Entrapment Of Nanoparticles Research Articles

Entrapment of lipid nanoparticles in peripheral endosomes but not lysosomes impairs intracellular trafficking and endosomal escape

The uptake and intracellular trafficking of lipid nanoparticles (LNPs) along the endolysosomal pathway leading to releasing compartments is critical for delivery efficiency. How the players of the processes interact with each other to affect LNP delivery remains unclear. Here, we employed a recently developed, highly sensitive LNP labeling platform in combination with known-state of endolysosomal activity of cells to address this outstanding question with spatiotemporal analysis. We found the endolysosomal activity (endolyosomal pH, endolysosomal protease activation), which was regulated by nutrients, determines the active endocytosis activity of cells. Elevated internalization of DNA and LNP alike by cells correlated with increased endolysosomal activity. Similar to naked DNA, elevated internalization of LNP resulted in entrapment of LNPs in peripheral endosomes, which significantly impaired the intracellular trafficking of LNP to the perinuclear lysosome region and cytosolic release of LNP cargo. On the other hand, we found the extent of perinuclear lysosomal LNP accumulation positively correlated with the level of transgene expression. Moreover, we found continuous internalization of LNP was necessary not only to saturate the degradation compartments to overcome rapid degradation of LNP but also to maintain a necessary pool of releasing compartments, shuttling between peripheral endosomes and lysosomes via anterograde transport and retrograde transport along microtubules respectively, for meaningful endosomal release. Our results suggest the balance between endocytosis and intracellular trafficking needs to be fine-tuned according to endolysosomal activity of target cell to achieve optimal cytosol release.

Supramolecular Nano‐Grid Platform to Load and Deliver Liposomes and Exosomes

In general, carriers are designed to deliver pharmaceutical (featuring small drug‐molecules) and biopharmaceutical (featuring large‐molecule drugs, e.g., antibodies, proteins, etc.) active ingredients and platform that is capable of transporting nanoparticles is rare. Herein, the fabrication of a supramolecular carrier with a nano‐grid structure for the entrapment of liposomes and exosomes is reported. The nano‐grid particles (NGP) are made of cyclodextrins as elementary units which are widely used to load drugs through host–guest inclusion complexes, whilst its secondary structure further formed the NGP tertiary architectures, enabling the entrapment of nanoparticles. The NGP features stimuli responsiveness, tunable surface charge, and good biocompatibility. The entrapped liposomes in NGP present enhanced distribution in lungs and extended duration of action in mice. And elongated release profiles for over 14 days is obtained for exosomes—making one‐of‐its‐kind unique platform to load and deliver nanoparticles.

Encapsulation of Diosgenin in chitosan nanoparticles with enhanced invitro and invivo anticancer activity in Female Sprague Dawley rats

The main purpose of this study was to optimize the conditions for synthesizing diosgenin-encapsulated chitosan nanoparticles (DIO@CS NPs) and anticancer activity. Nanoparticles encapsulating diosgenin were synthesized using ionic gelation utilizing three different chitosan weight percentages and polyanion STPP (Sodium tripolyphosphate) as the cross-linking agent. The synthesis depended on ionic interaction between positively charged chitosan and negatively charged STPP. The incorporation of diosgenin into the chitosan nanoparticles was verified by Fourier transform infrared spectroscopy (FTIR). Chitosan nanoparticle entrapment effectiveness (EE%) was between 76% to 94% and increased with diosgenin concentration. Invitro diosgenin drug release from nanoparticles was decelerated when employing greater molecular weight chitosan. Chitosan nanoparticles released diosgenin diffusion-controlled in drug release study. DIO@CS nanoparticles evaluated on A431 human skin cancer cells demonstrated significant anticancer activity. These results suggest that DIO@CS NPs could be a novel skin cancer therapy. Each rat received 25 mg/kg DMBA subcutaneously. Tumor-bearing animals were lighter. DMBA-induced mice gained less weight than DIO@CS NPs. Oral DIO@CS NPs (2.5 mg/kg b.wt) recovered cellular antioxidants and mitigated histopathological staining of hematoxylin and eosin on breast carcinoma. Based on the foregoing results, Diosgenin nanoformulations provide a novel breast cancer treatment.

Generating porous metal surfaces as a mean to incorporate thymol-loaded nanoparticles

Porous metals have gained interest in many fields such as biomedicine, electronics, and energy. Despite the many benefits that these structures may offer, one of the major challenges in utilizing porous metals is to incorporate active compounds, either small molecules or macromolecules, on these surfaces. Coatings that contain active molecules have previously been used for biomedical applications to enable the slow release of drugs, e.g., with drug-eluting cardiovascular stents. However, direct deposition of organic materials on metals by coatings is very difficult due to the challenge of obtaining uniform coatings, as well as issues related to layer adherence and mechanical stability. Our study describes an optimization of a production process of different porous metals, aluminum, gold, and titanium, using wet-etching. Pertinent physicochemical measurements were carried out to characterize the porous surfaces. Following the production of porous metal surface, a new methodology for incorporating active materials onto the metals by using mechanical entrapment of polymeric nanoparticles in metal pores was developed. To demonstrate our concept of active material incorporation, we produced an odor-releasing metal object with embedded particles loaded with thymol, an odoriferous molecule. Polymer particles were placed inside nanopores in a 3D-printed titanium ring. Chemical analysis, followed by smell tests, indicated that the smell intensity lasts significantly longer in the porous material containing the nanoparticles, compared with the free thymol.

One-pot synthesis of magnetic N-doped mesoporous carbons as an efficient adsorbent for Ag(I) removal

An efficient strategy was proposed to fabricate magnetic N-doped mesoporous carbons (Fe0/NMC) via one-pot process. This one-pot strategy involved the synthesis of N-containing porous polymers using amphiphilic triblock copolymer (F127) through self-assembly of melamine formaldehyde resin, and the formation and entrapment of Fe0 nanoparticles by an in-situ carbothermal reduction approach. The surface morphology and the main chemical groups of the developed Fe0/NMC were characterized by various analytical methods such as XRD, FTIR, TGA-DTA, BET, TEM and VSM. Fe0/NMC exhibited a mesoporous structure and Fe0 nanoparticles were dispersed homogeneously on Fe0/NMC, with a saturation magnetization of 134.6 emu/g. As an adsorbent, Fe0/NMC showed an excellent adsorption capacity for Ag (I), reaching 335 mg/g. The adsorption process was consistent with the quasi-secondary kinetic model and Freundlich isothermal adsorption model, which indicated that the adsorption process was multilayer adsorption and the adsorbed element Ag was present on Fe0/NMC in the form of Ag(I) as well as chelates and Ag monomers. It could be believed that Fe0/NMC was a viable adsorption material for Ag(I) and had full-scale applications.

PH-responsive chitosan/acrylamide/gold/nanocomposite supported with silver nanoparticles for controlled release of anticancer drug

In this study, we prepared a pH-responsive nanocomposite hydrogel based on chitosan grafted with acrylamide monomer and gold nanoparticles using gamma irradiation method (Cs-g-PAAm/AuNPs). The nanocomposite was enhanced with a layer coating of silver nanoparticles to improve the controlled release of the anticancer drug fluorouracil while increasing antimicrobial activity and decreasing the cytotoxicity of silver nanoparticles in nanocomposite hydrogel by combining with gold nanoparticles to enhance the ability to kill a high number of liver cancer cells. The structure of the nanocomposite materials was studied using FTIR spectroscopy and XRD patterns, which demonstrated the entrapment of gold and silver nanoparticles within the prepared polymer matrix. Dynamic light scattering data revealed the presence of gold and silver in the nanoscale with the polydispersity indexes in the mid-range values, indicating that distribution systems work best. Swelling experiments at various pH levels revealed that the prepared Cs-g-PAAm/Au–Ag-NPs nanocomposite hydrogels were highly responsive to pH changes. Bimetallic pH-responsive Cs-g-PAAm/Au–Ag-NPs nanocomposites exhibit strong antimicrobial activity. The presence of AuNPs reduced the cytotoxicity of AgNPs while increasing their ability to kill a high number of liver cancer cells.Cs-g-PAAm/Au–Ag-NPs has a high amount of fluorouracil drug loaded at pH 7.4 reaching 95 mg/g with a maximum drug release of 97% within 300 min. Cs-g-PAAm/Au–Ag-NPs have been recommended to use as oral delivery of anticancer drugs because they secure the encapsulated drug in the acidic medium of the stomach and release it in the intestinal pH.

Development of a cationic polyethyleneimine-poly(lactic-co-glycolic acid) nanoparticle system for enhanced intracellular delivery of biologics.

Intracellular delivery of proteins, peptides and biologics is an emerging field which has the potential to provide novel opportunities to target intracellular proteins, previously deemed 'undruggable'. However, the delivery of proteins intracellularly remains a challenge. Here, we present a cationic nanoparticle delivery system for enhanced cellular delivery of proteins through use of a polyethyleneimine and poly-(lactic-co-glycolic acid) polymer blend. Cationic nanoparticles were shown to provide increased cellular uptake compared to anionic and neutral nanoparticles, successfully delivering Variable New Antigen Receptors (vNARs), entrapped within the nanoparticle core, to the cell interior. vNARs were identified as ideal candidates for nanoparticle entrapment due to their remarkable stability. The optimised 10% PEI-PLGA nanoparticle formulation displayed low toxicity, was uniform in size and possessed appropriate cationic charge to limit cellular toxicity, whilst being capable of escaping the endo/lysosomal system and delivering their cargo to the cytosol. This work demonstrates the ability of cationic nanoparticles to facilitate intracellular delivery of vNARs, novel biologic agents with potential utility towards intracellular targets.

Entrapment and Voltage-Driven Reorganization of Hydrophobic Nanoparticles in Planar Phospholipid Bilayers.

Engineered nanoparticles (NPs) possess diverse physical and chemical properties, which make them attractive agents for targeted cellular interactions within the human body. Once affiliated with the plasma membrane, NPs can become embedded within its hydrophobic core, which can limit the intended therapeutic functionality and affect the associated toxicity. As such, understanding the physical effects of embedded NPs on a plasma membrane is critical to understanding their design and clinical use. Here, we demonstrate that functionalized, hydrophobic gold NPs dissolved in oil can be directly trapped within the hydrophobic interior of a phospholipid membrane assembled using the droplet interface bilayer technique. This approach to model membrane formation preserves lateral lipid diffusion found in cell membranes and permits simultaneous imaging and electrophysiology to study the effects of embedded NPs on the electromechanical properties of the bilayer. We show that trapped NPs enhance ion conductance and lateral membrane tension in 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and 1,2-diphytanoyl-sn-glycero-3-phosphocholine (DPhPC) bilayers while lowering the adhesive energy of the joined droplets. Embedded NPs also cause changes in bilayer capacitance and area in response to applied voltage, which are nonmonotonic for DOPC bilayers. This electrophysical characterization can reveal NP entrapment without relying on changes in membrane thickness. By evaluating the energetic components of membrane tension under an applied potential, we demonstrate that these nonmonotonic, voltage-dependent responses are caused by reversible clustering of NPs within the unsaturated DOPC membrane core; aggregates form spontaneously at low voltages and are dispersed by higher transmembrane potentials of magnitude similar to those found in the cellular environment. These findings allow for a better understanding of lipid-dependent NP interactions, while providing a platform to study relationships between other hydrophobic nanomaterials and organic membranes.

Entrapment of magnetic nanoparticles into poly(divinylbenzene-co-N-vinylpyrrolidone) copolymer for the determination of prohibited and restricted fragrance ingredients in cosmetic products

In this work, a magnetic composite made by cobalt ferrite (CoFe2O4) magnetic nanoparticles entrapped into a poly(divinylbenzene-co-N-vinylpyrrolidone) copolymer is used to determine recently prohibited and restricted fragrances (i.e., Lilial, Lyral, and methyl-N-methylanthranilate) in cosmetics. This hydrophilic-lipophilic balance type material was characterized by magnetism measurements, scanning electron microscopy, nitrogen adsorption–desorption isotherms, and thermogravimetric analysis. The proposed method is based on stir bar sorptive dispersive microextraction (SBSDME) followed by gas chromatography coupled to mass spectrometry (GC–MS). The main quantitative parameters involved in the SBSDME were optimized by using a Box-Behnken design, whereas the desorption solvent was optimized by using a Simplex-Centroid design. Under the optimized conditions, good analytical features were obtained, showing good linearity (at least up to 200 ng mL−1), enrichment factors from 18 to 26, method limits of detection in the low µg/g range (0.01–0.1 µg g−1), and good intra- and inter-day repeatability (relative standard deviations below 10 %). Matrix effects were negligible as long as no more than 0.1 and 0.25 g of fat- and water-soluble samples, respectively, were weighed and diluted to 25 mL. Finally, the proposed method was successfully applied to three commercial cosmetic samples of different formulation, and quantitative relative recovery values (76–108 %) were obtained by external calibration. This work expands the analytical potential of SBSDME to the use of new magnetic polymer-based sorbents. In addition, it contributes to the availability of methods to ensure the safety of cosmetic products through quality control by means of a green methodology.

Aloe Vera Functionalized Magnetic Nanoparticles Entrapped Ca Alginate Beads as Novel Adsorbents for Cu(II) Removal from Aqueous Solutions.

CABs (Ca alginate beads), AVCABs (Aloe vera Ca alginate beads), and AVMNCABs (Aloe-vera functionalized magnetic nanoparticles entrapped Ca alginate beads) were developed as adsorbents for the removal of Cu(II) from aqueous solutions. The materials were characterized using Fourier-transform infrared (FTIR) spectroscopy, high-resolution scanning electron microscopic (HR-SEM) analysis, X-ray diffraction (XRD), energy-dispersive X-ray (EDX) spectroscopy, and a vibrating-sample magnetometer (VSM). The effect of several parameters, such as pH, time, temperature, adsorbent dose, etc., were investigated. The adsorption isotherm of Cu(II) was adjusted best to the Langmuir model. The maximum adsorption capacities were 111.11 mg/g, 41.66 mg/g, and 15.38 mg/g for AVMNCABs, AVCABs, and CABs, respectively. The study of the adsorption kinetics for Cu(II) ions on beads followed a pseudo-second-order kinetic model, with a very good correlation in all cases. The adsorption studies used a spectrophotometric method, dealing with the reaction of Cu(II) with KSCN and variamine blue.

Penetration and aerosolization of cough droplet spray through face masks: A unique pathway of transmission of infection

The advent of the COVID-19 pandemic has necessitated the use of face masks, making them an integral part of the daily routine. Face masks occlude the infectious droplets during any respiratory event contributing to source control. In the current study, spray impingement experiments were conducted on porous surfaces like masks having a different porosity, pore size, and thickness. The spray mimics actual cough or a mild sneeze with respect to the droplet size distribution (20–500 μm) and velocity scale (0–14 m/s), which makes the experimental findings physiologically realistic. The penetration dynamics through the mask showed that droplets of all sizes beyond a critical velocity penetrate through the mask fabric and atomize into daughter droplets in the aerosolization range, leading to harmful effects due to the extended airborne lifetime of aerosols. By incorporating spray characteristics along with surface tension and viscous dissipation of the fluid passing through the mask, multi-step penetration criteria have been formulated. The daughter droplet size and velocity distribution after atomizing through multi-layered masks and its effects have been discussed. Moreover, the virus-emulating particle-laden surrogate respiratory droplets are used in impingement experiments to study the filtration and entrapment of virus-like nanoparticles in the mask. Furthermore, the efficacy of the mask from the perspective of a susceptible person has been investigated.

Conjugation of Oligo-His Peptides to Magnetic γ-Fe2O3@SiO2 Core-Shell Nanoparticles Promotes Their Access to the Cytosol.

The endosomal entrapment of functional nanoparticles is a severe limitation to their use for biomedical applications. In the case of magnetic nanoparticles (MNPs), this entrapment leads to poor heating efficiency for magnetic hyperthermia and suppresses the possibility to manipulate them in the cytosol. Current strategies to limit their entrapment include functionalization with cell-penetrating peptides to promote translocation directly across the cell membrane or facilitate endosomal escape. However, these strategies suffer from the potential release of free peptides in the cell, and to the best of our knowledge, there is currently a lack of effective methods for the cytosolic delivery of MNPs after incubation with cells. Herein, we report the conjugation of fluorescently labeled cationic peptides to γ-Fe2O3@SiO2 core-shell nanoparticles by click chemistry to improve MNP access to the cytosol. We compare the effect of Arg9 and His4 peptides. On the one hand, Arg9 is a classical cell-penetrating peptide able to enter cells by direct translocation, and on the other hand, it has been demonstrated that sequences rich in histidine residues can promote endosomal escape, possibly by the proton sponge effect. The methodology developed here allows a high colocalization of the peptides and core-shell nanoparticles in cells and confirms that grafting peptides rich in histidine residues onto nanoparticles promotes NPs' access to the cytosol. Endosomal escape was confirmed by a calcein leakage assay and by ultrastructural analysis in transmission electron microscopy. No toxicity was observed for the peptide-nanoparticles conjugates. We also show that our conjugation strategy is compatible with the addition of multiple substrates and can thus be used for the delivery of cytoplasm-targeted therapeutics.

Entrapment of Magnetic Nanoparticles into Poly(Divinylbenzene-Co-N-Vinylpyrrolidone) Copolymer for the Determination of Prohibited and Restricted Fragrance Ingredients in Cosmetic Products

Entrapment of Magnetic Nanoparticles into Poly(Divinylbenzene-Co-N-Vinylpyrrolidone) Copolymer for the Determination of Prohibited and Restricted Fragrance Ingredients in Cosmetic Products

An experimental study on the effect of concentration of green nanoadditives on the tribological properties of the biolubricants

The paper aims to introduce a sustainable solution in the field of lubrication science. A green nano additive, hexagonal boron nitride (h-BN) is mixed with two biofriendly natural oils (avocado oil and hazelnut oil) and the tribological properties of the nanolubricants are evaluated on a four-ball tribotester. The nanoparticles are less than 100 nm in diameter and are added in varying concentrations of 0-1 wt.%. The tribological properties are evaluated as per ASTM D4172 and the stability of the nanoparticles is measured for a period of 24 hours using a double beam spectrophotometer. The UV spectroscopy results indicate the nanoparticles are stable after the sonication process and sediment very less after 24 hours. The antiwear properties of both natural oil improve with the increase in the concentration of h-BN nanoparticles. The maximum improvement in the wear properties is observed at 1 wt.% and is equal to 19.5% and 36.55% for avocado oil and hazelnut oil respectively. The improvement in the antiwear properties are ascribed to the different nanolubrication mechanisms: tribofilm formation, non-direct contact phenomenon, and entrapment of nanoparticles between wear agglomerates.

Influence of molecular interactions on structure, controlled release and cytotoxicity of curcumin encapsulated chitosan - Silica nanostructured microspheres

Curcumin possesses numerous medicinal benefits including anti-cancer and anti-viral properties. However, its wide scale use as a drug is often hindered owing to the dearth of suitable drug-delivery systems which can solubilise it for long-term sustained-release and safeguard its beneficial properties. In this work, a fast, one-step method, employing evaporation induced assembly of colloids, has been employed for the synthesis of curcumin encapsulated organic-inorganic hybrid micron-sized spheres. Detailed physical properties of the microspheres, with scaffolds of silica nanoparticles (∼8.5 nm) cross linked by chitosan, are studied to trace the underlying mechanism of structural assembly in such systems, by tuning the polymer matrix with solubilizing agents, DMSO and Tween 20. A systematic modification in the hydrogen bonding network, conformations and interactions between macromolecules is revealed upon tuning the organic matrix. This in turn is found to control the assembly vis-à-vis the granular morphology, drug entrapment and packing fraction of nanoparticles in the microspheres, which have direct influence on the biological properties. Consequently, the microspheres are found to follow a first order drug release kinetics with a tunable rate constant which follows the ordering of packing fraction of silica nanoparticles in the micro-granules. A sustained curcumin release for a period extending up to 24 h has been achieved. Further studies using human lung and cervical cancer cell lines assert good anti-cancer properties of these nanostructured microspheres in cancer cells, while showing no toxicity towards normal cells. Thus, such hybrid organic-inorganic formulations achieved using multi-component colloidal assembly approach, with enhanced stability against degradation, are promising candidates for future clinical applications of water-insoluble drugs.

Non-Woven Textiles Formed from Contact Drawn Poly(ethylene oxide) Fibers Provide Tunable Filtration and Virucidal Properties via Entrapment of Silver Nanoparticles

Filtering facepiece respirators (FFRs) protect wearers from inhalation of fine particulates and help prevent transmission of airborne viruses. Here, an FFR material is produced by successive deposition of contact drawn poly(ethylene oxide) (PEO) fibers. Fibers are formed by immersing an array of pins in a highly viscous precursor solution of PEO and then rapidly removing the pins such that polymer entanglement occurs, forming multiple liquid bridges that rapidly dry as they extend. Tunable filtration is achieved by varying the number of PEO fiber elongation cycles. Placing the PEO textiles between two woven cotton cloths provides structural support and additional filtration capacity, achieving a maximum filtration efficiency of 95% with a corresponding initial pressure drop of 281 Pa. The entrapment of silver nanoparticles in the PEO fibers imparts virucidal properties to PEO-based textiles, as demonstrated by inactivation of a human coronavirus HCoV-OC43 and influenza A virus inoculum. The ability to tune filtration efficiency to application needs and provide advanced function through entrapment of active materials represents a versatile tool for limiting exposure to airborne particulates and pathogens.

Increasing the Power of Polyphenols through Nanoencapsulation for Adjuvant Therapy against Cardiovascular Diseases

Polyphenols play a therapeutic role in vascular diseases, acting in inherent illness-associate conditions such as inflammation, diabetes, dyslipidemia, hypertension, and oxidative stress, as demonstrated by clinical trials and epidemiological surveys. The main polyphenol cardioprotective mechanisms rely on increased nitric oxide, decreased asymmetric dimethylarginine levels, upregulation of genes encoding antioxidant enzymes via the Nrf2-ARE pathway and anti-inflammatory action through the redox-sensitive transcription factor NF-κB and PPAR-γ receptor. However, poor polyphenol bioavailability and extensive metabolization restrict their applicability. Polyphenols carried by nanoparticles circumvent these limitations providing controlled release and better solubility, chemical protection, and target achievement. Nano-encapsulate polyphenols loaded in food grade polymers and lipids appear to be safe, gaining resistance in the enteric route for intestinal absorption, in which the mucoadhesiveness ensures their increased uptake, achieving high systemic levels in non-metabolized forms. Nano-capsules confer a gradual release to these compounds, as well as longer half-lives and cell and whole organism permanence, reinforcing their effectiveness, as demonstrated in pre-clinical trials, enabling their application as an adjuvant therapy against cardiovascular diseases. Polyphenol entrapment in nanoparticles should be encouraged in nutraceutical manufacturing for the fortification of foods and beverages. This study discusses pre-clinical trials evaluating how nano-encapsulate polyphenols following oral administration can aid in cardiovascular performance.

Entrapment of silver nanoparticles in L-α-phosphatidylcholine/cholesterol-based liposomes mitigates the oxidative stress in human keratinocyte (HaCaT) cells

Encapsulation procedures are used to decrease the contact of toxic nanoparticles with cells; however, this field is still not well explored. Therefore, the aim of this paper was to evaluate the effect of encapsulation of silver nanoparticles in L-α-phosphatidylcholine/cholesterol-based liposomes on a human keratinocyte cell line (HaCaT). The homogenous (PdI = 0.171) spherical (~161 nm diameter) complexes were prepared by thin film hydration with the extrusion method. The UV–Vis scan and Dynamic Light Scattering measurement did not show any “free” silver nanoparticles in solutions, which was confirmed by Transmission Electron Microscope analysis. Moreover, the liposomes were tested on HaCaT cells, showing that the encapsulation process reduced the toxicity by 30%-10% at the 100 nM and 1 pM concentrations, respectively, in comparison to “free” nanoparticles, measured by resazurin reduction and lactate dehydrogenase release assays. Moreover, the caspase-3 activity was lower after 48-h treatment with LipoAgNPs than with AgNPs. The level of reactive oxygen species (ROS) after 1, 6, 48, and 72 h of treatment of HaCaT cells was significantly lower in comparison to cells treated with “bare” silver nanoparticles analyzed with the H2DCF-DA probe. The metabolic activity was strictly correlated with toxicity, indicating a lower negative impact of encapsulated nanoparticles than the “bare” ones.

Entrapment of Macrophage-Target Nanoparticles by Yeast Microparticles for Rhein Delivery in Ulcerative Colitis Treatment.

In this study, we developed an advanced colitis-targeted nanoparticles (NPs)-into-yeast cell wall microparticles (YPs) drug delivery system for ulcerative colitis (UC) therapy. In brief, YPs entrap hyaluronic acid (HA), and polyethylenimine (PEI) modified rhein (RH)-loaded ovalbumin NPs (HA/PEI-RH NPs) to form HA/PEI-RH NYPs. YPs can make HA/PEI-RH NPs pass through gastric environment stably and be degraded by β-glucanase to promote drug release from HA/PEI-RH NYPs in the colon. Cellular uptake evaluation confirmed that HA/PEI-RH NPs could specifically target and enhance the uptake rate via HA ligands. In biodistribution studies, HA/PEI-RH NYPs were able to efficiently accumulate in the inflammed colon in mice. In vivo experiments revealed that the HA/PEI-RH NYPs could significantly alleviate inflammation by inhibiting the TLR4/MyD88/NF-κB signaling pathway. Therefore, HA/PEI-RH NYPs have advantages of good gastric stability, β-glucanase-sensitive release ability, macrophage-targeted ability, and anti-UC effects. These advantages indicate YPs-entrapped multifunctional NPs are a promising oral drug delivery system for UC therapy.

Exposure-based ecotoxicity assessment of Co3O4 nanoparticles in marine microalgae.

The exposure-effect study was conducted to evaluate the effect of Co3O4 nanoparticles on Tetraselmis suecica. The growth suppressing effect has been observed during the interaction between nanoparticles and microalgae as indicated by 72 h EC50 (effective concentration of a chemical at which 50% of its effect is observed) value (45.13±3.95 mg/L) of Co3O4 nanoparticles for Tetraselmis suecica. Decline in chlorophyll a content also indicated the compromised photosynthetic ability and physiological state of microalgae. Further biochemical investigation such as increase in extracellular LDH (lactate dehydrogenase) level, ROS (reactive oxygen species), and levels of membrane lipid peroxidation in treated samples signifies the compromised cellular health and membrane disintegration caused by nanoparticles. Parallel to this, the cell entrapment, membrane damage, and attachment of nanoparticles on cell surface were also visualized by SEM-EDX (scanning electron microscope-energy dispersive X-ray) microscopy. The overall results of this study clearly indicated that Co3O4 nanoparticles might have toxic effects on growth of marine microalgae and other aquatic life forms as well. Hence, release of Co3O4 nanoparticles in aquatic ecosystem and resulting ecotoxic effect should be broadly addressed.