Synthesis Of Polymeric Nanoparticles Research Articles

Block Copolymer Self-assembly: Exploitation of Hydrogen Bonding for Nanoparticle Morphology Control via Incorporation of Triazine Based Comonomers by RAFT Polymerization.

Synthesis of polymeric nanoparticles of controlled non-spherical morphology is of profound interest for a wide variety of potential applications. Self-assembly of amphiphilic diblock copolymers is an attractive bottom-up approach to prepare such nanoparticles. In the present work, RAFT polymerization is employed to synthesize a variety of poly(N,N-dimethylacrylamide)-b-poly[butyl acrylate-stat-GCB] copolymers, where GCB represents vinyl monomer containing triazine based Janus guanine-cytosine nucleobase motifs featuring multiple hydrogen bonding arrays. Hydrogen bonding between the hydrophobic blocks exert significant influence on the morphology of the resulting nanoparticles self-assembled in water. The Janus feature of the GCB moieties makes it possible to use a single polymer type in self-assembly, unlike previous work exploiting, e.g., thymine-containing polymer and adenine-containing polymer. Moreover, the strength of the hydrogen bonding interactions enables use of a low molar fraction of GCB units, thereby rendering it possible to use the present approach for copolymers based on common vinyl monomers for the development of advanced nanomaterials.

Polymeric Nanoparticles for Wound Healing.

Skin injury is one of the most prevalent lesions in humans, and many such wounds, including deep burns and chronic skin wounds, are notoriously difficult to heal. It has been established by medical practitioners that current wound therapies are not perfectly effective and are far from satisfactory. Meanwhile, nanotechnologies have made it possible to develop pharmaceutical formulations that can elevate the effectiveness of conventional pharmacotherapies to entirely new heights. Most nanostructured biomaterials used to treat wounds, including those that have helped establish this fascinating subject, have been polymeric. The bibliographic analysis presented here shows a steady growth in the research output of studies on the use of polymeric nanoparticles in wound healing therapies. This article provides an overview of polymeric nanoparticles for the treatment of wounds with an emphasis on different chemistries and polymer-drug combinations that have been proven the most effective. The wound age, pathophysiology, wound healing treatments of the present and past, as well as the physicochemical nature and methods for the synthesis of polymeric nanoparticles, are all covered in the opening parts of the review. The existing polymeric nano-drug delivery systems with the greatest promise for wound healing and skin regeneration are subsequently addressed and their potentials summarized.

Environmentally Friendly Synthesis of Polymer Nanoparticles in a Packed Reactor Using Glass Beads

AbstractPolymeric particles less than 100 nm in size (polymer nanoparticles), which are useful in the fields of medicine and so on, are synthesized through emulsion polymerization, wherein surfactants are essential for maintaining their dispersion stability, contaminating particle surfaces and causing high environmental pollution. The soap‐free emulsion polymerization (SFEP) of styrene in a packed reactor using microglass beads enables the synthesis of polymer nanoparticles without surfactants. Ultraviolet irradiation is used for radical polymerization using an initiator during the SFEP of styrene. The reaction space in the packed reactor is controlled by the size of glass beads to be filled in the reactor. A decrease in the size of the glass beads narrows the reaction space, causing the average polystyrene particle size to reach 27.3 nm and suppress convection flow by the wall of the glass beads, thereby limiting particle motion and preventing particle growth through particle collisions.This article is protected by copyright. All rights reserved

Photo-induced synthesis of polymeric nanoparticles and chemiluminescent degradable materials via flow chemistry.

We report the photo-induced, additive-free, continuous synthesis of polymeric particles using flow chemistry. Not only can these particles be formed under ambient conditions in a solely light-induced precipitation polymerisation, they can be prepared via continuous flow techniques to up-scale the synthetic process. We carefully assess the flow chemical parameters and analyse the resulting particles quantitatively using scanning electron microscopy (SEM). Particle formation is a direct result of the step-growth polymerisation via a photochemically induced AA + BB Diels-Alder reaction, which we herein base on the dialdehyde monomer (AA) derived from the sustainable precursor, thymol. By employing a peroxyoxalate bismaleimide (BB), we introduce particles that can be selectively degraded on-demand, self-reported by light emission through chemiluminescence.

Biogenic polymer nanoparticles to remove hydrophobic organic contaminants from water.

Soil and water pollution is of significant concern worldwide because of the consequences of environmental degradation and harmful effects on human health. Water bodies are very much polluted by various organic and inorganic pollutants by different human activities, including industrial wastes. Environmental pollution remains high because of urbanization-induced industrial developments and human lifestyle. It accumulates pollutants in the environment including plants and living organisms. Even mothers' milk is poisoned because of the uncontrolled, widespread increase in pollution. The discharge levels of organic hydrophobic contaminants in the water and soil are increasing rapidly. This severe pollution must be remediated to upgrade the environment and ensure the safety of human beings. It is vital to eradicate soil and water pollution to guarantee sufficient food and water. Different techniques available to remove the pollutants vary according to the type of pollutants. Hydrophobic contaminants are more dangerous than heavy metals and other pollutants; they cannot be easily removed, requiring special care. Hydrophobic organoxenobiotics released in the environment pose severe contamination in soil and water. Therefore, developing efficient and cost-effective processes is necessary to remove hydrophobic contaminants from soil and water. With nanoparticle-mediated remediation techniques, the green-synthesized nanoparticles exhibit improved performance. This review consolidates reports on the remediation techniques of hydrophobic contaminants, focusing on green-synthesized remediation agents. The very limited works on green synthesis of polymeric nanoparticles, particularly polyurethane-based materials for organic contaminants removal demand more attention in this area. PRACTITIONER POINTS: Consolidated the effects of hydrophobic organic and plastic contaminants on environment degradation. Summarized the advantages of green synthesized polymer nanoparticles for efficient removal of hydrophobic contaminants. Discussed the different sources of pollution and remediation techniques referring 112 research works.

Synthesis of polymer nanoparticles using methylcellulose gel as reactor

Synthesis of polymer nanoparticles using methylcellulose gel as reactor

Controlling size, shape, and charge of nanoparticles via low-energy miniemulsion and heterogeneous RAFT polymerization

Size, shape, and charge are key parameters of nanoparticles, and variations in these parameters can significantly impact their properties and applications. Among various nanoparticle synthesis methods, the combination of low-energy miniemulsions with reversible addition-fragmentation chain-transfer (RAFT) polymerization allows for the facile, rapid, and environmentally friendly preparation of uniform nanoparticles. However, this method cannot, yet, simultaneously control the size, shape, and charge of nanoparticles, thereby limiting its potential applications. Here we report the synthesis of polymeric nanoparticles with concurrent control over particle size, shape, and charge via low-energy miniemulsion and heterogeneous RAFT polymerization. Key to our approach is the combination of (i) a macromolecular surface-active agent to facilitate the formation of nanodroplets, (ii) various small-molecule surfactants with different charges to control the size and charge of nanodroplets, and (iii) a molecular transformer to control the morphology of the final polymeric nanoparticles. In particular, negatively charged polystyrene nanoparticles of different sizes (from ∼100 to ∼500 nm) and shapes (sphere, worm, and vesicle) were obtained by simply tuning the amount of added sodium dodecyl sulfate (SDS) and toluene. The nanoparticle charge was then switched from negative to positive by replacing SDS with cetyltrimethylammonium bromide (CTAB), a positively charged surfactant. In addition, biocompatible and neutral surfactants (including Tweens and Span 80) were employed to tune the nanoparticle size yielding challenging-to-synthesize nanoworms. This work provides a simple but powerful approach to produce nanoparticles of different properties, thus expanding the scope of nanomaterials made by RAFT low-energy miniemulsion polymerization.

Biomolecular engineering of drugs loading in Riboflavin-targeted polymeric devices: simulation and experimental

The synthesis of polymeric nanoparticles (NPs) with efficient drug loading content and targeting moieties is an attractive field and remains a challenge in drug delivery systems. Atomistic investigations can provide an in-depth understanding of delivery devices and reduce the number of expensive experiments. In this paper, we studied the self-assembly of poly (lactic-co-glycolic acid)-b-poly (ethylene glycol) with different molecular weights and surface compositions. The innovation of this molecular study is the loading of an antitumor drug (docetaxel) on a targeting ligand (riboflavin). According to this work, a novel, biocompatible and targeted system for cancer treatment has been developed. The obtained results revealed a correlation between polymer molecular weight and the stability of particles. In this line, samples including 20 and 10 w/w% moiety NPs formed from polymers with 3 and 4.5 kDa backbone sizes, respectively, are the stable models with the highest drug loading and entrapment efficiencies. Next, we evaluated NP morphology and found that NPs have a core/shell structure consisting of a hydrophobic core with a shell of poly (ethylene glycol) and riboflavin. Interestingly, morphology assessments confirmed that the targeting moiety located on the surface can improve drug delivery to receptors and cancerous cells. The developed models provided significant insight into the structure and morphology of NPs before the synthesis and further analysis of NPs in biological environments. However, in the best cases of this system, Dynamic Light Scattering (DLS) tests were also taken and the results were consistent with the results obtained from All Atom and Coarse Grained simulations.

Microfluidic Synthesis of Block Copolymer Micelles: Application as Drug Nanocarriers and as Photothermal Transductors When Loading Pd Nanosheets.

The synthesis of polymeric nanoparticles from a block copolymer based on poly(ethylene glycol) and a polymethacrylate containing the nucleobase analog 2,6-diacylaminopyridine is optimized by microfluidics to obtain homogeneous spherical micelles. Loading and delivery properties are studied using naproxen as a model. The incorporation of a Pd precursor in the polymer organic solution fed into the micromixer allows the preparation of Pd(II) precursor-polymer hybrid systems and the subsequent reduction with CO leads to the in situ synthesis of Pd nanosheets inside of the hydrophobic core of the polymeric micelles. This methodology is highly efficient to yield all polymeric nanoparticles loaded with Pd nanosheets as detected by electron microscopy and energy-dispersive X-ray spectroscopy. The cell viability of these Pd nanosheets-containing polymeric nanoparticles is evaluated using five cell lines, showing a high cytocompatibility at the tested concentrations without detrimental effects in cell membrane and nuclei. Furthermore, the use of these hybrid polymeric nanoparticles as photothermal transductors is evaluated using near infrared as irradiation source as well as its application in photothermal therapy using different cell lines demonstrating a high efficiency in all cell cultures.

Ouzo polymerization: A bottom-up green synthesis of polymer nanoparticles by free-radical polymerization of monomers spontaneously nucleated by the Ouzo effect; Application to molecular imprinting

HypothesisTop-down fabrication of polymer nanoparticles from preformed polymers by spontaneous colloid formation under influence of the Ouzo effect is a widely applied concept whereas bottom-up free-radical polymerization of monomers nucleated under the Ouzo regime have found limited application after a seminal report almost half a century ago. We hypothesized that the approach would be of value today as a versatile method for green synthesis of polymer nanoparticles, including molecularly imprinted ones. ExperimentsTernary mixtures of pentaerythritol triacrylate, ethanol, and water were prepared by either a one-pot-one-step batch-wise procedure or a continuous-flow process using a 3D-printed micro-fluidic mixer. The mixtures were subjected to free-radical polymerization. Cortisol was added as a template to generate a molecular memory through molecular imprinting. Characterization of the fabricated nanoparticles was carried out by dynamic light scattering, electron microscopy, and binding studies. FindingsCompositions in the Ouzo region of the ternary phase diagram provided spontaneous and instantaneous formation of nucleated monomer droplets. Free-radical polymerization, promoted by heat or UV light, transformed the droplets into polymer nanoparticles in a green and sustainable route. Addition of cortisol created polymer nanoparticles with high affinity for cortisol in aqueous media. Competition studies showed some cross-reaction with other steroids, comparable to that found with antibodies, and complete discrimination of structurally unrelated drug molecules.

Exploring Various Techniques for the Chemical and Biological Synthesis of Polymeric Nanoparticles

Nanoparticles (NPs) have remarkable properties for delivering therapeutic drugs to the body’s targeted cells. NPs have shown to be significantly more efficient as drug delivery carriers than micron-sized particles, which are quickly eliminated by the immune system. Biopolymer-based polymeric nanoparticles (PNPs) are colloidal systems composed of either natural or synthetic polymers and can be synthesized by the direct polymerization of monomers (e.g., emulsion polymerization, surfactant-free emulsion polymerization, mini-emulsion polymerization, micro-emulsion polymerization, and microbial polymerization) or by the dispersion of preformed polymers (e.g., nanoprecipitation, emulsification solvent evaporation, emulsification solvent diffusion, and salting-out). The desired characteristics of NPs and their target applications are determining factors in the choice of method used for their production. This review article aims to shed light on the different methods employed for the production of PNPs and to discuss the effect of experimental parameters on the physicochemical properties of PNPs. Thus, this review highlights specific properties of PNPs that can be tailored to be employed as drug carriers, especially in hospitals for point-of-care diagnostics for targeted therapies.

Synthesis of Polymer Nanoparticles in the Presence of Diatoms as Sustainable Bio-Templates

Synthesis of Polymer Nanoparticles in the Presence of Diatoms as Sustainable Bio-Templates

An aqueous photo-controlled polymerization under NIR wavelengths: synthesis of polymeric nanoparticles through thick barriers.

We report an aqueous and near-infrared (NIR) light mediated photoinduced reversible addition-fragmentation chain transfer (photo-RAFT) polymerization system using tetrasulfonated zinc phthalocyanine (ZnPcS4 -) as a photocatalyst. Owing to the high catalytic efficiency and excellent oxygen tolerance of this system, well-controlled polyacrylamides, polyacrylates, and polymethacrylates were synthesized at fast rates without requiring deoxygenation. Notably, NIR wavelengths possess enhanced light penetration through non-transparent barriers compared to UV and visible light, allowing high polymerization rates through barriers. Using 6.0 mm pig skin as a barrier, the polymerization rate was only reduced from 0.36 to 0.21 h-1, indicating potential for biomedical applications. Furthermore, longer wavelengths (higher λ) can be considered an ideal light source for dispersion photopolymerization, especially for the synthesis of large diameter (d) nanoparticles, as light scattering is proportional to d 6/λ 4. Therefore, this aqueous photo-RAFT system was applied to photoinduced polymerization-induced self-assembly (photo-PISA), enabling the synthesis of polymeric nanoparticles with various morphologies, including spheres, worms, and vesicles. Taking advantage of high penetration and reduced light scattering of NIR wavelengths, we demonstrate the first syntheses of polymeric nanoparticles with consistent morphologies through thick barriers.

High-speed continuous production of polymeric nanoparticles with improved stability using a self-aligned coaxial turbulent jet mixer

Continuous synthesis of polymeric nanoparticles (NPs) has been intensively studied due to its great potential to produce NPs with the physicochemical properties of reproducibility and controllability. Here, we developed a self-aligned coaxial turbulent jet mixer for high-speed continuous synthesis of polymeric NPs. The coaxial turbulent jet mixer can be constructed using commercial tube fittings and tubes. Since those fluidic components are self-aligned coaxially, leak-free jet mixers can be assembled without the use of tools or specialized skills in robust manner. Using the jet mixer with polystyrene (PS) solution, uniform polymeric NPs can be synthesized in a fully continuous manner, for which diaphragm pumps and pulsation dampers are used for continuous control of the flow. We also improved the dispersion stability of the PS NPs in aqueous solution against centrifugation by introducing polystyrene-poly(ethylene oxide) diblock copolymer (PS-b-PEO) as steric stabilizer. The NPs prepared using the coaxial turbulent jet mixer were smaller and more uniform in size compared to NPs synthesized by a bulk nanoprecipitation method.

Insight into drug encapsulation in polymeric nanoparticles using microfluidic nanoprecipitation

Synthesis of polymeric nanoparticles (NPs) through self-assembly of di-block copolymers have attracted substantial interest in the past decades for drug delivery and controlled release. Microfluidics offers a facile approach for making such NPs and drug encapsulation. However, a fundamental understanding of the drug encapsulation process is lacking. In this paper, we report a combined computational fluid dynamics (CFD) and experimental approach to illustrate the fundamental principle that governs the encapsulation of a drug in polymeric NPs through microfluidic nanoprecipitation. Taking a drug curcumin and a polymer poly (ethylene glycol)-block-poly (d, l-lactide-co-glycolide) (PEG-PLGA) as a model system, we demonstrated the different precipitation times of curcumin and PEG-PLGA as well as their mixing times in the microfluidic device. The big difference in their mixing times led to very low drug loading. This study provides a new perspective in understanding and controlling the formation of drug-loaded polymeric NPs and offers a new design rule for selecting the right combinations of drugs, polymers, solvents, and devices.

Synthesis of D-Limonene Loaded Polymeric Nanoparticles with Enhanced Antimicrobial Properties for Potential Application in Food Packaging.

Mini-emulsion polymerization was applied for the synthesis of cross-linked polymeric nanoparticles comprised of methyl methacrylate (MMA) and Triethylene Glycol Dimethacrylate (TEGDMA) copolymers, used as matrix-carriers for hosting D-limonene. D-limonene was selected as a model essential oil, well known for its pleasant odor and its enhanced antimicrobial properties. The synthesized particles were assessed for their morphology and geometric characteristics by Dynamic Light Scattering (DLS) and Scanning Electron Microscopy (SEM), which revealed the formation of particles with mean diameters at the nanoscale (D[3,2] = 0.135 μm), with a spherical shape, while the dried particles formed larger clusters of several microns (D[3,2] = 80.69 μm). The percentage of the loaded D-limonene was quantified by Thermogravimetric Analysis (TGA), complemented by Gas Chromatography-Mass Spectrometry analysis coupled with a pyrolysis unit (Py/GC-MS). The results showed that the volatiles emitted by the nanoparticles were composed mainly of D-limonene (10% w/w of dry particles). Particles subjected to higher temperatures tended to decompose. The mechanism that governs the release of D-limonene from the as-synthesized particles was studied by fitting mathematical models to the release data obtained by isothermal TGA analysis of the dry particles subjected to accelerated conditions. The analysis revealed a two-stage release of the volatiles, one governed by D-limonene release and the other governed by TEGDMA release. Finally, the antimicrobial potency of the D-limonene-loaded particles was demonstrated, indicating the successful synthesis of polymeric nanoparticles loaded with D-limonene, owing to enhanced antimicrobial properties. The overall performance of these nanoparticles renders them a promising candidate material for the formation of self-sterilized surfaces with enhanced antimicrobial activity and potential application in food packaging.

High Frequency Sonoprocessing: A New Field of Cavitation-Free Acoustic Materials Synthesis, Processing, and Manipulation.

Ultrasound constitutes a powerful means for materials processing. Similarly, a new field has emerged demonstrating the possibility for harnessing sound energy sources at considerably higher frequencies (10 MHz to 1 GHz) compared to conventional ultrasound (⩽3 MHz) for synthesizing and manipulating a variety of bulk, nanoscale, and biological materials. At these frequencies and the typical acoustic intensities employed, cavitation—which underpins most sonochemical or, more broadly, ultrasound‐mediated processes—is largely absent, suggesting that altogether fundamentally different mechanisms are at play. Examples include the crystallization of novel morphologies or highly oriented structures; exfoliation of 2D quantum dots and nanosheets; polymer nanoparticle synthesis and encapsulation; and the possibility for manipulating the bandgap of 2D semiconducting materials or the lipid structure that makes up the cell membrane, the latter resulting in the ability to enhance intracellular molecular uptake. These fascinating examples reveal how the highly nonlinear electromechanical coupling associated with such high‐frequency surface vibration gives rise to a variety of static and dynamic charge generation and transfer effects, in addition to molecular ordering, polarization, and assembly—remarkably, given the vast dimensional separation between the acoustic wavelength and characteristic molecular length scales, or between the MHz‐order excitation frequencies and typical THz‐order molecular vibration frequencies.

Latex particles by emulsion and dispersion polymerizations: sensitization with specific antigens of leptospirosis and application to immunoagglutination

The controlled synthesis of polymer nanoparticles is of great interest in the production of latexes with well defined characteristics. These products can be applied in biomedicine as carriers of biomolecules (e.g. proteins and enzymes), and in particular as latexes for immunoassays used for example in immunoagglutination test, which allow amplify the antigen–antibody reaction, being simple, quick and inexpensive diagnostic tools. The synthesis of polystyrene (PS) latex particles and of core–shell particles, with controlled size distribution, functional groups and surface charge densities is considered here. PS latexes were synthesized in the 100–1100 nm diameter range, by either emulsion or dispersion polymerization. Such latexes were then used as seeds in emulsion copolymerizations of styrene and a functional monomer (methacrylic acid or glycidyl methacrylate), thus producing particles with carboxyl or epoxy functionalities, respectively. Changes in the polymerization recipes employed under batch operation were analyzed. Latex characterization involved measurements of mean particle diameters, the polydispersity index, functional group densities and zeta potential. Finally, latexes were sensitized (by either physical adsorption or covalent coupling) with specific antigens to obtain latex–protein complexes, and one of them was tested as agglutination assay for detecting leptospirosis disease in bovine samples, as an example of the potential application of the latexes produced.

Cross-Linker-Controlled Ostwald Ripening in Emulsion Polymerization of Hollow Copolymer Nanoparticles.

We propose a synthesis method for hollow copolymer nanoparticles, in which the size is controllable by the wettability of the materials designed by relative energy difference (RED). We investigated the influence of cross-linkers in RED and the hollow polymer nanoparticle synthesis. The size of the nanoparticles was characterized by scanning electron microscopy and transmission electron microscopy images. The diameter size of the hollow copolymer (styrene-co-methyl methacrylate) changes from 400 to 141 nm and the average core-vacancy sizes changes from 330 to 71 nm as increasing the feed ratio of the cross-linker, divinyl benzene, from 0.07 to 0.43. Cross-linkers in polymerization precipitates a polymerization reaction to produce seed copolymer particles quickly. The seed copolymer is a more transferrable medium through the surfactants across emulsion droplets and inhibits emulsion growth by unstable concentration variations of seed copolymers in emulsions. Therefore, Ostwald ripening was reduced by a higher feeding ratio of the cross-linker in the copolymer, which tends to produce smaller sized hollow nanoparticles.

Synthesis of polymer nanoparticles via electrohydrodynamic emulsification-mediated self-assembly

HypothesisElectrospray can rapidly produce fine, organic solvent-in-water emulsions in the absence of surfactant via electrohydrodynamic emulsification (EE), a reverse configuration of traditional electrospray. This paper investigates whether EE can produce high-quality nanocomposites comprised of block co-polymers and organic nanoparticles (NPs) via the interfacial instability (IS) self-assembly method. Surfactant-free approaches may increase encapsulation efficiency and product uniformity, process speed, and ease of downstream product purification. ExperimentsAll particles were produced using EE-mediated self-assembly (SA) (EE-SA). Particles were produced using poly(lactic-co-glycolic acid) (PLGA) polymers as proof of concept. Then, block copolymer (BCP) micelles were synthesized from polystyrene-block-poly(ethylene oxide) (PS-b-PEO) (PS 9.5 kDa:PEO 18.0 kDa) in the presence and absence of superparamagnetic iron oxide nanoparticles (SPIONs) or quantum dots (QDs). Encapsulant concentration was varied, and the effect of encapsulant NP ligands on final particle size was investigated. FindingsEE-SA generated both pure polymer NPs and nanocomposites containing SPIONs and QDs. PLGA particles spanned from sub- to super-micron sizes. PS-b-PEO NPs and nanocomposites were highly monodisperse, and more highly loaded than those made via a conventional, surfactant-rich IS process. Free ligands decreased the size of pure BCP particles. Increasing encapsulant levels led to a morphological transition from spherical to worm-like to densely loaded structures.