation using droplet microfluidic technology and discusses the research of functional microparticle formation with high monodispersity, involving a plethora of types including spherical, nonspherical, and Janus type, as well as core-shell, hole-shell, and controllable multicompartment particles. Moreover, this review paper also exhibits a critical analysis of the current status and existing challenges, and outlook of the future development in the emerging fields has been discussed.

Dual-Drug Delivery by Anisotropic and Uniform Hybrid Nanostructures: A Comparative Study of the Function and Substrate-Drug Interaction Properties.

By utilizing nanoparticles to upload and interact with several pharmaceuticals in varying methods, the primary obstacles associated with loading two or more medications or cargos with different characteristics may be addressed. Therefore, it is feasible to evaluate the benefits provided by co-delivery systems utilizing nanoparticles by investigating the properties and functions of the commonly used structures, such as multi- or simultaneous-stage controlled release, synergic effect, enhanced targetability, and internalization. However, due to the unique surface or core features of each hybrid design, the eventual drug-carrier interactions, release, and penetration processes may vary. Our review article focused on the drug's loading, binding interactions, release, physiochemical, and surface functionalization features, as well as the varying internalization and cytotoxicity of each structure that may aid in the selection of an appropriate design. This was achieved by comparing the actions of uniform-surfaced hybrid particles (such as core-shell particles) to those of anisotropic, asymmetrical hybrid particles (such as Janus, multicompartment, or patchy particles). Information is provided on the use of homogeneous or heterogeneous particles with specified characteristics for the simultaneous delivery of various cargos, possibly enhancing the efficacy of treatment techniques for illnesses such as cancer.

Engineered multicompartment vesicosomes for selective uptake by living cells

Small extracellular vesicles (sEVs) have attracted tremendous interest in recent years due to their exceptional properties for therapeutic and diagnostic applications. Although much research was focused on the quantity and content of sEVs, less efforts have been put into discovering the interaction between sEVs and cells. Here we engineered multicompartment particles, termed vesicosomes, by deposition of sEVs derived from MCF7, CHO cells and human plasma onto the surface of polyelectrolyte (PE)-coated silica (SiO2) microparticles. Uptake of the PE-coated SiO2 microparticles by parent cells was significantly enhanced by coating them with sEVs, compared to PE-coated SiO2 microparticles independent of the terminated polyelectrolyte layer. This study highlights the emerging role of sEVs membrane receptors in the sEV-cells interaction and demonstrates the potential application of sEV-like multicompartment particles as therapeutic carriers.

Poly(vinylpyridine)-containing block copolymers for smart, multicompartment particles

This review summarizes recent progress in smart multicompartment particles based on PVP-containing block copolymers, including their preparation strategies, properties, and applications.

Microfluidic Preparation of Janus Microparticles With Temperature and pH Triggered Degradation Properties.

Based on the phase separation phenomenon in micro-droplets, polymer-lipid Janus particles were prepared on a microfluidic flow focusing chip. Phase separation of droplets was caused by solvent volatilization and Janus morphology was formed under the action of interfacial tension. Because phase change from solid to liquid of the lipid hemisphere could be triggered by physiological temperature, the lipid hemisphere could be used for rapid release of drugs. While the polymer we selected was pH sensitive that the polymer hemisphere could degrade under acidic conditions, making it possible to release drugs in a specific pH environment, such as tumor tissues. Janus particles with different structures were obtained by changing the experimental conditions. To widen the application range of the particles, fatty alcohol and fatty acid-based phase change materials were also employed to prepare the particles, such as 1-tetradecanol, 1-hexadecanol and lauric acid. The melting points of these substances are higher than the physiological temperature, which can be applied in fever triggered drug release or in thermotherapy. The introduction of poly (lactic-co-glycolic acid) enabled the formation of multicompartment particles with three distinct materials. With different degradation properties of each compartment, the particles generated in this work may find applications in programmed and sequential drug release triggered by multiple stimuli.

Natural polysaccharide based complex drug delivery system from microfluidic electrospray for wound healing

Natural polysaccharides have a demonstrated value in drug encapsulation and delivery. Efforts in this area are focused on improving the performances of these biomaterials. In this study, we present a multicompartment polysaccharide core-shell microparticle to construct a sustainable dual-release system of active molecules for enhancing wound healing. These microparticles were generated utilizing a microfluidic electrospray approach, in which a mixture of cellulose nanocrystals (CNC) and vascular endothelial growth factor (VEGF) were employed as the cores, with doxycycline hydrochloride (DH) mixed alginate as the shells. The resultant multicompartment particles exhibited wonderful antibacterial properties inherited from the alginate shell, and angiogenesis properties from the CNC core after the shell disintegrated. It was demonstrated that these core-shell microparticles performed their outstanding capabilities in inhibiting inflammation, promoting granulation tissue formation, collagen deposition, and angiogenesis, thereby accelerating rodents’ wound healing. These findings support the great potential value of CNC/alginate core-shell microparticles based on the synergistic drug delivery strategy for orchestrating wound healing.

Concepts for efficient preparation of particulate polymer carrier systems by droplet-based microfluidics.

Droplet-based microfluidics has grown out of its infancy as technical solutions became available for a broad community of researchers aiming at highly defined structures of polymer-based drug carrier systems. While the beauty of obtained particles and the precision of their (continuous) production may be very fascinating from a scientific perspective, microfluidics is further developing towards the use in production processes. This review summarizes recent concepts and developments in droplet-based microfluidics covering theoretical aspects of the operation principle as well as approaches to increased throughput and thus to enable efficient production. The application of microfluidic templating for preparing functional polymer particles including dispersions of preformed polymers, multicompartment particles and the use of template droplets as microreactors for carrier synthesis are also included. When operated at high-throughput, in a continuous process and with excellent control over particle properties, microfluidics may become a preparation technique for particulate carriers competitive to batch emulsification not only in research but also for commercial fabrication, e.g., of individualized, patient-specific formulations.

Bioinspired design of amphiphilic particles with tailored compartments for dual-drug controlled release.

Inspired by the phenomenon of water droplets hanging over rose petals, we propose a green interfacial self-assembly strategy to construct amphiphilic particles with controllable compartments for dual-drug encapsulation and controlled release. The method involves fabrication of "sticky" superhydrophobic materials, assembling superhydrophilic hydrogel beads with "sticky" superhydrophobic material into an amphiphilic particle, and amphiphilicity induced self-organization of several small amphiphilic particles into a large-sized amphiphilic multicompartmental particle. With the employment of this approach, amphiphilic particles with tailored sizes, controllable morphology, and tunable numbers of compartments are successfully constructed. The formation process and the underlying principle are further clarified. We finally investigate the potential application of the amphiphilic multicompartmental particles to load both hydrophilic and hydrophobic species in separated domains and release them in a controllable manner without interference. This novel approach may offer a new route to generate amphiphilic materials for the purpose of multidrug combination therapy, multiple-cell encapsulation, and so on.

Controllable Synthesis of Multicompartmental Particles Using 3D Microfluidics

AbstractA microfluidic assembly method based on a microfluidic chip and capillary device was developed to create multicompartmental particles. The microfluidic chip design endows the particles with regulable internal structure. By adjusting the microstructure of the chip, the diameter of the capillary, the gap length between the two microfluidic components, and the flow rates, the size of the particles and the number or the ratio of different regions within the particle could be widely varied. As a proof of concept, we have produced some complicated particles that even contain 20 compartments. Furthermore, the potential applications of the anisotropic particles are explored by encapsulating magnetic beads, fluorescent nanoparticles, and the cells into different compartments of the microparticles. We believe that this method will open new avenues for the design and application of multicompartmental particles.

Controllable Synthesis of Multicompartmental Particles Using 3D Microfluidics.

A microfluidic assembly method based on a microfluidic chip and capillary device was developed to create multicompartmental particles. The microfluidic chip design endows the particles with regulable internal structure. By adjusting the microstructure of the chip, the diameter of the capillary, the gap length between the two microfluidic components, and the flow rates, the size of the particles and the number or the ratio of different regions within the particle could be widely varied. As a proof of concept, we have produced some complicated particles that even contain 20 compartments. Furthermore, the potential applications of the anisotropic particles are explored by encapsulating magnetic beads, fluorescent nanoparticles, and the cells into different compartments of the microparticles. We believe that this method will open new avenues for the design and application of multicompartmental particles.

Progress of Multicompartmental Particles for Medical Applications.

Particulate materials are becoming increasingly used in the literature for medical applications, but translation to the clinical setting has remained challenging as many particle systems face challenges from in vivo barriers. Multicompartmental particles that can incorporate several materials in an individual particle may allow for more intricate control and addressing of issues that otherwise standard particles are unable to. Here, some of the advances made in the use of multicompartmental particles for medical applications are briefly described.

Synthesis of Oil-Laden Poly(ethylene glycol) Diacrylate Hydrogel Nanocapsules from Double Nanoemulsions.

Multiple emulsions have received great interest due to their ability to be used as templates for the production of multicompartment particles for a variety of applications. However, scaling these complex droplets to nanoscale dimensions has been a challenge due to limitations on their fabrication methods. Here, we report the development of oil-in-water-in-oil (O1/W/O2) double nanoemulsions via a two-step high-energy method and their use as templates for complex nanogels comprised of inner oil droplets encapsulated within a hydrogel matrix. Using a combination of characterization methods, we determine how the properties of the nanogels are controlled by the size, stability, internal morphology, and chemical composition of the nanoemulsion templates from which they are formed. This allows for identification of compositional and emulsification parameters that can be used to optimize the size and oil encapsulation efficiency of the nanogels. Our templating method produces oil-laden nanogels with high oil encapsulation efficiencies and average diameters of 200-300 nm. In addition, we demonstrate the versatility of the system by varying the types of inner oil, the hydrogel chemistry, the amount of inner oil, and the hydrogel network cross-link density. These nontoxic oil-laden nanogels have potential applications in food, pharmaceutical, and cosmetic formulations.

Nanostructured raspberry-like gelatin microspheres for local delivery of multiple biomolecules.

Multicompartment particles have gained considerable interest during the past decade to facilitate simultaneous and differential delivery of multiple biomolecules in various biomedical applications. Nevertheless, common methods employed for the production of such particles are often complex and only offer small-scale production. Here, we report the formation of raspberry-like gelatin (RLG) microparticles composed of gelatin nanoparticles as colloidal building blocks through supercritical CO2 processing. We show that these microparticles are cytocompatible and facilitate differential release of two model compounds with different molecular sizes, promising successful applications in various biomedical areas. Summarizing, this paper presents a novel strategy that can be utilized as a cost-effective route for production of various types of multicompartment particles using a wide range of colloidal building blocks.

Fabrication of Multicompartment Particles via Sequential Micromolding Method

본 연구는 순차적인 마이크로 몰딩 방법을 이용한 고분자 다중 분획 입자 제조 방법에 관한 것이다. 다중 분획 입자는 poly(dimethylsiloxane)(PDMS) 마이크로 몰드 내로 단량체 혼합물의 주입, 휘발성 용매의 증발, 광중합으로 이루어지는 일련의 과정을 통해 제조한다. 이때, 단량체 혼합물에 포함된 휘발성 용매의 농도에 따라, 다중 분획입자를 구성하는 각 구획의 부피분율을 제어하는 것이 가능하다. 또한 단량체 혼합물의 농도 및 다중 분획 입자 제조공정의 반복횟수에 따라, 단일 입자, 이중 입자, 삼중 입자를 선택적으로 제조가 가능함을 보여준다. 제조한 각각의 다중 분획 입자에 형광염료를 함입하여 특정한 정보를 인코딩한 바코드 입자로써의 활용 가능성을 증명한다. 본 연구에서 제안하는 다중 분획 입자를 제조하기 위한 순차적인 마이크로 몰딩 방법은 쉽고, 빠르며, 고가의 장비를 필요로 하지 않는 장점을 가지며, 제조된 다중 분획 입자는 약물 저장 및 전달 소재, 바이오 센서, 그리고 선택적인 흡착-탈착을 유도할 수 있는 고감도 기능성 재료로서 응용이 가능할 것으로 기대한다.

Microfluidic Synthesis of pH-Sensitive Multicompartmental Microparticles for Multimodulated Drug Release.

Stimuli-responsive carriers releasing multiple drugs have been researched for synergistic combinatorial cancer treatment with reduced side-effects. However, previously used drug carriers have limitations in encapsulating multiple drug components in a single carrier and releasing each drug independently. In this work, pH-sensitive, multimodulated, anisotropic drug carrier particles are synthesized using an acid-cleavable polymer and stop-flow lithography. The particles exhibit a faster drug release rate at the acidic pH of tumors than at physiological pH, demonstrating their potential for tumor-selective drug release. The drug release rate of the particles can be adjusted by controlling the monomer composition. To accomplish multimodulated drug release, multicompartmental particles are synthesized. The drug release profile of each compartment is programmed by tailoring the monomer composition. These pH-sensitive, multicompartmental particles are promising drug carriers enabling tumor-selective and multimodulated release of multiple drugs for synergistic combination cancer therapy.

Formation of multi-compartmental particles by controlled aggregation of liposomes

The formation of multi-compartmental colloidal particles by controlled aggregation of 100nm cationic liposomes was investigated. The aggregation was performed under quiescent (perikinetic) conditions and was controlled by the ionic strength of the solution. The time required for obtaining 500nm particles by liposome aggregation ranged from several hours to a few minutes when increasing the NaCl concentration from 50mM to 100mM. It was shown that the aggregation process can be effectively terminated by capping the liposome clusters by a biocompatible non-ionic polymeric surfactant (Poloxamer 188). The clusters were stable in time and resistant to further increase in ionic strength as well as to mechanical agitation. These results demonstrate that multi-compartmental liposome-based carriers with a controlled size can be prepared in a relatively simple and robust way, and used for further studies in environments with variable salinity and hydrodynamic conditions.

Controlled fabrication of multicompartmental polymeric microparticles by sequential micromolding via surface-tension-induced droplet formation.

Polymeric multicompartmental microparticles have significant potential in many applications due to the capability to hold various functions in discrete domains within a single particle. Despite recent progress in microfluidic techniques, simple and scalable fabrication methods for multicompartmental particles remain challenging. This study reports a simple sequential micromolding method to produce monodisperse multicompartmental particles with precisely controllable size, shape, and compartmentalization. Specifically, our fabrication procedure involves sequential formation of primary and secondary compartments in micromolds via surface-tension-induced droplet formation coupled with simple photopolymerization. Results show that monodisperse bicompartmental particles with precisely controllable size, shape, and chemistry can be readily fabricated without sophisticated control or equipment. This technique is then extended to produce multicompartmental particles with controllable number of compartments and their size ratios through simple design of mold geometry. Also, core-shell particles with controlled number of cores for primary compartments can be readily produced by simple tuning of wettability. Finally, we demonstrate that the as-prepared multicompartmental particles can exhibit controlled release of multiple payloads based on design of particle compositions. Combined, these results illustrate a simple, robust, and scalable fabrication of highly monodisperse and complex multicompartmental particles in a controlled manner based on sequential micromolding.

Three-dimensional printing-based electro-millifluidic devices for fabricating multi-compartment particles.

In this work, we demonstrate the use of stereolithographic 3D printing to fabricate millifluidic devices, which are used to engineer particles with multiple compartments. As the 3D design is directly transferred to the actual prototype, this method accommodates 3D millimeter-scaled features that are difficult to achieve by either lithographic-based microfabrication or traditional macrofabrication techniques. We exploit this approach to produce millifluidic networks to deliver multiple fluidic components. By taking advantage of the laminar flow, the fluidic components can form liquid jets with distinct patterns, and each pattern has clear boundaries between the liquid phases. Afterwards, droplets with controlled size are fabricated by spraying the liquid jet in an electric field, and subsequently converted to particles after a solidification step. As a demonstration, we fabricate calcium alginate particles with structures of (1) slice-by-slice multiple lamellae, (2) concentric core-shells, and (3) petals surrounding the particle centers. Furthermore, distinct hybrid particles combining two or more of the above structures are also obtained. These compartmentalized particles impart spatially dependent functionalities and properties. To show their applicability, various ingredients, including fruit juices, drugs, and magnetic nanoparticles are encapsulated in the different compartments as proof-of-concepts for applications, including food, drug delivery, and bioassays. Our 3D printed electro-millifluidic approach represents a convenient and robust method to extend the range of structures of functional particles.