Neutral Surface Charge Research Articles

Toward fabrication of fouling resistant pervaporation membrane for desalination: Surface modification of TFC membrane via grafting of mPEG-NH2

A highly hydrophilic and fouling resistant membrane was developed via surface modification of a thin film composite membrane (TFC), prepared from polyacrylonitrile/polyvinyl alcohol (PAN/PVA), by polydopamine (PDA) coating and methoxy polyethylene glycol amine (mPEG-NH2) grafting (TFC/PDA-g-PEG). Various analyses were done on the membranes to investigate the quality and effectiveness of the modification. Based on the results, the pristine TFC membrane was positively charged (+7.71 mV), while the PDA coated TFC membrane (TFC/PDA) showed negative zeta potential (−1.65 mV), and TFC/PDA-g-PEG membrane had almost neutral surface charge (+0.15 mV). The water contact angle of the TFC membrane reduced from 74.1° to 46.2° after PDA coating. By grafting of mPEG-NH2 on TFC/PDA membrane, a further decrease in the water contact angle of the membrane was obtained (27.6°). The permeation flux of 75.7 kg/(m2.h) and salt rejection of 99.91 % were attained by TFC/PDA-g-PEG membrane in the treatment of 35 g/L salt solution at 65 °C. The antifouling behavior of virgin and modified TFC membranes against the foulant solution revealed that TFC/PDA-g-PEG membrane had an excellent resistance against fouling agents compared to TFC/PDA and unmodified membranes.

Net-Neutral Nanoparticles-Extruded Microcapsules for Oral Delivery of Insulin.

Oral delivery of insulin could widely improve the quality of life of diabetic patients but still requires further exploration. Commonly utilized oral delivery vehicles hardly penetrate the intestinal mucus barrier, thus greatly hurdling their therapeutic efficacy. State-of-the-art technology shows that coating particles with neutral surface charge could reduce adsorption of mucins and improved the transport of particles within mucus. However, the synthesis of net-neutral particles (NNs) usually need complex purification and processing procedure. Herein, the NNs were conveniently constructed by simply adjusting the ratio of positive (chitosan) and negative (γ-glutamic acid) materials. To further achieve the optimal bioavailability of NNs, NNs formed materials were package in to wild chrysanthemum pollens, obtaining pH-triggered nanoparticles-extruding microcapsules (PNMs@insulin). At the small intestine pH value (∼6.0), the amino groups of CS deprotonate gradually and trigger the swelling, followed by the rapid extrusion of NNs through nano-orifices on the pollens' surface. After oral administration of the microcapsules, plasma insulin levels were enhanced significantly with a high oral bioavailability of >40%, leading to a remarkable and longer-sustained blood glucose-reducing effect. Moreover, we discovered that the empty pollen shells could act as a potential saccharide-adsorbing agent, which helps to manage sugar intake. This oral strategy of insulin will provide a vast potential for daily and facile diabetes treatment.

Poly lactic‐co‐glycolic acid‐alginate nanocarrier for efficient drug delivery to liver cancer cells

AbstractEfficient drug delivery systems (DDSs) can potentially replace with conventional modalities in cancer therapy, like liver cancer. In this study, a novel folic acid (FA)‐functionalised and alginate (Alg)‐modified poly lactic‐co‐glycolic acid (PLGA) nanocomposite was developed for delivery of doxorubicin (Dox) to HepG2 and Huh7 liver cancer cells. After synthesising the nanocarrier, several analytical devices, including FT‐IR, DLS, TGA, and TEM, were employed for its characterisation. Nano‐metric size (55 and 85 nm in diameter), close to neutral surface charge, semi‐spherical morphology, and successful synthesis were approved. Dox entrapment efficiency was determined near 1%, and sustained and pH‐sensitive drug release behaviours of nanocarrier were ascertained for DDS. Afterwards, the cell viability test was carried out to study the HepG2 and Huh7 cells suppression capability of FA‐PLGA‐Dox‐Alg. About 12% and 10% cell viabilities were observed in HepG2 and Huh7 cancer cells after 24 h treatment with 400 nM concentration of FA‐PLGA‐Dox‐Alg nanocarrier respectively. The IC50 value was observed for 100 nM after 24 h of treatment in cancer cells. These data have indicated that fabricated nanocarrier could be promising DDS against liver cancer and replace with conventional approaches in cancer treatment, like chemotherapy.

Formulation of benznidazole-lipid nanocapsules: Drug release, permeability, biocompatibility, and stability studies

Benznidazole, a poorly soluble in water drug, is the first-line medication for the treatment of Chagas disease, but long treatment periods at high dosages cause several adverse effects with insufficient activity in the chronic phase. According to these facts, there is a serious need for novel benznidazole formulations for improving the chemotherapy of Chagas disease. Thus, this work aimed to incorporate benznidazole into lipid nanocapsules for improving its solubility, dissolution rate in different media, and permeability. Lipid nanocapsules were prepared by the phase inversion technique and were fully characterized. Three formulations were obtained with a diameter of 30, 50, and 100 nm and monomodal size distribution with a low polydispersity index and almost neutral zeta potential. Drug encapsulation efficiency was between 83 and 92 % and the drug loading was between 0.66 and 1.04 %. Loaded formulations were stable under storage for one year at 4 °C. Lipid nanocapsules were found to protect benznidazole in simulated gastric fluid and provide a sustained release platform for the drug in a simulated intestinal fluid containing pancreatic enzymes. The small size and the almost neutral surface charge of these lipid nanocarriers improved their penetration through mucus and such formulations showed a reduced chemical interaction with gastric mucin glycoproteins. LNCs. The incorporation of benznidazole in lipid nanocapsules improved the drug permeability across intestinal epithelium by 10-fold compared with the non-encapsulated drug while the exposure of the cell monolayers to these nanoformulations did not affect the integrity of the epithelium.

Synthesis of Chitosan Oligosaccharide-Loaded Glycyrrhetinic Acid Functionalized Mesoporous Silica Nanoparticles and In Vitro Verification of the Treatment of APAP-Induced Liver Injury.

the study was to find a suitable treatment for acute drug-induced liver injury. The use of nanocarriers can improve the therapeutic effect of natural drugs by targeting hepatocytes and higher loads. firstly, uniformly dispersed three-dimensional dendritic mesoporous silica nanospheres (MSNs) were synthesized. Glycyrrhetinic acid (GA) was covalently modified on MSN surfaces through amide bond and then loaded with COSM to form drug-loaded nanoparticles (COSM@MSN-NH2-GA). The constructed drug-loaded nano-delivery system was determined by characterization analysis. Finally, the effect of nano-drug particles on cell viability was evaluated and the cell uptake in vitro was observed. GA was successfully modified to obtain the spherical nano-carrier MSN-NH2-GA (≤200 nm). The neutral surface charge improves its biocompatibility. MSN-NH2-GA has high drug loading (28.36% ± 1.00) because of its suitable specific surface area and pore volume. In vitro cell experiments showed that COSM@MSN-NH2-GA significantly enhanced the uptake of liver cells (LO2) and decreased the AST and ALT indexes. this study demonstrated for the first time that formulation and delivery schemes using natural drug COSM and nanocarrier MSN have a protective effect on APAP-induced hepatocyte injury. This result provides a potential nano-delivery scheme for the targeted therapy of acute drug-induced liver injury.

Encapsulation of morin in lipid core/PLGA shell nanoparticles significantly enhances its anti-inflammatory activity and oral bioavailability

Morin (3,5,7,2′,4′-pentahydroxyflavone; MR) is a bioactive plant polyphenol whose therapeutic efficacy is hindered by its poor biopharmaceutical properties. The purpose of this study was to develop a nanoparticle (NP) formulation to enhance the bioactivity and oral bioavailability of MR. The nanoprecipitation techniquewas employed to encapsulate MR in lipid-cored poly(lactide-co-glycolide) (PLGA) NPs. The optimal NPs were about 200 nm in size with an almost neutral surface charge and a loading efficiency of 82%. The NPs exhibited sustained release of MR within 24 h. In vitro antioxidant assays showed that MR encapsulation did not affect its antioxidant activity. On the other hand, anti-inflammatory assays in lipopolysaccharide-stimulated macrophages revealed a superior anti-inflammatory activity of MR NPs compared to free MR. Furthermore, oral administration of MR NPs to mice at a single dose of 20 mg/kg MR achieved a 5.6-fold enhancement in bioavailability and a prolongation of plasma half-life from 0.13 to 0.98 h. The results of this study present a promising NP formulation for MR which can enhance its oral bioavailability and bioactivity for the treatment of different diseases such as inflammation.

Thermosensitive Copolymeric PLGA-PEG-PLGA Nanomicelles of Raloxifene: Synthesis, Formulation, and In-vitro Characterization

The objective of the present research study has been to synthesize (PLGA-PEG-PLGA), a thermolabile and biodegradable triblock copolymer. The polymer was subjected to differential evaluation using NMR, XRD, and FTIR techniques for characterization. Raloxifene, a potential therapeutic for breast cancer, exerts poor water solubility and a low fraction of bioavailability owing to its pharmacokinetic properties. The synthesized polymer was used to load raloxifene-encapsulating polymeric micelles, which were then subjected to several evaluations with the aim of improving solubility and bioavailability standards. Zeta potential for the developed formulation was approximately -0.73 mV, indicating a relatively neutral surface charge. It subsequently emerged that the sizes of the blank and raloxifene-loaded micelles were 40.18 and 42.18 nm, respectively. The drug encapsulating capacity and% drug loading capacity were determined to be 73.4 ± 0.34% and drug loading 6.04 ± 0.002% (w/w), respectively. In-vitro study illustrated a 94.37% sustained release drug profile for 120 hours. In this research study, polymeric raloxifene nanomicelles were successfully prepared to enhance solubility, bioavailability, and antitumor effect due to the smaller size of the micelles.

Caffeic acid loaded into engineered lipid nanoparticles for Alzheimer's disease therapy

Alzheimer's disease (AD) is an incurable neurological illness and the leading cause of dementia, characterized by amyloid β (Aβ) fibril deposits. Caffeic acid (CA) has demonstrated potential value for AD therapy due to its anti-amyloidogenic, anti-inflammatory, and antioxidant properties. However, its chemical instability and limited bioavailability limit its therapeutic potential in vivo. Herein, liposomes loading CA were produced by distinct techniques. Taking advantage of the overexpression of transferrin (Tf) receptors in brain endothelial cells, Tf was conjugated to the liposomes’ surface to direct the CA-loaded nanoparticles (NPs) to the blood-brain barrier (BBB). The optimized Tf-modified NPs exhibited a mean size of around 140 nm, a polydispersity index lower than 0.2, and a neutral surface charge, being appropriate for drug delivery. The Tf-functionalized liposomes showed suitable encapsulation efficiency and physical stability for at least 2 months. Furthermore, in simulated physiological settings, the NPs ensured the sustained release of CA for 8 days. The anti-amyloidogenic efficacy of the optimized drug delivery system (DDS) was investigated. The data show that CA-loaded Tf-functionalized liposomes are capable of preventing Aβ aggregation and fibril formation, and disaggregating mature fibrils. Hence, the proposed brain-targeted DDS may be a potential strategy for preventing and treating AD. Future studies in animal models of AD will be valuable to validate the therapeutic efficacy of the optimized nanosystem.

Single-Step Surface Hydrophilization on Ultrafiltration Membrane with Enhanced Antifouling Property for Pome Wastewater Treatment

High organic materials in palm oil mill effluent (POME) can result in serious water pollution. To date, biological treatment has been used to reduce the environmental risks of these effluents prior of their discharge into water streams. However, the effluents’ dark brownish colour remains as a significant issue that must be addressed, as it affects the overall quality of water. Although membrane technology has been frequently used to address these difficulties, membrane fouling has become a serious limitation in POME treatment. On the other hand, zwitterions with balanced charge groups have received growing interest in the fabrication of antifouling membranes due to their hydrated nature. The development of a simple and efficient covalent bonding technique to improve the stability of zwitterions on membrane surfaces remains a challenge. By grafting and co-depositing polyethylenimine (PEI)-based zwitterion (Z-PEI) with super hydrophilic polydopamine (PDA) on the surface of a commercial polysulfone (PSf) ultrafiltration membrane at ambient temperature, a new zwitterionic surface with a neutral surface charge was created (PDA/Z-PEI). This study aims to investigate the effect of different loading ratios of PDA/Z-PEI (1:1, 1:2, and 1:3) and evaluate their performance on treating brownish coloured anaerobically treated POME (AT-POME). SEM and FTIR analysis showed the successful incorporation of the PDA/Z-PEI membrane while the zwitterionic feature is indicated by zeta potential analysis. Water flux analysis demonstrated that a lower water flux was achieved for M-ZPEI membranes as compared to the PSf and PSf-MDPA membranes, attributed by the tight skin layer of PDA-ZPEI. In the development of a tight hydration layer on the membrane surface by zwitterions, zwitterionic membranes demonstrated excellent antifouling capabilities, particularly PDA/Z-PEI with a loading ratio of (1:2) with a flux recovery ratio of around 84% and colour rejection of 81.75%. Overall, this research contributes to the development of a unique coating with improved stability and antifouling properties by altering the membrane surface in a simple and reliable manner.

Nanoparticles of VAV1 siRNA combined with LL37 peptide for the treatment of pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is among the leading causes of cancer-related death, and it is highly resistant to therapy owing to its unique extracellular matrix. VAV1 protein, overexpressed in several cancer diseases including pancreatic cancer (PC), increases tumor proliferation and enhances metastases formation, which are associated with decreased survival. We hypothesized that an additive anti-tumor effect could be obtained by co-encapsulating in PLGA nanoparticles (NPs), the negatively charged siRNA against VAV1 (siVAV1) with the positively charged anti-tumor LL37 peptide, as a counter-ion. Several types of NPs were formulated and were characterized for their physicochemical properties, cellular internalization, and bioactivity in vitro. NPs' biodistribution, toxicity, and bioactivity were examined in a mice PDAC model. An optimal siVAV1 formulation (siVAV1-LL37 NPs) was characterized with desirable physicochemical properties in terms of nano-size, low polydispersity index (PDI), neutral surface charge, high siVAV1 encapsulation efficiency, spherical shape, and long-term shelf-life stability. Cell assays demonstrated rapid engulfment by PC cells, a specific and significant dose-dependent proliferation inhibition, as well as knockdown of VAV1 mRNA levels and migration inhibition in VAV1+ cells. Treatment with siVAV1-LL37 NPs in the mice PDAC model revealed marked accumulation of NPs in the liver and in the tumor, resulting in an increased survival rate following suppression of tumor growth and metastases, mediated via the knockdown of both VAV1 mRNA and protein levels. This proof-of-concept study validates our hypothesis of an additive effect in the treatment of PC facilitated by co-encapsulating siVAV1 in NPs with LL37 serving a dual role as a counter ion as well as an anti-tumor agent.

Cellular Uptake of Modified Mesoporous Bioactive Glass Nanoparticles for Effective Intracellular Delivery of Therapeutic Agents.

There has recently been a surge of interest in mesoporous bioactive glass nanoparticles (MBGNs) as multi-functional nanocarriers for application in bone-reconstructive and -regenerative surgery. Their excellent control over their structural and physicochemical properties renders these nanoparticles suitable for the intracellular delivery of therapeutic agents to combat degenerative bone diseases, such as bone infection, or bone cancer. Generally, the therapeutic efficacy of nanocarriers strongly depends on the efficacy of their cellular uptake, which is determined by numerous factors including cellular features and the physicochemical characteristics of nanocarriers, particularly surface charge. In this study, we have systematically investigated the effect of the surface charge of MBGNs doped with copper as a model therapeutic agent on cellular uptake by both macrophages and pre-osteoblast cells involved in bone healing and bone infections to guide the future design of MBGN-based nanocarriers. Cu-MBGNs with negative, neutral, and positive surface charges were synthesized and their cellular uptake efficiency was assessed. Additionally, the intracellular fate of internalized nanoparticles along with their ability to deliver therapeutic cargo was studied in detail. The results showed that both cell types internalized Cu-MBGNs regardless of their surface charge, indicating that cellular uptake of nanoparticles is a complex process influenced by multiple factors. This similarity in cellular uptake was attributed to the formation of a protein corona surrounding the nanoparticles when exposed to protein-rich biological media, which masks the original nanoparticle surface. Once internalized, the nanoparticles were found to mainly colocalize with lysosomes, exposing them to a more compartmentalized and acidic environment. Furthermore, we verified that Cu-MBGNs released their ionic components (Si, Ca, and Cu ions) in both acidic and neutral environments, leading to the delivery of these therapeutic cargos intracellularly. The effective internalization of Cu-MBGNs and their ability to deliver cargos intracellularly highlight their potential as intracellular delivery nanocarriers for bone-regenerative and -healing applications.

Nanoparticle surface stabilizing agents influence antibacterial action.

The antibacterial properties of nanoparticles are of particular interest because of their potential to serve as an alternative therapy to combat antimicrobial resistance. Metal nanoparticles such as silver and copper nanoparticles have been investigated for their antibacterial properties. Silver and copper nanoparticles were synthesized with the surface stabilizing agents cetyltrimethylammonium bromide (CTAB, to confer a positive surface charge) and polyvinyl pyrrolidone (PVP, to confer a neutral surface charge). Minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and viable plate count assays were used to determine effective doses of silver and copper nanoparticles treatment against Escherichia coli, Staphylococcus aureus and Sphingobacterium multivorum. Results show that CTAB stabilized silver and copper nanoparticles were more effective antibacterial agents than PVP stabilized metal nanoparticles, with MIC values in a range of 0.003 μM to 0.25 μM for CTAB stabilized metal nanoparticles and 0.25 μM to 2 μM for PVP stabilized metal nanoparticles. The recorded MIC and MBC values of the surface stabilized metal nanoparticles show that they can serve as effective antibacterial agents at low doses.

High-performance polyethyleneimine based reverse osmosis membrane fabricated via spin-coating technology

Conventional thin-film composite (TFC) reverse osmosis (RO) membranes prepared by ultrafast and uncontrolled interfacial polymerization (IP) generally have unsatisfactory permeability and high fouling propensity, which distinctly impedes their development and wide application. Controllable thickness and roughness offer an opportunity to optimize the permeability and fouling resistance of RO membranes. In this work, we propose spin-coating assisted multilayer interfacial polymerization (SMIP) as a promising approach to fabricating high-performance RO membranes using polyethyleneimine (PEI) and 1, 3, 5-benzoyl chloride (TMC). SMIP integrates the high efficiency and uniformity of spin-coating technology, the nano-level and individual properties control of multilayer interfacial polymerization, and the simplicity of the IP process. Combining the strong hydrophilicity with low diffusion efficiency and positive charge of PEI, a thin, intrinsically hydrophilic, smoother and almost electro-neutral polyamide (PA) nanofilm was obtained. The optimal RO membrane with a controlled thickness of the selective layer (≈61 nm) has a water permeance of 3.12 L m−2 h−1 bar−1 and an acceptable NaCl rejection of 97.5%, while the strong hydrophilicity, minimal surface roughness and almost neutral surface charge afford it excellent fouling resistance. SMIP technology not only provides a new approach to preparing highly permeable and low-fouling RO membranes using macromolecular monomers, but also has great application potential in other separation membranes due to its precise control of the selective layer.

Examining the Effect of Polymer Extension on Protein-Polymer Interactions That Occur during Formulation of Protein-Loaded Poly(lactic acid-co-glycolic acid)-polyethylene Glycol Nanoparticles.

Protein therapeutics have the potential to treat a wide range of ailments due to the high specificity in their function and their ability to replace missing or mutated genes that encode for key cellular processes. Despite these advantages, protein drugs alone can cause adverse effects, such as the development of cross-reactive neutralizing antibodies. Through the encapsulation of proteins into nanoparticles, adverse effects and protein degradation can be minimized, thus improving protein delivery to sites of interest in the body. Nanoparticles comprised of poly(lactic acid-co-glycolic acid)-polyethylene glycol (PLGA-PEG) diblock copolymer are promising protein delivery systems as they are well characterized, non-toxic, and biocompatible. Desirable nanoparticle characteristics, such as neutral surface charge and uniformity in size and dispersity, can be achieved but often require the iterative manipulation of formulation parameters. Chain conformations in the formulation process are very important, and determining whether or not an extended or semi-collapsed polymer chain in the presence of a protein results in more favorable binding has yet to be investigated experimentally. Therefore, this work used atomistic molecular dynamics to examine the role of polymer extension on protein binding and its impact on the encapsulation process within PLGA-PEG nanoparticles. Three polymers (PLGA-PEG, PLGA, and PEG) were evaluated and iduronate-2-sulphatase (ID2S) was used as a model protein. We found highly expanded PLGA-PEG conformations led to more favorable binding with ID2S. Furthermore, PEG oligomers were observed to undergo transient binding with ID2S that was generally less favorable when compared to the other polymer types. The results also suggest that the relaxation times of the PLGA homopolymer and the PLGA-PEG copolymer at different molecular weights in relevant solvent mediums should be considered.

Adsorption of rhodamine 6G and choline on gold electrodes: a molecular dynamics study

The adsorption of analyte molecules on nano-optoelectrodes (e.g. a combined nanoantenna and nanoelectrode device) significantly affects the signal characteristics in surface-enhanced Raman scattering (SERS) measurements. Understanding how different molecules adsorb on electrodes and their electrical potential modulation helps interpret SERS measurements better. We use molecular dynamics simulations to investigate the adsorption of prototypical analyte molecules (rhodamine 6G and choline) on gold electrodes with negative, neutral, and positive surface charges. We show that both molecules can readily adsorb on gold surfaces at all surface charge densities studied. Nevertheless, the configurations of the adsorbed molecules can differ for different surface charge densities, and adsorption can also change a molecule’s conformation. Rhodamine 6G molecules adsorb more strongly than choline molecules, and the adsorption of both molecules is affected by electrode charge in 0.25 M NaCl solutions. The mechanisms of these observations are elucidated, and their implications for voltage-modulated SERS measurements are discussed.

Spermidine/Spermine N1-Acetyltransferase 1 (SAT1)-A Potential Gene Target for Selective Sensitization of Glioblastoma Cells Using an Ionizable Lipid Nanoparticle to Deliver siRNA.

Spermidine/spermine N1-acetyltransferase 1 (SAT1) responsible for cell polyamine catabolism is overexpressed in glioblastoma multiforme (GB). Its role in tumor survival and promoting resistance towards radiation therapy has made it an interesting target for therapy. In this study, we prepared a lipid nanoparticle-based siRNA delivery system (LNP-siSAT1) to selectively knockdown (KD) SAT1 enzyme in a human glioblastoma cell line. The LNP-siSAT1 containing ionizable DODAP lipid was prepared following a microfluidics mixing method and the resulting nanoparticles had a hydrodynamic size of around 80 nm and a neutral surface charge. The LNP-siSAT1 effectively knocked down the SAT1 expression in U251, LN229, and 42MGBA GB cells, and other brain-relevant endothelial (hCMEC/D3), astrocyte (HA) and macrophage (ANA-1) cells at the mRNA and protein levels. SAT1 KD in U251 cells resulted in a 40% loss in cell viability. Furthermore, SAT1 KD in U251, LN229 and 42MGBA cells sensitized them towards radiation and chemotherapy treatments. In contrast, despite similar SAT1 KD in other brain-relevant cells no significant effect on cytotoxic response, either alone or in combination, was observed. A major roadblock for brain therapeutics is their ability to cross the highly restrictive blood-brain barrier (BBB) presented by the brain microcapillary endothelial cells. Here, we used the BBB circumventing approach to enhance the delivery of LNP-siSAT1 across a BBB cell culture model. A cadherin binding peptide (ADTC5) was used to transiently open the BBB tight junctions to promote paracellular diffusion of LNP-siSAT1. These results suggest LNP-siSAT1 may provide a safe and effective method for reducing SAT1 and sensitizing GB cells to radiation and chemotherapeutic agents.

Impact of water characteristics on UV disinfection of unfiltered water

Abstract The objective of this study was to examine the impact of unfiltered water conditions on UV disinfection. UV biodosimetry tests were conducted over a year using water samples from two treatment plants that apply UV without filtration. The influence of turbidity, absorbance, and zeta potential on UV dose–response curves was analyzed to evaluate relationships between unfiltered water quality and log-inactivation of surrogate organisms. It was observed that diminishing inactivation with increasing UV dose (tailing effect) was governed principally by the surface charge of particulate matter. The increased tailing level observed in raw waters was postulated to be due to having more neutral surface charges, resulting in elevated electrostatic attraction between particles and microorganisms that increased UV resistance. Inactivation at a dose of 35 mJ/cm2 in water samples with low turbidity levels (0.38 NTU) and relatively negative surface charge resulted in 3.0 log-removal in comparison with 2.2 and 2.0 log-removal for samples with turbidity levels of 1.57 and 0.61 NTU, respectively. The results of this study highlight the risks of UV disinfection of unfiltered supplies with respect to the effects of water quality characteristics on UV effectiveness and could be employed to optimize the estimation of UV disinfection potential.

Gelatin Nanoparticles for Complexation and Enhanced Cellular Delivery of mRNA.

Messenger RNA (mRNA) is increasingly gaining interest as a modality in vaccination and protein replacement therapy. In regenerative medicine, the mRNA-mediated expression of growth factors has shown promising results. In contrast to protein delivery, successful mRNA delivery requires a vector to induce cellular uptake and subsequent endosomal escape to reach its end destination, the ribosome. Current non-viral vectors such as lipid- or polymer-based nanoparticles have been successfully used to express mRNA-encoded proteins. However, to advance the use of mRNA in regenerative medicine, it is required to assess the compatibility of mRNA with biomaterials that are typically applied in this field. Herein, we investigated the complexation, cellular uptake and maintenance of the integrity of mRNA complexed with gelatin nanoparticles (GNPs). To this end, GNPs with positive, neutral or negative surface charge were synthesized to assess their ability to bind and transport mRNA into cells. Positively charged GNPs exhibited the highest binding affinity and transported substantial amounts of mRNA into pre-osteoblastic cells, as assessed by confocal microscopy using fluorescently labeled mRNA. Furthermore, the GNP-bound mRNA remained stable. However, no expression of mRNA-encoded protein was detected, which is likely related to insufficient endosomal escape and/or mRNA release from the GNPs. Our results indicate that gelatin-based nanomaterials interact with mRNA in a charge-dependent manner and also mediate cellular uptake. These results create the basis for the incorporation of further functionality to yield endosomal release.

Vitamin E TPGS-Poloxamer Nanoparticles Entrapping a Novel PI3Kα Inhibitor Potentiate Its Activity against Breast Cancer Cell Lines.

N-(2-fluorphenyl)-6-chloro-4-hydroxy-2-quinolone-3-carboxamide (R19) is a newly synthesized phosphatidylinositol 3-kinase alpha (PI3Kα) inhibitor with promising activity against cancer cells. The purpose of this study was to develop a polymeric nanoparticle (NP) formulation for R19 to address its poor aqueous solubility and to facilitate its future administration in preclinical and clinical settings. NPs were prepared by nanoprecipitation using two polymers: D-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS) and the poloxamer Pluronic P123 in different ratios. Physicochemical characterization of the NPs revealed them to be around 100 nm in size with high monodispersity, a spherical morphology, and an almost neutral surface charge. The NPs achieved ~60% drug loading efficiency and sustained release of R19 for up to 96 h, with excellent colloidal stability in serum-containing cell culture media. NPs containing TPGS enhanced R19’s potency against MCF-7 and MDA-MB-231 breast cancer cells in vitro, with half-maximal inhibitory concentrations (IC50) ranging between 1.8 and 4.3 µM compared to free R19, which had an IC50 of 14.7–17.0 µM. The NPs also demonstrated low cytotoxicity against human dermal fibroblasts and more significant induction of apoptosis compared to the free drug, which was correlated with their cellular uptake efficiency. Our findings present a biocompatible NP formulation for the delivery of a cancer-targeted PI3Kα inhibitor, R19, which can further enhance its potency for the treatment of breast cancer and potentially other cancer types.

Self‐assembled nanoprodrugs from reducible dextran‐diethyldithiocarbamate conjugates for robust tumor‐targeted chemotherapy

AbstractThe development of anticancer prodrugs from repurposing approved drugs offers a rich source of potential new medicines for clinical cancer therapy. Herein, a folate‐decorated dextran prodrug (FADP) conjugate based on disulfiram (DSF), a repurposing drug, was designed for tumor‐targeted chemotherapy. The FADP conjugates with a high drug content (>10%) were readily achieved by the disulfide conjugation between orthopyridyl disulfide dextran (5, 10, and 20 kDa) and diethyldithiocarbamate (DDTC) as the metabolite of DSF. Data showed that the FADP conjugates could self‐assemble to form nanosized prodrugs (nanoprodrugs) with neutral surface charge under physiological conditions and that the nanoprodrugs could actively release DDTC in an intracellular reductive environment. In vitro experiments indicated that the FADP conjugates had a low cytotoxicity in CT‐26 cells but yielded marked cytotoxicity in the presence of copper (II) ions. Moreover, the FADP with 10 kDa of dextran (FADP10k) exerted the best anticancer ability in the cells with comparable anticancer efficacy to that of DSF. The significant anticancer ability of the FADP10k was associated with their folate receptor‐mediated uptake in the cells, following by a high cellular uptake level in comparison with the parent dextran prodrug (DP) without folates. The chemotherapy of the CT‐26 tumor xenografted in Balb/c mouse model elicited that the FADP10k group exerted marked tumor growth inhibition with a minor systemic toxicity at DDTC dose of 20 mg Kg−1 and the anticancer efficacy was superior to that obtained by the DP and DSF groups. This work highlights a high potential of DSF‐based dextran prodrugs for cancer chemotherapy.