Shift In Zeta Potential Research Articles

Dexamethasone-loaded chitosan-decorated PLGA nanoparticles: a step forward in attenuating the COVID-19 cytokine storm?

This study aims to develop and characterize poly (lactic-co-glycolic acid) (PLGA) nanoparticles decorated with chitosan (CS) for the encapsulation of dexamethasone (DEX) (NP-DEX-CS), targeting improved efficacy in the treatment of severe acute respiratory syndrome (SARS) associated with COVID-19. The nanoparticles were systematically characterized for size, zeta potential (ZP), morphology, encapsulation efficiency, and in vitro drug release. Incorporation of CS resulted in significant modifications in the nanoparticles' physical properties, notably an increase in size (from 207.3 ± 6.7nm to 264.4 ± 4.4nm) and a shift in ZP to positive values (from -11.8 ±1.4mV to +30.0 ± 1,6mV). The NP-DEX-CS formulation achieved a high encapsulation efficiency (~79%) and a drug loading capacity of 6.53 ± 0.02%.In addition, the in vitro release rate of DEX from NP-DEX-CS was lower compared to undecorated nanoparticles, with a reduction from approximately 64% to 37% within 24h. Microscopy analyses revealed a smoother surface on the CS-decorated nanoparticles. FTIR and XRD analyses confirmed successful chitosan coating and DEX encapsulation. The CS coating enhanced the tolerability of J774.A1 cells to the nanoparticles, particularly evident at the highest concentration (400ug/mL), resulting in a cell viability ≥70%. Importantly, the NP-DEX-CS significantly reduced levels of nitric oxide and inflammatory cytokines (IL-1, IL-6, IL-12, and TNF-α). These findings suggest that CS-decorated PLGA nanoparticles hold promise as an effective dexamethasone delivery system for treating SARS related to COVID-19.

Improved Therapeutic Efficacy: Liposome-Coated Mesoporous Silica Nanoparticles Delivering Thymoquinone to MCF-7 Cells.

Breast cancer remains a significant global health challenge, with thymoquinone showing promise as a therapeutic agent, but hindered by poor solubility. This study aimed to enhance TQ delivery to MCF-7 breast cancer cells using mesitylene- mesoporous silica nanoparticles coated with liposomes, designed for controlled drug release. Nanoparticles were synthesized using the sol-gel method and coated with phosphatidylserine- cholesterol liposomes. Different nanocharacterization techniques and in vitro assays were employed to assess the drug release kinetics, cellular uptake, cytotoxicity, and apoptosis. The nanoparticles exhibited favorable properties, including a large pore size of 3.6 nm, a surface area of 248.96 m2/g, and a hydrodynamic size of 171.571 ± 8.342 nm with a polydispersity index of 0.182 ± 0.017, indicating uniformity and stability. The successful lipid bilayer coating was confirmed by a zeta potential shift from +6.25 mV to -5.65 mV. The coated nanoparticles demonstrated a slow and sustained drug release profile, with cellular uptake of FITC-formulated nanoparticles being approximately 5-fold higher than free FITC (P < 0.0001). Cytotoxicity assays revealed a significant reduction in cell viability (P < 0.0001), reaching an IC50 value of 25 μM at 48 hours. Apoptosis rates were significantly higher in cells treated with the formulated TQ compared to the free drug and control at both 24 and 48 hours (P < 0.0001). This nanoformulation significantly enhanced TQ delivery, offering a promising strategy for targeted breast cancer therapy. Further preclinical studies are recommended to advance this approach in cancer treatment.

Charge-converting nanocarriers: Phosphorylated polysaccharide coatings for overcoming intestinal barriers

For the design of charge-converting nanocarriers (NCs), cationic lipid-based NCs containing curcumin as model drug were coated with phosphorylated starch (NC-SP) and phosphorylated dextran (NC-DP). NCs showed a drug encapsulation efficiency of 94 % and had a mean size of 175 to 180 nm. The recorded zeta potential of the core NC (cNC) was +8.3 mV, whereas it reversed to −10.6 mV and −7.4 mV after decorating with SP and DP, respectively. Furthermore, a 3-fold higher amount of curcumin having been incorporated in these NCs remained stable within 2 h of UV exposure indicating a photoprotective effect of this delivery system. Charge-converting properties were confirmed by cleavage with intestinal alkaline phosphatase (IAP) and resulted in a zeta potential shift of Δ15.4 mV for NC-SP and Δ11.2 mV for NC-DP. NC-SP and NC-DP showed enhanced mucus permeating properties compared to cNC, that were additionally confirmed by an up to 2.2-fold improved cellular uptake on mucus secreting Caco-2/HT29-MTX cells. According to these results, NC-SP and NC-DP coatings hold promise as a viable and efficient strategy for charge-converting NCs.

Development of a Polymer Ultrasound Contrast Agent Incorporating Nested Carbon Nanodots

Polymer microbubbles have garnered broad interest as potential theranostic agents. However, the capabilities of polymer MBs can be greatly enhanced, particularly regarding the imaging performance and functional versatility of the platform. This study investigates integrating fluorescent carbon nanodots within polylactic acid (PLA) microbubbles. First, the formulations are characterized by their size, microbubble counts, zeta potential, and resonance frequency. Then, the fluorescence capabilities, nanoparticle loading, and acoustic capabilities are examined. Unmodified (U-), carboxylated (C-), and aminated graphene quantum dots (A-GQDs) were separately suspended and synthesized at a 2% w/w ratio with PLA in the organic phase of the water/oil/water double emulsion process. The new microbubbles were characterized using an AccuSizer, Zetasizer, scanning electron microscopy, fluorescence microscopy and fluorimetry, a custom-built acoustic setup, and clinical ultrasound. The GQD microbubbles were sized between 1.4 and 1.9 µm (U = 1.90, C = 1.44, A = 1.72, Unloaded = 2.02 µm). The U-GQD microbubble exhibited a higher bubble concentration/mg PLA ( p &lt; .05) and the A-GQD microbubbles exhibited the greatest shift in zeta potential. Electron microscopy revealed smooth surfaces and a spherical shape, showing that the nanoparticle addition was not deleterious. The A-GQD microbubbles were specifically detectable using DAPI-filtering with fluorescence microscopy and had the highest TRITC-filtered fluorescence. The C-GQD microbubbles had the highest loading efficiency at 59.4% ( p &lt; .05), and the lowest max acoustic enhancement at 5 MHz (U = 19.8, C = 17.6, A = 18.9, Unloaded = 18.5 dB; p &lt; .05). Additionally, all microbubbles were visible and susceptible to inertial cavitation utilizing clinical ultrasound. The A-GQDs showed promise toward improving the theranostic capabilities of the microbubble platform. They have imbued the most advantageous fluorescence capability and slightly improved backscatter enhancement while retaining all the necessary capabilities of an ultrasound contrast agent. Future studies will investigate the coloading potential of A-GQDs and drug within microbubbles.

Enhancing the attraction of positively charged precursors of conductive polymer poly(3,4-ethylenedioxythiophene) by anchoring sulfonate groups in cellulose fibres

Interfacial interactions are key to the development of high-performance coatings such as conductive polymer layers on fibrous materials. In this work, we present an approach of strengthening the interaction by forming ionic bonds between cellulose fibres and the conductive polymer layer by introducing a sulfonate group on cellulose fibres. The ionic bonds are formed between anchored sulfonate group and the positively charged precursor 3,4-ethylenedioxythiophene (EDOT), followed by the deposition and polymerisation of poly(3,4-ethylenedioxythiophene):sulfate (PEDOT:SO4) on the fibrous substrate surface. The conductance of the PEDOT:SO4 coated substrate with anchored sulfonate groups coated may be 1.7 times higher compared to the conductance of the unmodified cellulose substrate depending on experimental conditions. EDX measurements confirm the presence of sulfur and a shift of zeta potential at lower pH supports the evidence of the anionic anchored groups on the fibre surface. Our study therefore provides a new way to enhance the affinity of fibrous cellulose materials towards polymer conductive coatings.

QbD-based optimization and evaluation of chitosan-adorned nanostructured lipid carriers for nose-to-brain delivery of 17β-Estradiol in rat model of Alzheimer's disease

Alzheimer's disease, a prevalent form of dementia affecting millions worldwide, poses a significant challenge, especially in elderly females after postmenopausal. The delivery of 17β-estradiol (EST), a potential therapeutic agent, is hindered by low water solubility and bioavailability. This study aimed to develop, optimize, and characterize nanostructured lipid carriers (NLCs) coated with chitosan (CS) for intranasal administration to enhance EST delivery to the brain for AD management. The NLCs were formulated through a solvent-free melt-emulsification and sonication method and optimized via a Box-Behnken design. The EST-NLCs that were optimized showed favorable colloidal properties. They had a particle size (PS) of 115.64 ± 2.44 nm, a polydispersity index (PDI) of 24 ± 1.66 %, a zeta potential (ZP) of −26.5 ± 0.72 mV, and an entrapment efficiency (EE) of 81.99 ± 1.43 %. When CS was introduced to form CS-EST-NLCs, it led to changes in the PS (126.76 ± 3.04 nm), % PDI (22.7 ± 1.78), a shift in ZP from negative to positive (34.07 ± 1.10 mV), and an increase in % EE of 84.39 ± 1.07. Differential scanning calorimetry and powder X-ray diffraction confirmed the amorphous dispersion of EST in the nanocarriers. Surface characterization confirmed the nanoscale size, spherical shape, and smooth exterior. In vitro drug release studies demonstrated a biphasic release pattern, with a burst followed by sustained release, fitting the Korsmeyer-Peppas model. The stability study results confirmed that formulations are stable for three months under ambient room temperature and refrigerated condition. Ex vivo studies supported the safety of EST using NLCs. Behavioral testing revealed the superior efficacy of intranasally administered CS-EST-NLCs compared to plain EST dispersion. The findings suggest that the biodegradable and mucoadhesive CS-EST-NLCs hold promise as a viable drug carrier for intranasal delivery to the brain, demonstrating both good safety and high tolerability.

Effect of Bulk Nanobubbles on the Flocculation and Filtration Characteristics of Kaolin Using Cationic Polyacrylamide

This study investigated the influence of bulk nanobubbles (NBs) on the flocculation and filtration behavior of kaolin suspensions treated with cationic polyacrylamide (CPAM). Traditionally, flocculation relies on bridging mechanisms by polymers like CPAM. The present work examines the possibility of combining NBs with CPAM to achieve more efficient kaolin separation. The settling behavior of kaolin suspensions with and without bulk nanobubbles was compared. The results with 2 mL CPAM and 300 s settling time revealed that bulk NBs significantly enhanced flocculation efficiency, with supernatant zone height reductions exceeding 50% compared to CPAM alone, indicating a faster settling rate resulting from bulk NBs. This improvement in the settling rate is attributed to NBs’ ability to reduce inter-particle repulsion (as evidenced by a shift in zeta potential from −20 mV to −10 mV) and bridge kaolin particles, complementing the action of CPAM. Additionally, the study demonstrated that bulk NBs improved dewatering characteristics by lowering the medium resistance and specific cake resistance during filtration. These findings pave the way for the utilization of bulk NBs as a novel and efficient strategy for kaolin separation in mineral processing, potentially leading to reduced processing times and lower operational costs.

Phosphatase-degradable nanoparticles providing sustained drug release

AimThe study aimed to develop enzyme-degradable nanoparticles comprising polyphosphates and metal cations providing sustained release of the antibacterial drug ethacridine (ETH). MethodsCalcium polyphosphate (Ca-PP), zinc polyphosphate (Zn-PP) and iron polyphosphate nanoparticles (Fe-PP NPs) were prepared by co-precipitation of sodium polyphosphate with cations and ETH. Developed nanocarriers were characterized regarding particle size, PDI, zeta potential, encapsulation efficiency and drug loading. Toxicological profile of nanocarriers was assessed via hemolysis assay and cell viability on human blood erythrocytes and HEK-293 cells, respectively. The enzymatic degradation of NPs was evaluated in presence of alkaline phosphatase (ALP) monitoring the release of monophosphate, shift in zeta potential and particle size as well as drug release. The antibacterial efficacy against Escherichia coli was determined via microdilution assay. ResultsNPs were obtained in a size range between 300 – 480 nm displaying negative zeta potential values. Encapsulation efficiency was in the range of 83.73 %– 95.99 %. Hemolysis assay underlined sufficient compatibility of NPs with blood cells, whereas drug and NPs showed a concentration dependent effect on HEK-293 cells viability. Ca- and Zn-PP NPs exhibited remarkable changes in zeta potential, particle size, monophosphate and drug release upon incubation with ALP, compared to Fe-PP NPs showing only minor differences. The released ETH from Ca- and Zn-PP nanocarriers retained the antibacterial activity against E. coli, whereas no antibacterial effect was observed with Fe-PP NPs. ConclusionPolyphosphate nanoparticles cross-linked with divalent cations and ETH hold promise for sustained drug delivery triggered by ALP for parental administration.

Glycine betaine modulates extracellular polymeric substances to enhance microbial salinity tolerance

High salinity inhibits microbial activity in the bioremediation of saline wastewater. To alleviate osmotic stress, glycine betaine (GB), an osmoprotectant, is added to enhance the secretion of extracellular polymeric substances (EPS). These EPS are pivotal in withstanding environmental stressors, yet the intricate interplay between GB supplementation and microbial responses through EPS modifications—encompassing composition, molecular architecture, and electrochemical features—remains elusive in hypersaline conditions. Here we show microbial strategies for salinity endurance by investigating the impact of GB on the dynamic alterations of EPS properties. Our findings reveal that GB supplementation at 3.5% salinity elevates the total EPS (T-EPS) content from 12.50 ± 0.05 to 24.58 ± 0.96 mg per g dry cell weight. The observed shift in zeta potential from −28.95 to −6.25 mV at 0% and 3.5% salinity, respectively, with GB treatment, indicates a reduction in electrostatic repulsion and compaction. Notably, the EPS protein secondary structure transition from β-sheet to α-helix, with GB addition, signifies a more compact protein configuration, less susceptible to salinity fluctuations. Electrochemical analyses, including cyclic voltammetry (CV) and differential pulse voltammetry (DPV), reveal GB's role in promoting the release of exogenous electron shuttles, such as flavins and c-type cytochromes (c-Cyts). The enhancement in DPV peak areas (QDPV) with GB addition implies an increase in available extracellular electron transfer sites. This investigation advances our comprehension of microbial adaptation mechanisms to salinity through EPS modifications facilitated by GB in saline habitats.

Overcoming intestinal barriers by heparanase-responsive charge-converting nanocarriers

In this study, we present a novel approach for overcoming intestinal barriers by utilizing heparanase-responsive charge-converting nanocarriers (NCs). These NCs are designed to undergo charge conversion in response to the activity of heparanase (HPSE), an enzyme commonly overexpressed in cancer cells. Nanostructured lipid carriers (NLCs) and solid lipid nanocarriers (SLNs) with a positively charged core were coated with heparin (Hep), resulting in a negative surface charge and a size between 195 and 220 nm. However, upon encountering heparanase, heparin undergoes enzymatic cleavage, resulting in zeta potential shift from –22.1 to +8.3 mV for NLC-Hep and from −19.8 to +5.1 mV for SLN-Hep. Heparin-coated NCs showed more than 6-fold higher mucus permeating properties compared to the uncoated NCs. In vitro experiments using the heparanase-expressing cancer cell line HT29 demonstrated an up to 4-fold improved cellular uptake of the heparin coated NCs compared to co-incubation with the HPSE inhibitor suramin. Furthermore, cellular uptake was investigated on Caco-2 cells and on a Caco-2/HT29-MTX co-culture. Overall, this study highlights the potential of heparanase-responsive charge-converting NCs as a promising strategy for overcoming intestinal barriers and enhancing cellular uptake.

Zeta potential shifting nanoemulsions comprising single and gemini tyrosine-based surfactants

AimThis study aims to design and evaluate zeta potential shifting nanoemulsions comprising single and gemini type tyrosine-based surfactants for specific cleavage by tyrosine phosphatase. MethodsTyrosine-based surfactants, either single 4-(2-amino-3-(dodecylamino)-3-oxopropyl)phenyl dihydrogen phosphate (AF1) or gemini 4-(2-amino-3-((1-(dodecylamino)-3-(4-hydroxyphenyl)-1-oxopropan-2-yl)amino)-3-oxopropyl)phenyl dihydrogen phosphate (AF2) type were synthesized via amide bond formation of tyrosine with dodecylamine followed by phosphorylation. These surfactants were incorporated into nanoemulsions. Nanoemulsions were monitored by incubation with isolated tyrosine phosphatase as well as secreted tyrosine phosphatase of Escherichia coli in terms of phosphate release and zeta potential change. ResultsVia isolated tyrosine phosphatase, and mediated by E. coli, phosphate groups of either single or gemini tyrosine-based surfactants could be cleaved by secreted tyrosine phosphatase. Nanoemulsions comprising a single tyrosine-based surfactant resulted in a charge shift from - 13.46 mV to - 4.41 mV employing isolated tyrosine phosphatase whilst nanoemulsions consisting of a gemini tyrosine-based surfactant showed a shift in zeta potential from - 15.92 mV to - 5.86 mV, respectively. ConclusionNanoemulsions containing tyrosine-based surfactants represent promising zeta potential shifting nanocarrier systems targeting tyrosine phosphatase secreting bacteria.

Phosphatase-degradable nanoparticles: A game-changing approach for the delivery of antifungal proteins

HypothesisPolyphosphate nanoparticles as phosphatase-degradable carriers for Penicillium chrysogenum antifungal protein (PAF) can enhance the antifungal activity of the protein against Candida albicans biofilm. ExperimentsPAF-polyphosphate (PP) nanoparticles (PAF-PP NPs) were obtained through ionic gelation. The resulting NPs were characterized in terms of their particle size, size distribution and zeta potential. Cell viability and hemolysis studies were carried out in vitro on human foreskin fibroblasts (Hs 68 cells) and human erythrocytes, respectively. Enzymatic degradation of NPs was investigated by monitoring release of free monophosphates in the presence of isolated as well as C. albicans-derived phosphatases. In parallel, shift in zeta potential of PAF-PP NPs as a response to phosphatase stimuli was determined. Diffusion of PAF and PAF-PP NPs through C. albicans biofilm matrix was analysed by fluorescence correlation spectroscopy (FCS). Antifungal synergy was evaluated on C. albicans biofilm by determining the colony forming units (CFU). FindingsPAF-PP NPs were obtained with a mean size of 300.9 ± 4.6 nm and a zeta potential of −11.2 ± 2.8 mV. In vitro toxicity assessments revealed that PAF-PP NPs were highly tolerable by Hs 68 cells and human erythrocytes similar to PAF. Within 24 h, 21.9 ± 0.4 μM of monophosphate was released upon incubation of PAF-PP NPs having final PAF concentration of 156 μg/ml with isolated phosphatase (2 U/ml) leading to a shift in zeta potential up to −0.7 ± 0.3 mV. This monophosphate release from PAF-PP NPs was also observed in the presence of C. albicans-derived extracellular phosphatases. The diffusivity of PAF-PP NPs within 48 h old C. albicans biofilm matrix was similar to that of PAF. PAF-PP NPs enhanced antifungal activity of PAF against C. albicans biofilm decreasing the survival of the pathogen up to 7-fold in comparison to naked PAF. In conclusion, phosphatase-degradable PAF-PP NPs hold promise as nanocarriers to augment the antifungal activity of PAF and enable its efficient delivery to C. albicans cells for the potential treatment of Candida infections.

Study on inhibition effect and mechanism of sodium humate in hematite reverse flotation

The inhibitor can improve the hydrophilicity of minerals and prevent minerals from interacting with collectors. It plays an important role in the reverse cation flotation of iron ore, and it has become the focus of current research to find efficient, environmental friendly and cheap inhibitors. Sodium humate (NaHA) is a product extracted from weathered Lignite by means of biodegradation and organic decomposition. In this study, this new inhibitor NaHA was used to separate hematite and quartz. The results of micro-flotation showed that an appropriate concentration of NaHA could selectively inhibit hematite and realize the effective separation of quartz and hematite. Zeta potential and adsorption measurement results showed that after treatment by NaHA, the negative shift of zeta potential of hematite was more obvious, and could prevent the further adsorption of dodecylamine (DDA). The adsorption capacity of NaHA on hematite surface was much greater than that on quartz surface. FTIR results showed that there was chemisorption of NaHA on the surface of hematite but no on the quartz. XPS analysis again confirmed that NaHA may adsorb on the surface of hematite through coordination with surface iron.

Chitosan – Polyphosphate nanoparticles for a targeted drug release at the absorption membrane

The aim of this study was to develop nanoparticles (NPs) providing a targeted drug release directly on the epithelium of the intestinal mucosa.NPs were prepared via ionic gelation between cationic chitosan (Cs) and anionic polyphosphate (PP). The resulting NPs were characterized by their size, polydispersity index (PDI) and zeta potential. Isolated and cell-associated intestinal alkaline phosphatase (IAP) was employed to trigger polyphosphate cleavage in Cs-PP NPs which was quantified via malachite green assay. In parallel, the shift in zeta potential was determined. In-vitro drug release studies were performed in Franz diffusion cells with Cs-PP NPs containing rhodamine 123 as model active ingredient. Furthermore, cytotoxicity of Cs-PP NPs was assessed via resazurin assay on Caco-2 cells as well as via hemolysis assay on red blood cells.Cs-PP NPs exhibited an average size of 144.17 ± 10.95 nm and zeta potential of -12.6 ± 0.50 mV. The encapsulation efficiency of rhodamine 123 by Cs-PP NPs was 86.8%. After incubation with isolated IAP for 3 h the polyphosphate of Cs-PP NPs was cleaved to monophosphate and zeta potential raised up to -2.3 ± 0.30 mV. Cs-PP NPs showed a non-toxic profile. Within 3 h, 62.0 ± 10.8% and 14.1 ± 2.2% of total rhodamine 123 was released from Cs-PP NPs upon incubation with isolated as well as porcine intestine derived intestinal alkaline phosphatase (IAP), respectively.According to these results, Cs-PP NPs are promising drug delivery systems to enable a drug targeted release at the absorption membrane.

Quaternary amine functionalized chitosan for enhanced adsorption of low concentration phosphate to remediate environmental eutrophication

Phosphate contamination of natural waterways from agricultural runoff is a major global issue due to its widespread occurrence and severe environmental effects, namely accelerated eutrophication, and subsequent negative impacts on aquatic ecosystems. This study reports on the synthesis of a biopolymer capable of remediating environmentally relevant concentrations of phosphate: a glutaraldehyde crosslinked chitosan, quaternised with 2-chloro-N,N-diethylethylamine hydrochloride (DEAE). This modification generated a notable increase in the overall positive surface charge on the chitosan promoting adsorption of phosphate anions. The chemical transformations on the adsorbent’s surface are evidenced by the significant shift in zeta potential, increasing from –12 eV to +27 eV at pH 7, and analysis of the XPS spectra showed a substantial increase in the N1s peak centred at 402 eV, corresponding to the positively charged amine species. Langmuir isotherm modelling indicated the maximum capacity for phosphate to be 20.1 mg P/g and a Langmuir constant of 1.15 L/mg. Other adsorption studies were designed to focus on the identified issue of low concentration phosphate removal and demonstrated the modified-chitosan to be a highly effective adsorbent: using an adsorbent dose of 2 g/L resulted in 97% removal, leaving less than 0.1 ppm P in solution. A higher removal, 98.4%, was achieved at a dose of 6 g/L, however this represented considerable diminishing returns. Furthermore, there was no measurable loss of the intrinsic adsorption ability after 9 adsorption-desorption cycles showing exceptionally effective regeneration using 0.1 M NaCl.

Phosphate decorated lipid-based nanocarriers providing a prolonged mucosal residence time

The aim of this study was to develop phosphate decorated lipid-based nanocarriers including self-emulsifying drug delivery systems (SEDDS), solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) to extend their mucosal residence time. All nanocarriers contained tetradecyltrimethylammonium bromide (TTAB) and polyoxyethylene (9) nonylphenol monophosphate ester (PNPP) for surface decoration. Zeta potential, cytotoxicity, charge conversion and phosphate release studies using isolated intestinal alkaline phosphatase (IAP) and Caco-2 cells were performed. Moreover, the residence time of nanocarriers was determined on porcine intestinal mucosa. Results showed a shift from negative to positive zeta potential due to the addition of TTAB and charge conversion back to a negative zeta potential when also PNPP was added. Up to a concentration of 0.3 %, lipid-based nanocarriers were not toxic. Charge conversion studies with IAP revealed the highest zeta potential shift for NLCTTAB-PNPP with almost Δ22 mV. Phosphate release studies using isolated IAP as well as Caco-2 cells showed a fast phosphate release for SEDDSTTAB-PNPP, SLNTTAB-PNPP and NLCTTAB-PNPP. SLN TTAB-PNPP and NLC TTAB-PNPP provided the highest increase in mucosal residence time that was 4-fold more prolonged than that of blank formulations. In conclusion, phosphate modified lipid-based nanocarriers can essentially prolong the intestinal residence time of their payload.

Design of nanostructured lipid carriers and solid lipid nanoparticles for enhanced cellular uptake

In this study PEG-free and zeta potential changing lipid-based nanocarriers providing enhanced cellular uptake were developed. Nanostructured lipid carriers (NLC), consisting of paraffin wax, caprylic/ capric triglyceride, cetyltrimethylammoniumchloride and either soy lecithin or polyglycerol-4 laurate and solid lipid nanoparticles (SLN) with the same composition but without the liquid lipid content were developed. All formulations exposed a positive surface charge and were then coated with the polyphosphate Graham’s salt. Phosphate release from these formulations was evaluated by incubation with intestinal alkaline phosphatase as well as on a Caco-2 monolayer and zeta potentials were measured. Additionally, cellular uptake studies were performed.Within 5 h, a remarkable amount of phosphate was released from all formulations incubated with intestinal alkaline phosphatase. Enzymatically induced phosphate release with intestinal alkaline phosphatase led to a zeta potential shift up to Δ 26 mV. Results of phosphate release and zeta potential change were confirmed on Caco-2 cells. Cellular uptake studies on Caco-2 cells showed an up to 5.6-times higher uptake compared to cells with inhibited phosphatase. According to these results, polyphosphate coating is a powerful tool to obtain lipid-based nanocarriers for enhanced cellular uptake.

A functional corona around extracellular vesicles enhances angiogenesis, skin regeneration and immunomodulation.

Nanoparticles can acquire a plasma protein corona defining their biological identity. Corona functions were previously considered for cell‐derived extracellular vesicles (EVs). Here we demonstrate that nano‐sized EVs from therapy‐grade human placental‐expanded (PLX) stromal cells are surrounded by an imageable and functional protein corona when enriched with permissive technology. Scalable EV separation from cell‐secreted soluble factors via tangential flow‐filtration (TFF) and subtractive tandem mass‐tag (TMT) proteomics revealed significant enrichment of predominantly immunomodulatory and proangiogenic proteins. Western blot, calcein‐based flow cytometry, super‐resolution and electron microscopy verified EV identity. PLX‐EVs partly protected corona proteins from protease digestion. EVs significantly ameliorated human skin regeneration and angiogenesis in vivo, induced differential signalling in immune cells, and dose‐dependently inhibited T cell proliferation in vitro. Corona removal by size‐exclusion or ultracentrifugation abrogated angiogenesis. Re‐establishing an artificial corona by cloaking EVs with fluorescent albumin as a model protein or defined proangiogenic factors was depicted by super‐resolution microscopy, electron microscopy and zeta‐potential shift, and served as a proof‐of‐concept. Understanding EV corona formation will improve rational EV‐inspired nano‐therapy design.

Effect of peracetic acid as a depressant on the flotation separation of chalcopyrite from arsenopyrite

• Separation of arsenopyrite from chalcopyrite hindered by similar floatabilities. • Depression of arsenopyrite flotation required for better separation. • Effect of peracetic acid as a depressant of arsenopyrite was investigated in this study. • Found to greatly aid in flotation separation under neutral pH conditions. Arsenopyrite is an arsenic-bearing mineral that frequently occurs with chalcopyrite in polymetallic sulphide deposits. Their separation via existing methods and reagents involved in the flotation process, however, remains sub-par due to difficulties in the effective depression of arsenopyrite. In this study, the eco-friendly organic oxidant of peracetic acid (PAA, CH 3 C( O)OOH) was used for the first time ever to effectively depress arsenopyrite under conditions of neutral pH. Flotation experiments, adsorption tests, zeta potential analysis, X-ray photoelectron spectroscopy (XPS), and time-of-flight secondary ion mass spectroscopy (ToF-SIMS) were performed to investigate the depression mechanism of PAA on arsenopyrite. Single mineral flotation results showed PAA to have a massive depressive effect on arsenopyrite, reducing its froth recovery from 90% to 3% but only marginally affecting the froth recovery of chalcopyrite. Mixed minerals and bench-scale flotation tests further verified that PAA was an efficient arsenopyrite depressant. Adsorption test results, meanwhile, indicated that PAA could significantly reduce the adsorption of xanthate on the surface of arsenopyrite, but not on that of chalcopyrite. Zeta potential measurements, on the other hand, suggested a strong interaction between the surface of arsenopyrite and PAA compared with chalcopyrite, which induced a positive shift of zeta potential on the arsenopyrite surface. XPS analysis demonstrated that PAA only slightly oxidizes the surface of chalcopyrite, and a very small amount of iron oxide, sulfur oxide and copper oxide were generated, indicating that the surface was still hydrophobic. On the contrary, PAA could strongly oxidize the surface of arsenopyrite and generate a large number of oxygen-containing species, such as As(III)–O, As(V) − O, Fe(III) − O, Fe(III)–SO, SO 3 2− , and SO 4 2− . This was supported by measuring the contents of these oxides of iron, sulphur, and arsenic on the surface of arsenopyrite, which were found to increase from 47.13% to 88.56%, 14.95% to 45.49%, and 45.94% to 81.57%, respectively. Finally, hydrophilic oxide films containing AsO 2 − , AsO 3 − , SO 3 2− , Fe(OH) 3 , FeAsO 4 , and Fe 2 (SO 4 ) 3 were formed on the arsenopyrite surface, which further contributed to its depression.

Dual-Acting Zeta-Potential-Changing Micelles for Optimal Mucus Diffusion and Enhanced Cellular Uptake after Oral Delivery.

Context: Overcoming the intestinal mucosal barrier can be a challenge in drug delivery. Nanoemulsions with negative zeta potentials can effectively permeate the mucus layer, but those with positive zeta potentials are better taken up by cells; a nanoemulsion with capricious zeta potential from negative to positive can achieve both good permeation and high uptake. Objective: This study aimed to develop dual-acting zeta-potential-amphoteric micelles enabling optimal muco-permeation and enhancement of cellular uptake. Methods: A micellar pre-concentrate was prepared from 15% Labrasol, 15% Kolliphor EL, 30% Kolliphor RH 40, and 40% dimethylsulfoxide. The micellar pre-concentrate was loaded with anionic stearic acid (SA), forming ionic complexes with cationic polymers at a ratio of 25:1 with Eudragit RS 100 and Eudragit RL 100. Blank micelles and those containing complexes were separately diluted in physiological buffers and examined for their droplet sizes, polydispersity indices (PDIs), zeta potentials, and cytotoxicity. The SA release from the micellar complexes was evaluated in 0.1 mM phosphate buffer (pH 6.8) containing 0.001% fluorescein, thereby enabling an instant decrease in fluorescence. Finally, the micelles were loaded with the model drug fluorescein diacetate (FDA) and evaluated for their muco-permeation behavior and cellular uptake. Results: The micellar dilutions formed micelles at the critical micelle concentration (CMC) of 312 µg/mL and showed a uniform average droplet size of 14.2 nm, with a PDI < 0.1. Micellar dilutions were non-cytotoxic when used at 1:100 in a physiological medium. Micelles loaded with ionic complexes achieved a sustained release of 95.5 ± 3.7% of the SA in 180 min. Moreover, the zeta potential of the complex-loaded micelles shifted from −5.4 to +1.8 mV, whereas the blank micelles showed a stabilized zeta potential of −10 mV. Furthermore, the negatively charged blank and complex-loaded micelles exhibited comparable muco-permeation, with an overall average of 58.2 ± 3.7% diffusion of FDA. The complex-loaded micellar droplets, however, provided a significantly higher cellular uptake of the model drug FDA (2.2-fold, p ≤ 0.01) Conclusion: Due to undergoing a shift in zeta potential, the modified micelles significantly enhanced cellular uptake while preserving mucus-permeating properties.