Ephedra intermedia Schrenk & C. A. Mey Methanol Extract: Nanoencapsulation by Mini-Emulsion Polymerization and its Release Trend under Simulated Conditions of the Human Body.

In this research, the extract of Ephedra intermedia Schrenk & C.A.Mey. was encapsulated using the mini-emulsion polymerization method based on methyl methacrylate polymers with a nanometer size. The encapsulated extract was characterized using different analytical techniques. Furthermore, the loading efficiency and release of the plant extract were examined. FT-IR spectroscopy confirmed the formation of an expectational product. The TEM and SEM imaging showed a spherical morphology for the prepared encapsulated extract. The average size of poly-methyl-methacrylate nanoparticles containing Ephedra extract was found to be approximately 47 nm. The extract loading efficiency and encapsulation efficiency test demonstrated a dose-depending behavior on E. intermedia extract for both analyses, which is highly advantageous for traversing biological barriers. The release assay shows a controlled release for the extract at phosphate buffer solution (PBS). A 38 % release was calculated after 36 hours. The results obtained from the present study reveal that encapsulating the plant extract is a suitable alternative to control and increase their medicinal properties.

Copper Nanodrugs by Atom Transfer Radical Polymerization.

In this study, some copper catalysts used for atom transfer radical polymerization (ATRP) were explored as efficient anti-tumor agents. The aqueous solution of copper-containing nanoparticles with uniform spheric morphology was in situ prepared through a copper-catalyzed activator generated by electron transfer (AGET) ATRP in water. Nanoparticles were then directly injected into tumor-bearing mice for antitumor chemotherapy. The copper nanodrugs had prolonged blood circulation time and enhanced accumulation at tumor sites, thus showing potent antitumor activity. This work provides a novel strategy for precise and large-scale preparation of copper nanodrugs with high antitumor activity.

Nanocarriers with Multiple Cargo Load-A Comprehensive Preparation Guideline Using Orthogonal Strategies.

Multifunctional nanocarriers enhance the treatment efficacy for modern therapeutics and have gained increasing importance in biomedical research. Codelivery of multiple bioactive molecules enables synergistic therapies. Coencapsulation of cargo molecules into one nanocarrier system is challenging due to different physicochemical properties of the cargo molecules. Additionally, coencapsulation of multiple molecules simultaneously shall proceed with high control and efficiency. Orthogonal approaches for the preparation of nanocarriers are essential to encapsulate sensitive bioactive molecules while preserving their bioactivity. Preparation of nanocarriers by physical processes (i.e., self-assembly or coacervation) and chemical reactions (i.e., click reactions, polymerizations, etc.) are considered as orthogonal methods to most cargo molecules. This review shall act as a guideline to allow the reader to select a suitable preparation protocol for a desired nanocarrier system. This article helps to select for combinations of cargo molecules (hydrophilic-hydrophobic, small-macro, organic-inorganic) with nanocarrier material and synthesis protocols. The focus of this article lies on the coencapsulation of multiple cargo molecules into biocompatible and biodegradable nanocarriers prepared by orthogonal strategies. With this toolbox, the selection of a preparation method for a known set of cargo molecules to prepare the desired biodegradable and loaded nanocarrier shall be provided.

LipNanoCar Technology - A Versatile and Scalable Technology for the Production of Lipid Nanoparticles.

The extensive knowledge in the miniemulsion technique used in biocatalysis applications by the authors allowed the development of drug delivery systems that constitutes the LipNanoCar technology core for the production of lipid nanoemulsions and solid lipid nanoparticles. The LipNanoCar technology, together with adequate formulations of different oils, fatty acids, surfactants, and temperature, allows the entrapment of several bioactive and therapeutic compounds in lipid nanoparticles for cosmetic, nutrition, and pharmaceutical applications.The LIpNanoCar technology allowed lipid nanoparticles production with average sizes ranging from 100 to 300 nm and Zeta Potentials between -55 and -20 mV. Concomitantly, high entrapment or encapsulation efficiencies (%EE) were achieved, as illustrated in this work for ß-carotene and vitamins derivatives (>85%) for cosmetic application, and for antibiotics currently used in chemotherapy, like rifampicin (69-85%) and pyrazinamide (14-29%) against Mycobacterium tuberculosis (TB), and ciprofloxacin (>65%) and tobramycin (~100%) in Cystic Fibrosis (CF) respiratory infections therapy. Ciprofloxacin presented, for example, a quick-release from the lipid nanoparticles using a dialysis tubing (96% in the first 7 h), but slower than the free antibiotic (95% in the first 3 h). This result suggests that ciprofloxacin is loaded near the external surface of the lipid nanoparticles.The toxicity and validation of entrapment of antibiotics in lipid nanoparticles for Cystic Fibrosis therapy were assessed using Caenorhabditis elegans as an animal model of bacterial infection. Fluorescence microscopy of an entrapped fluorescent dye (DiOC) confirmed the uptake of the lipid nanoparticles by ingestion, and their efficacy was successfully tested in C. elegans. Burkholderia contaminans IST408 and Burkholderia cenocepacia K56-2 infections were tested as model bacterial pathogens difficult to eradicate in Cystic Fibrosis respiratory diseases.

Larvicidal Effect of Hyptis suaveolens (L.) Poit. Essential Oil Nanoemulsion on Culex quinquefasciatus (Diptera: Culicidae).

Mosquitoes can be vectors of pathogens and transmit diseases to both animals and humans. Species of the genus Culex are part of the cycle of neglected diseases, especially Culex quinquefasciatus, which is an anthropophilic vector of lymphatic filariasis. Natural products can be an alternative to synthetic insecticides for vector control; however, the main issue is the poor water availability of some compounds from plant origin. In this context, nanoemulsions are kinetic stable delivery systems of great interest for lipophilic substances. The objective of this study was to investigate the larvicidal activity of the Hyptis suaveolens essential oil nanoemulsion on Cx. quinquefasciatus. The essential oil showed a predominance of monoterpenes with retention time (RT) lower than 15 min. The average size diameter of the emulsions (sorbitan monooleate/polysorbate 20) was ≤ 200 nm. The nanoemulsion showed high larvicidal activity in concentrations of 250 and 125 ppm. CL50 values were 102.41 (77.5253−149.14) ppm and 70.8105 (44.5282−109.811) ppm after 24 and 48 h, respectively. The mortality rate in the surfactant control was lower than 9%. Scanning micrograph images showed changes in the larvae's integument. This study achieved an active nanoemulsion on Cx. quinquefasciatus through a low-energy-input technique and without using potentially toxic organic solvents. Therefore, it expands the scope of possible applications of H. suaveolens essential oil in the production of high-added-value nanosystems for tropical disease vector control.

Plant Oil-Based Acrylic Latexes towards Multisubstrate Bonding Adhesives Applications.

To investigate the utility of acrylic monomers from various plant oils in adhesives manufacturing, 25-45 wt. % of high oleic soybean oil-based monomer (HOSBM) was copolymerized in a miniemulsion with commercially applied butyl acrylate (BA), methyl methacrylate (MMA), or styrene (St). The compositions of the resulting ternary latex copolymers were varied in terms of both "soft" (HOSBM, BA) and "rigid" (MMA or St) macromolecular fragments, while total monomer conversion and molecular weight of copolymers were determined after synthesis. For most latexes, results indicated the presence of lower and higher molecular weight fractions, which is beneficial for the material adhesive performance. To correlate surface properties and adhesive performance of HOSBM-based copolymer latexes, contact angle hysteresis (using water as a contact liquid) for each latex-substrate pair was first determined. The data showed that plant oil-based latexes exhibit a clear ability to spread and adhere once applied on the surface of materials differing by polarities, such as semicrystalline polyethylene terephthalate (PET), polypropylene (PP), bleached paperboard (uncoated), and tops coated with a clay mineral paperboard. The effectiveness of plant oil-based ternary latexes as adhesives was demonstrated on PET to PP and coated to uncoated paperboard substrates. As a result, the latexes with high biobased content developed in this study provide promising adhesive performance, causing substrate failure instead of cohesive/adhesive break in many experiments.

Liquid-Crystalline Polymer Particles Prepared by Classical Polymerization Techniques.

Liquid-crystalline polymer particles prepared by classical polymerization techniques are receiving increased attention as promising candidates for use in a variety of applications including micro-actuators, structurally colored objects, and absorbents. These particles have anisotropic molecular order and liquid-crystalline phases that distinguish them from conventional polymer particles. In this minireview, the preparation of liquid-crystalline polymer particles from classical suspension, (mini-)emulsion, dispersion, and precipitation polymerization reactions are discussed. The particle sizes, molecular orientations, and liquid-crystalline phases produced by each technique are summarized and compared. We conclude with a discussion of the challenges and prospects of the preparation of liquid-crystalline polymer particles by classical polymerization techniques.

Antimicrobial Activity of Cationic Poly(3-hexylthiophene) Nanoparticles Coupled with Dual Fluorescent and Electrochemical Sensing: Theragnostic Prospect.

Designing therapeutic and sensor materials to diagnose and eliminate bacterial infections remains a significant challenge for active theragnostic nanoprobes. In the present work, fluorescent/electroactive poly(3-hexylthiophene) P3HT nanoparticles (NPs) stabilized with quaternary ammonium salts using cetyltrimethylammonium bromide (CTAB), (CTAB-P3HT NPs) were prepared using a simple mini-emulsion method. The morphology, spectroscopic properties and electronic properties of CTAB-P3HT NPs were characterized by DLS, zeta potential, SEM, TEM, UV-vis spectrophotometry, fluorescence spectroscopy and electrochemical impedance spectroscopy (EIS). In an aqueous solution, CTAB-P3HT NPs were revealed to be uniformly sized, highly fluorescent and present a highly positively charged NP surface with good electroactivity. Dual detection was demonstrated as the binding of the bacteria to NPs could be observed by fluorescence quenching as well as by the changes in EIS. Binding of E. coli to CTAB-P3HT NPs was demonstrated and LODs of 5 CFU/mL and 250 CFU/mL were obtained by relying on the fluorescence spectroscopy and EIS, respectively. The antimicrobial activity of CTAB-P3HT NPs on bacteria and fungi was also studied under dark and nutritive conditions. An MIC and an MBC of 2.5 µg/mL were obtained with E. coli and with S. aureus, and of 0.312 µg/mL with C. albicans. Additionally a good biocompatibility toward normal human cells (WI38) was observed, which opens the way to their possible use as a therapeutic agent.

Low-Temperature Miniemulsion-Based Routes for Synthesis of Metal Oxides.

The use of miniemulsions containing chemical precursors in the disperse phase is a versatile method to produce nanoparticles and nanostructures of different chemical nature, including not only polymers, but also a variety of inorganic materials. This Minireview focuses on materials in which nanostructures of metal oxides are synthesized in processes that involve the miniemulsion technique in any of the steps. This includes in the first place those approaches in which the spaces provided by nanodroplets are directly used to confine precipitation reactions that lead eventually to oxides. On the other hand, miniemulsions can also be used to form functionalized polymer nanoparticles that can serve either as supports or as controlling agents for the synthesis of metal oxides. Herein, the description of essential aspects of the methods is combined with the most representative examples reported in the last years for each strategy.

Preparation of Methacrylate Polymer/Reduced Graphene Oxide Nanocomposite Particles Stabilized by Poly(ionic liquid) Block Copolymer via Miniemulsion Polymerization.

Poly(n-butyl methacrylate) (PnBMA)/reduced graphene oxide (rGO) nanocomposite films are prepared using two different routes. The first route involves preparation of PnBMA nanoparticles containing homogeneously dispersed rGO nanosheets by miniemulsion polymerization using a block copolymer of ionic liquid (IL) monomer and nBMA. The IL units act as adsorption sites for rGO whereas BMA units provide solubility in the BMA monomer droplets. Nanocomposite films obtained from miniemulsion polymerization exhibit higher tensile modulus in comparison with the films prepared by mixing a PnBMA emulsion and aqueous graphene oxide (GO) dispersion. The second route involves preparation of PnBMA particles armored with rGO nanosheets via miniemulsion polymerization using the same poly(ionic liquid) (PIL) block copolymer. An anionic exchange reaction is conducted to obtain more hydrophilic PIL units in the block copolymer, thus providing adsorption sites of GO nanosheets at the interface of the polymer particles. Subsequent chemical reduction of GO to rGO using hydrazine monohydrate results in formation of a PnBMA/rGO nanocomposite. The resulting nanocomposite film exhibits electrical conductivity (2.0 × 10-3 S m-1).

Redox-Initiated Reversible Addition-Fragmentation Chain Transfer (RAFT) Miniemulsion Polymerization of Styrene using PPEGMA-Based Macro-RAFT Agent.

Redox-initiated reversible addition-fragmentation chain transfer (RAFT) miniemulsion polymerizations are successfully conducted with an employment of trithiocarbonate-based macro-RAFT agents and surfactant. Two macro-RAFT agents-hydrophilic poly(poly(ethylene glycol) methyl ether methacrylate) (PPEGMA27 ) and amphiphilic poly(poly(ethylene glycol) methyl ether methacrylate)-b-polystyrene (PPEGMA27 -b-PS33 )- are examined for the miniemulsion polymerization of styrene. The use of PPEGMA27 (in the presence of sodium dodecyl sulfate (SDS)) results in a slow polymerization rate with a broad particle size. In the absence of SDS, the use of PPEGMA27 -b-PS33 results in a broad particle size distribution due to its inability to form uniform initial droplets whereas the same amphiphilic block copolymer in the presence of SDS yields resulting products with a uniform particle size distribution. The latter exhibits a fashion of controlled polymerization with a high consumption of monomer (98% in 100 min) and a narrow molecular weight distribution throughout the polymerization. This is attributed to the formation of uniform droplets facilitated by SDS in a miniemulsion. The amphiphilic macro-RAFT agent is able to anchor efficiently on the monomer droplet or particle/water interface and form stabilized particles of well-defined PPEGMA27 -b-PS block copolymer, confirmed using dynamic light scattering and transmission electron micrographs.

Catalytic Halogen Exchange in Miniemulsion ARGET ATRP: A Pathway to Well-Controlled Block Copolymers.

Halogen exchange in atom transfer radical polymerization (ATRP) is an efficient way to chain-extend from a less active macroinitiator (MI) to a more active monomer. This has been previously achieved by using CuCl/L in the equimolar amount to Pn -Br MI in the chain extension step. However, this approach cannot be effectively applied in systems based on regeneration of activators (ARGET ATRP), since they operate with ppm amounts of catalysts. Herein, a catalytic halogen exchange procedure is reported using a catalytic amount of Cu in miniemulsion ARGET ATRP to chain-extend from a less active poly(n-butyl acrylate) (PBA) MI to a more active methyl methacrylate (MMA) monomer. Influence of different reagents on the initiation efficiency and dispersity is studied. Addition of 0.1 m NaCl or tetraethylammonium chloride to ATRP of MMA initiated by methyl 2-bromopropionate leads to high initiation efficiency and polymers with low dispersity. The optimized conditions are then employed in chain extension of PBA MI with MMA to prepare diblock and triblock copolymers.

Immobilization of lipase Eversa Transform 2.0 on poly(urea-urethane) nanoparticles obtained using a biopolyol from enzymatic glycerolysis.

In this work, the free lipase Eversa® Transform 2.0 was used as a catalyst for enzymatic glycerolysis reaction in a solvent-free system. The product was evaluated by nuclear magnetic resonance (1H NMR) and showed high conversion related to hydroxyl groups. In sequence, the product of the glycerolysis was used as stabilizer and biopolyol for the synthesis of poly(urea-urethane) nanoparticles (PUU NPs) aqueous dispersion by the miniemulsion polymerization technique, without the use of a further surfactant in the system. Reactions resulted in stable dispersions of PUU NPs with an average diameter of 190 nm. After, the formation of the PUU NPs in the presence of concentrated lipase Eversa® Transform 2.0 was studied, aiming the lipase immobilization on the NP surface, and a stable enzymatic derivative with diameters around 231 nm was obtained. The hydrolytic enzymatic activity was determined using ρ-nitrophenyl palmitate (ρ-NPP) and the immobilization was confirmed by morphological analysis using transmission electron microscopy and fluorescence microscopy.

Modular Approach for the Design of Smart Polymeric Nanocapsules.

The formation of nanocapsules from a modular perspective for self-assembled nanocapsules, so-called polymersomes, and nanocapsules with a covalently formed shell are discussed in this review. It is shown that there are common and comparable ways for the selective and controlled release of payloads for stimuli-responsive systems and nanocapsule functionalization in order to use them for drug delivery and diagnostic applications.

Synthesis of Diblock and Triblock Polymers from Cyclooctadiene and Norbornene Via ROMP in Miniemulsion.

The synthesis of diblock and triblock linear polyolefins via ring opening metathesis polymerization (ROMP) in an aqueous nanoparticle dispersion is presented. The different block polyolefins are synthesized from the cyclic olefins 1,5-cyclooctadiene and norbornene (NB), using a water-soluble TEGylated ruthenium alkylidene catalyst, yielding the structures PCOD-b-PNB, PNB-b-PCOD, and PCOD-b-PNB-b-PCOD. High monomer conversion (>90%), monitored by NMR, is achieved in relatively short times (≈1 h) for the polymerization of each block. The livingness of the system, essential to obtain block copolymers, is confirmed by gel permeation chromatography. Latex particles' size during the multiple steps range between 90 and 150 nm. The results demonstrate that it is possible to obtain nanoparticle latexes from ROMP-based monomers with block copolymer architectures, creating the opportunity to copolymerize olefins bearing different functional groups for the synthesis of new materials.

Linker-protein G mediated functionalization of polystyrene-encapsulated upconversion nanoparticles for rapid gene assay using convective PCR.

The authors report on a simplified approach to encapsulate upconversion nanoparticles (UCNPs) in polystyrene spheres by mini-emulsion polymerisation. The resulting particles (PS-UCNP) are hydrophilic, stable and suitable for biomolecular recognition and biosensing applications. Also, a strategy was developed for bioconjugation of antibodies onto the surface of the PS-UCNPs by using the bifunctional fusion protein linker-protein G (LPG). LPG mediates the functionalisation of PS-UCNPs with antibodies against digoxigenin allowing for specific labelling of convective PCR (cPCR) amplicons. Lambda DNA was amplified using cPCR on a heat block for 30 min using the digoxigenin labelled forward and biotin labelled reverse primers. The antibody functionalised PS-UCNPs bind to the digoxigenin end of the cPCR amplicons. Finally, the streptavidin labelled magnetic beads were used to selectively capture the PS-UCNP-labelled cPCR amplicons and the upconversion signal was detected at 537 nm under 980 nm excitation. This sandwich approach enables direct recognition of the target lambda DNA with a detection limit of 103 copies µL-1. The upconversion signal decreased proportionally to the concentration of the lambda DNA with a linear response between 107 and 103 copies of DNA. Graphical abstract Schematic representation of polystyrene-encapsulated upconversion nanoparticles (PS-UCNPs) prepared by mini-emulsion polymerisation. The PS-UCNPs were functionalised with anti-digoxigenin antibody using the fusion protein linker-protein G (LPG). Detection of digoxigenin-labelled amplicons is achieved (a) by using the antibody-functionalised LPG@PS-UCNP labels; (b) magnetic separation, and (c) 980 nm laser light for detection of the green upconversion luminescence peaking at 537 nm.

Synthesis of high payload nanohydrogels for the ecapsulation of hydrophilic molecules via inverse miniemulsion polymerization: caffeine as a case study.

The association of an active principle with a nanocarrier is known to improve its stability and protect it from external factors. Nevertheless, loading of nanoparticles with highly hydrophilic substances like caffeine remains a tricky issue. In the present study, inverse miniemulsion systems were successfully coupled to UV radiation to synthesize polymeric nanohydrogels for drug delivery. The proper choice of the continuous and dispersed phase chemical composition led to the entrapment of active principle into the miniemulsion droplets. Our confinement-based strategy enabled unprecedented caffeine encapsulation efficiency inside 100-nm particles. Dimensional, thermal, and spectroscopic characterizations were carried out to investigate both unloaded and loaded nanohydrogels. Furthermore, in vitro release studies evaluated caffeine release kinetics from nanohydrogels by means of dialysis tests. It was demonstrated that controlled and sustained release occurred within the first 50 hours. Experimental data were found to fit the Higuchi model suggesting that the active principle release is diffusion controlled.

Increased in vitro leishmanicidal activity of octyl gallate loaded poly(methyl methacrylate) nanoparticles.

The current paucity of effective and affordable drugs for the treatment of leishmaniasis renders the search for new therapeutic alternatives a priority. Gallic acid-related compounds display anti-parasitic activities and their incorporation into drug carrier systems, such as polymeric nanoparticles may be a viable alternative for leishmaniasis treatment. Therefore, this study focused on the synthesis and characterization of octyl gallate (G8) loaded poly(methyl methacrylate) (PMMA) nanoparticles via miniemulsion polymerization in order to increase the leishmanicidal activity of this compound. G8 loaded PMMA nanoparticles presented a spherical morphology with a mean size of 108 nm, a negatively charged surface (-33 ± 5 mV) and high encapsulation efficiency (83% ± 5). Fourier-transform infrared spectroscopy and X-ray diffraction analysis confirmed that G8 was encapsulated in PMMA nanoparticles and presented a biphasic release profile. The G8 loaded PMMA nanoparticles did not present cytotoxic effect on human red blood cells. G8 loaded PMMA nanoparticles displayed a leishmanicidal activity almost three times higher than free G8 while the cytotoxic activity against human THP-1 cells remained unchanged.

Optimization and characterization of high pressure homogenization produced chemically modified starch nanoparticles.

Chemically modified starch (RS4) nanoparticles were synthesized through homogenization and water-in-oil mini-emulsion cross-linking. Homogenization was optimized with regard to z-average diameter by using a three-factor-three-level Box-Behnken design. Homogenization pressure (X1), oil/water ratio (X2), and surfactant (X3) were selected as independent variables, whereas z-average diameter was considered as a dependent variable. The following optimum preparation conditions were obtained to achieve the minimum average size of these nanoparticles: 50 MPa homogenization pressure, 10:1 oil/water ratio, and 2 g surfactant amount, when the predicted z-average diameter was 303.6 nm. The physicochemical properties of these nanoparticles were also determined. Dynamic light scattering experiments revealed that RS4 nanoparticles measuring a PdI of 0.380 and an average size of approximately 300 nm, which was very close to the predicted z-average diameter (303.6 nm). The absolute value of zeta potential of RS4 nanoparticles (39.7 mV) was higher than RS4 (32.4 mV), with strengthened swelling power. X-ray diffraction results revealed that homogenization induced a disruption in crystalline structure of RS4 nanoparticles led to amorphous or low-crystallinity. Results of stability analysis showed that RS4 nanosuspensions (particle size) had good stability at 30 °C over 24 h.

Ultrastable Liquid-Liquid Interface as Viable Route for Controlled Deposition of Biodegradable Polymer Nanocapsules.

Liquid-liquid interfaces are highly dynamic and characterized by an elevated interfacial tension as compared to solid-liquid interfaces. Therefore, they are gaining an increasing interest as viable templates for ordered assembly of molecules and nanoparticles. However, liquid-liquid interfaces are more difficult to handle compared to solid-liquid interfaces; their intrinsic instability may affect the assembly process, especially in the case of multiple deposition. Indeed, some attempts have been made in the deposition of polymer multilayers at liquid-liquid interfaces, but with limited control over size and stability. This study reports on the preparation of an ultrastable liquid-liquid interface based on an O/W secondary miniemulsion and its possible use as a template for the self-assembly of polymeric multilayer nanocapsules. Such polymer nanocapsules are made of entirely biodegradable materials, with highly controlled size-well under 200 nm-and multi-compartment and multifunctional features enriching their field of application in drug delivery, as well as in other bionanotechnology fields.