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1.
Environ Pollut ; 292(Pt A): 118277, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34610413

RESUMO

In this study, we firstly used alginate to enhance an electrokinetic technology to remediate soil contaminated with divalent heavy metals (Pb2+, Cu2+, Zn2+). The mechanisms of alginate-associated migration of metal ions in electric field were confirmed. Alginate resulted in a high electrical current during electrokinetic process, and soil conductivity also increased after remediation. Obvious changes in both electroosmotic flow and soil pH were observed. Moreover, these factors were affected by increasing alginate dosage. The highest Cu (95.82%) and Zn (97.33%) removal efficiencies were obtained by introducing 1 wt% alginate. Alginate can desorb Cu2+ and Zn2+ ions from soil by forming unstable gels, which could be dissociated through electrolysis. However, Pb2+ ions did not easily migrate out of the contaminated soil. The density functional theory (DFT) calculations show Pb2+ ions could form a more stable coordination sphere in metal complexes than Cu2+ and Zn2+ ions. The metal removal efficiency was decreased by increasing alginate dosage at a high level. More alginate could provide more carboxyl ligands for divalent metal ions to stabilize gels, which were difficult to dissociate by electrolysis. In summary, the results indicate it is potential for introducing alginate into an electrokinetic system to remediate Cu- and Zn- contaminated soil.


Assuntos
Recuperação e Remediação Ambiental , Metais Pesados , Poluentes do Solo , Metais Pesados/análise , Polieletrólitos , Solo , Poluentes do Solo/análise
2.
Food Chem ; 372: 131358, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-34655826

RESUMO

To improve the survivability of Lactobacillus rhamnosus probiotics, nanoliposomes (NLs) coated with chitosan (CH)-gelatin (GE) polyelectrolytes have been synthesized and characterized. The produced CH-GE-coated NLs containing L. rhamnosus had mean sizes in the range of 134.8-495.8 nm. HRTEM showed the smooth spherical shape of the vesicles. ATR-FTIR findings indicated the successful coating of the produced NLs by the used CH-GE polyelectrolytes. According to DSC results, CH-GE polyelectrolytes desorption on the surface of NLs altered the physical characteristics of the phospholipid bilayers. Here, an increase in the melting temperature (Tm) from 119.9 to 127.5 °C in L. rhamnosus-loaded CH-GE-coated NLs made this system more stable than uncoated liposomes. Furthermore, the CH-GE coated nanoparticles loaded with L. rhamnosus exhibited a significant enhancement in the viability of cells under simulated gastrointestinal fluids (SGF/SIF). These results may guide the potential application of polyelectrolytes-coated NLs as a carrier of probiotic cells in functional food development.


Assuntos
Quitosana , Lactobacillus rhamnosus , Nanopartículas , Probióticos , Lipossomos , Polieletrólitos
3.
J Colloid Interface Sci ; 605: 571-581, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34340041

RESUMO

Considering versatile potential applications of bioinspired membranes, we simulate the electrokinetic behavior of a cylindrical nanopore, surface modified by a polyelectrolyte (PE) layer. Taking account of the effect of electroosmotic flow and an additionally applied pH gradient, the influences of the strength of the pH gradient, the PE layer thickness, the length of the nanopore and its radius on its conductance and ion current rectification (ICR) performance are assessed. We show that if pHU (the pH at the higher pH end of the nanopore) is fixed at 11 and pHL (the pH at the lower pH end of the nanopore) varies from 3 to 11, the rectification factor Rf has a local maximum occurring in 6 < pHL <8; the greater the magnitude of the applied potential bias |V| the smaller the pHL at which the local maximum occurs. The influence of the PE layer thickness on the nanopore rectification performance is important only if 5 < pHL <8, and the optimum performance is reached at a medium thick PE layer (ca. 3 nm). Possible mechanisms associated with the ion transport phenomenon under consideration are proposed and discussed in detail.


Assuntos
Nanoporos , Eletro-Osmose , Concentração de Íons de Hidrogênio , Transporte de Íons , Polieletrólitos
4.
Methods Mol Biol ; 2414: 141-149, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34784036

RESUMO

A variety of delivery vehicles have been explored as adjuvanting/delivery platforms for peptide-based subunit vaccines. Polysaccharide-based systems have been found to be especially attractive due to their immune stimulating properties, biodegradability, biocompatibility, and low toxicity. Among them, chitosan and its derivatives are the most common cationic nanocarriers used for the delivery of antigens. Trimethyl chitosan (TMC) is a partially quaternized, water-soluble, and mucoadhesive derivative of chitosan. This chapter describes the preparation of a TMC-based polyelectrolyte complex as a delivery system for peptide subunit vaccines.


Assuntos
Polieletrólitos , Quitosana , Portadores de Fármacos , Nanopartículas , Peptídeos , Vacinas de Subunidades
5.
J Colloid Interface Sci ; 607(Pt 1): 153-162, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34506997

RESUMO

HYPOTHESIS: Polarity in polyelectrolyte multilayers (PEMs) may vary from the inner to the top layers of the film as the charge compensation of the layers is more effective inside the PEMs than in outer layers. Doxorubicin hydrochloride (DX) is used here to sense polarity at the single polyelectrolyte level inside PEMS. EXPERIMENTAL: DX is complexed electrostatically to a polyanion, either polystyrene sulfonate (PSS) or polyacrylic acid (PAA) and assembled at selected positions in a multilayer of the polyanion and polyallylamine hydrochloride (PAH) as polycation. Local polarity in the layer domain is evaluated through changes in the intensity ratio of the first to second band of spectra of DX (I1/I2 ratio) by steady state fluorescence, and by Lifetime fluorescence. FINDINGS: PAH/PSS multilayers, show a polarity similar to water with DX/PSS as top layer, decreasing to I1/I2 ratios similar to organic solvents as the number of polyelectrolyte layers assembled on top increases. For PAH/PAA multilayers, polarity values reflect a more polar environment than water when DX/PAA is the top layer, remaining unaltered by the assembly of polyelectrolyte layers on top. Results show that different polar environments may be present in a PEM when considering polarity at the single layer level.


Assuntos
Doxorrubicina , Água , Fluorescência , Fenômenos Físicos , Polieletrólitos
6.
Soft Matter ; 17(42): 9708-9715, 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34642718

RESUMO

Nowadays, several approaches are being suggested to endow hydrogels with improved mechanical properties for practical applications as cartilage and skin replacements, soft electronics, and actuators. However, it remains a challenge to develop DN gels with both high fracture toughness and fracture stretch. Here, we introduce (bio)polyelectrolyte complexes (PECs) consisting of gelatin and κ-carrageenan as the first brittle network and covalently crosslinked polyacrylamide (PAAm) as the second stretchable network to fabricate a highly stretchable and notch-insensitive gelatin/κ-carrageenan/PAAm hydrogel. The unprecedented high stretchability (∼51.7) is ascribed to the reduction of stress concentration and defects in the network structure through the fracture of the PEC gel. In addition, a high fracture toughness (∼16053.34 J m-2) is achieved by effective energy transfer between the PECs and PAAm gel due to their covalent crosslinking, and efficient energy dissipation through destroying inter- and intramolecular interactions in the PEC gel.


Assuntos
Gelatina , Hidrogéis , Resinas Acrílicas , Carragenina , Polieletrólitos
7.
Biomacromolecules ; 22(11): 4748-4757, 2021 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-34628859

RESUMO

Polyelectrolyte (PE) nanogels consisting of cross-linked PE networks integrate the advanced features of both nanogels and PEs. The soft environment and abundant intrinsic charges are of special interest for enzyme immobilization. However, the crucial factors that regulate enzyme encapsulation and activation remain obscure to date. Herein, we synthesized cationic poly (dimethyl aminoethyl methacrylate), PDMAEMA, nanogels with well-defined size and cross-link degrees and fully investigated the effects of different control factors on lipase immobilization. We demonstrate that the cationic PDMAEMA nanogels indeed enable efficient and safe loading of anionic lipase without disturbing their structures. Strong charge interaction achieved by tuning pH and larger particle size are favorable for lipase loading, while the enhanced enzymatic activity demands nanogels with smaller size and a moderate cross-link degree. As such, PDMAEMA nanogels with a hydrodynamic radius of 35 nm and 30% cross-linker fraction display the optimal catalytic efficiency, which is fourfold of that of free lipase. Moreover, the immobilization endows enhanced enzymatic activity in a broad scope of pH, ionic strength, and temperature, demonstrating effective protection and activation of lipase by the designed nanogels. Our study validates the crucial controls of the size and structure of PE nanogels on enzyme encapsulation and activation, and the revealed findings shall be helpful for designing functional PE nanogels and boosting their applications for enzyme immobilization.


Assuntos
Enzimas Imobilizadas , Lipase , Concentração de Íons de Hidrogênio , Nanogéis , Tamanho da Partícula , Polieletrólitos
8.
Mater Sci Eng C Mater Biol Appl ; 129: 112417, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34579926

RESUMO

Artificial biological scaffolds made of extracellular matrix (ECM) components, such as type I collagen, provide ideal physicochemical cues to various cell culture platforms. However, it remains a challenge to fabricate micrometer-sized ECM materials with precisely controlled morphologies that could reconstitute the 3-dimensional (3D) microenvironments surrounding cells. In the present study, we proposed a unique process to fabricate fragmented collagen microfibers using a microfluidic laminar-flow system. The continuous flow of an acidic collagen solution was neutralized to generate solid fibers, which were subsequently fragmented by applying a gentle shear stress in a polyanion-containing phosphate buffer. The morphology of the fiber fragment was controllable in a wide range by changing the type and/or concentration of the polyanion and by tuning the applied shear stress. The biological benefits of the fragmented fibers were investigated through the formation of multicellular spheroids composed of primary rat hepatocytes and microfibers on non-cell-adhesive micro-vessels. The microfibers enhanced the survival and functions of the hepatocytes and reproduced proper cell polarity, because the fibers facilitated the formation of cell-cell and cell-matrix interactions while modulating the close packing of cells. These results clearly indicated that the microengineered fragmented collagen fibers have great potential to reconstitute extracellular microenvironments for hepatocytes in 3D culture, which will be of significant benefit for cell-based drug testing and bottom-up tissue engineering.


Assuntos
Colágeno , Microfluídica , Animais , Matriz Extracelular , Hepatócitos , Polieletrólitos , Ratos , Engenharia Tecidual
9.
Langmuir ; 37(37): 11188-11193, 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34506141

RESUMO

Self-assembled lubricin (LUB) monolayers are an effective antiadhesive coating for biomedical applications. Long deposition times and limited control over the monolayer grafting density remain impediments to commercialization and applications in advanced sensor technologies. This work describes a novel potential pulse-facilitated coating method that reduces coating times to mere seconds while also providing high-level control over the achieved grafting density. This is the first time that the potential pulse-facilitated method is applied for direct assembling of a large and complex polyelectrolyte.


Assuntos
Glicoproteínas , Polímeros , Adsorção , Polieletrólitos
10.
Biomacromolecules ; 22(10): 4060-4083, 2021 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-34498457

RESUMO

Polyplex-mediated gene transfection is now in its' fourth decade of serious research, but the promise of polyplex-mediated gene therapy has yet to fully materialize. Only approximately one in a million applied plasmids actually expresses. A large part of this is due to an incomplete understanding of the mechanism of polyplex transfection. There is an assumption that internalization must follow a canonical mechanism of receptor mediated endocytosis. Herein, we present arguments that untargeted (and most targeted) polyplexes do not utilize these routes. By incorporating knowledge of syndecan-polyplex interactions, we can show that syndecans are the "target" for polyplexes. Further, it is known that free polycations (which disrupt cell-membranes by acid-catalyzed hydrolysis of phospholipid esters) are necessary for (untargeted) endocytosis. This can be incorporated into the model to produce a novel mechanism of endocytosis, which fits the observed phenomenology. After membrane translocation, polyplex containing vesicles reach the endosome after diffusing through the actin mesh below the cell membrane. From there, they are acidified and trafficked toward the lysosome. Some polyplexes are capable of escaping the endosome and unpacking, while others are not. Herein, it is argued that for some polycations, as acidification proceeds the polyplexes excluding free polycations, which disrupt the endosomal membrane by acid-catalyzed hydrolysis, allowing the polyplex to escape. The polyplex's internal charge ratio is now insufficient for stability and it releases plasmids which diffuse to the nucleus. A small proportion of these plasmids diffuse through the nuclear pore complex (NPC), with aggregation being the major cause of loss. Those plasmids that have diffused through the NPC will also aggregate, and this appears to be the reason such a small proportion of nuclear plasmids express mRNA. Thus, the structural features which promote unpacking in the endosome and allow for endosomal escape can be determined, and better polycations can be designed.


Assuntos
Endocitose , Plasmídeos/genética , Polieletrólitos , Transfecção
11.
ACS Biomater Sci Eng ; 7(10): 4898-4913, 2021 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-34533303

RESUMO

Cell encapsulation strategies using hydrogel beads have been considered as an alternative to immunosuppression in cell-based therapies. They rely on layer-by-layer (LbL) deposition of polymers to tune beads' permeability, creating a physical barrier to the host immune system. However, the LbL approach can also create diffusion barriers, hampering the flow of essential nutrients and therapeutic cell products. In this work, the polyelectrolyte complex (PEC) methodology was used to circumvent the drawbacks of the LbL strategy by inducing hydrogel bead formation through the interaction of anionic methacrylated gellan gum (GG-MA) with cationic poly-l-lysine (PLL). The interfacial complexation between both polymers resulted in beads with a cell-friendly GG-MA hydrogel core surrounded by a PEC semipermeable membrane. The beads showed great in vitro stability over time, a semi-permeable behavior, and supported human adipose-derived stem cell encapsulation. Additionally, and regarding immune recognition, the in vitro and in vivo studies pointed out that the hydrogel beads behave as an immunocompatible system. Overall, the engineered beads showed great potential for hydrogel-mediated cell therapies, when immunoprotection is required, as when treating different metabolic disorders.


Assuntos
Polilisina , Polissacarídeos Bacterianos , Humanos , Hidrogéis , Polieletrólitos
12.
Acta Biomater ; 135: 331-341, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34481054

RESUMO

The ability to coat scaffolds and wound dressings with therapeutic short interfering RNA (siRNA) holds much potential for applications in wound healing, cancer treatment, and regenerative medicine. Layer-by-layer (LbL) technology is an effective method to formulate polyelectrolyte thin films for local delivery of siRNA; however, the formation and efficacy of LbL coatings as drug delivery systems are highly contingent on the assembly conditions. Here, we investigate the effects of LbL assembly parameters on film composition and consequent siRNA-mediated gene knockdown efficiency in vitro. Films comprising poly(ß-amino ester) (PBAE) and siRNA were built on polyglactin 910 (Vicryl) sutures consisting of poly(10% L-lactide, 90% glycolide). A fractional factorial design was employed, varying the following LbL assembly conditions: pH, ionic strength, PBAE concentration, and siRNA concentration. Effects of these parameters on PBAE loading, siRNA loading, their respective weight ratios, and in vitro siRNA-mediated knockdown were elucidated. The parameter effects were leveraged to create a rationally designed set of solution conditions that was predicted to give effective siRNA-mediated knockdown, but not included in any of the original experimental conditions. This level of knockdown with our rationally designed loading conditions (47%) is comparable to previous formulations from our lab while being simpler in construction and requiring fewer film layers, which could save time and cost in manufacturing. This study highlights the importance of LbL solution conditions in the preparation of surface-mediated siRNA delivery systems and presents an adaptable methodology for extending these electrostatically-assembled coatings to the delivery of other therapeutic nucleic acids. STATEMENT OF SIGNIFICANCE: Short interfering RNA (siRNA) therapeutics are powerful tools to silence aberrant gene expression in the diseased state; however, the clinical utility of these therapies relies on effective controlled delivery approaches. Electrostatic self-assembly through the layer-by-layer (LbL) process enables direct siRNA release from surfaces, but this method is highly dependent upon the specific solution conditions used. Here, we use a fractional factorial design to illustrate how these assembly conditions impact composition of siRNA-eluting LbL thin films. We then elucidate how these properties mediate in vitro transfection efficacy. Ultimately, this work presents a significant step towards understanding how optimization of assembly conditions for surface-mediated LbL delivery can promote transfection efficacy while reducing the processing and material required.


Assuntos
Sistemas de Liberação de Medicamentos , Cicatrização , Polieletrólitos , RNA Interferente Pequeno , Transfecção
13.
Mater Sci Eng C Mater Biol Appl ; 128: 112258, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34474818

RESUMO

A novel polyelectrolyte nanocarrier was synthesized via layer-by-layer self-assembly of polycationic and polyanionic chains. The nanocarrier is composed of polyglutamate grafted chitosan core, dextran sulfate as a complexing agent, and polyethyleneimine shell decorated with folic acid. This polyelectrolyte complex has unique physicochemical properties so that the core is considered as an efficient carrier for LTX-315 and melittin peptides, and the shell is suitable for delivery of miR-34a. The spherical nanocarriers with an average size of 123 ± 5 nm and a zeta potential of -36 ± 1 mV demonstrated controlled-release of gene and peptides ensured a synergistic effect in establishing multiple cell death pathways on chemoresistance human breast adenocarcinoma cell line, MDA-MB-231. In vitro cell viability assays also revealed no cytotoxicity for the nanocarriers, and an IC50 of 15 µg/mL and 150 µg/mL for melittin and LTX-315, respectively, after 48 h, whereas co-delivery of melittin with miR-34a increased smart death induction by 54%.


Assuntos
Neoplasias da Mama , Quitosana , MicroRNAs/administração & dosagem , Nanopartículas , Neoplasias da Mama/tratamento farmacológico , Morte Celular , Linhagem Celular Tumoral , Feminino , Humanos , Meliteno/farmacologia , MicroRNAs/genética , Oligopeptídeos , Polieletrólitos
14.
Molecules ; 26(16)2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34443326

RESUMO

This work provides new insights from our team regarding advances in targeting canonical and non-canonical nucleic acid structures. This modality of medical treatment is used as a form of molecular medicine specifically against the growth of cancer cells. Nevertheless, because of increasing concerns about bacterial antibiotic resistance, this medical strategy is also being explored in this field. Up to three strategies for the use of DNA as target have been studied in our research lines during the last few years: (1) the intercalation of phenanthroline derivatives with duplex DNA; (2) the interaction of metal complexes containing phenanthroline with G-quadruplexes; and (3) the activity of Mo polyoxometalates and other Mo-oxo species as artificial phosphoesterases to catalyze the hydrolysis of phosphoester bonds in DNA. We demonstrate some promising computational results concerning the favorable interaction of these small molecules with DNA that could correspond to cytotoxic effects against tumoral cells and microorganisms. Therefore, our results open the door for the pharmaceutical and medical applications of the compounds we propose.


Assuntos
Ânions/química , Complexos de Coordenação/química , DNA/química , Quadruplex G , Fenantrolinas/química , Polieletrólitos/química , Ligantes
15.
J Chromatogr A ; 1654: 462460, 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34438303

RESUMO

With the growing concerns of polymer-grafted ion-exchange chromatography, the importance of protein adsorption on charged polymer-grafted surfaces cannot be stressed enough. However, a full understanding in adsorption in polymer brushes is still a great challenge due to the lack of in situ characterization technique. In this work, we use quartz crystal microbalance with dissipation to in situ investigate adsorption kinetics of γ-globulin and recombinant human lactoferrin on poly(3-sulfopropyl methacrylate) (pSPM) sensors prepared via atom transfer radical polymerization. With an increase of chain length and grafting density, great increasing amounts of proteins on pSPM-grafted sensors revealed that protein underwent a transition from monolayer to multilayer adsorption. It was attributed to direct protein binding into charged brushes, in which more binding sites involved and more coupled water lost. However, such a strong binding and rigid structure of proteins limited the protein transport in pSPM brushes and "chain delivery" effect. With an increase in grafting density, moreover, denser brushes hindered adjustment in protein conformation in pSPM brushes and further exacerbated protein transport in pSPM brushes. Furthermore, the influence of buffer pH and salt concentration further validated the ion exchange characteristics of protein adsorption into pSPM brushes. The research provided a variety of in situ evidence of protein binding and conformation evolution in pSPM brushes and elucidated mechanism of protein adsorption in pSPM brushes.


Assuntos
Cromatografia , Polieletrólitos , Polímeros , Proteínas , Técnicas de Microbalança de Cristal de Quartzo , Adsorção , Humanos , Cinética , Metacrilatos/química , Polieletrólitos/química , Polímeros/química , Proteínas/química , Propriedades de Superfície
16.
Biomacromolecules ; 22(9): 3913-3925, 2021 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-34347454

RESUMO

Proteoglycans (PGs) play many important roles in biology, contributing to the mechanical properties of tissues, helping to organize extracellular matrix components, and participating in signaling mechanisms related to mechanotransduction, cell differentiation, immune responses, and wound healing. Our lab has designed two different types of PG mimics: polyelectrolyte complex nanoparticles (PCNs) and PG-mimetic graft copolymers (GCs), both of which are prepared using naturally occurring glycosaminoglycans. This work evaluates the enzymatic stability of these PG mimics using hyaluronidases (I-S, IV-S, and II), chondroitinase ABC, and lysozyme, for PG mimics suspended in solution and adsorbed onto surfaces. Hyaluronan (HA)- and chondroitin sulfate (CS)-containing PG mimics are degraded by the hyaluronidases. PCNs prepared with CS and GCs prepared with heparin are the only CS- and HA-containing PG mimics protected from chondroitinase ABC. None of the materials are measurably degraded by lysozyme. Adsorption to polyelectrolyte multilayer surfaces protects PG mimics from degradation, compared to when PG mimics are combined with enzymes in solution; all surfaces are still intact after 21 days of enzyme exposure. This work reveals how the stability of PG mimics is controlled by both the composition and macromolecular assembly of the PG mimic and also by the size and specificity of the enzyme. Understanding and tuning these degradation susceptibilities are essential for advancing their applications in cardiovascular materials, orthopedic materials, and growth factor delivery applications.


Assuntos
Glicosaminoglicanos , Proteoglicanas , Sulfatos de Condroitina , Mecanotransdução Celular , Polieletrólitos
17.
AAPS PharmSciTech ; 22(7): 226, 2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34426942

RESUMO

The postprandial glycemic regulation is essential for diabetic patients to reduce the risk of long-term microvascular and macrovascular complications. Herein, we designed a glucose-responsive oral insulin delivery system based on polyelectrolyte complexes (PECs) for controlling the increasing postprandial glucose concentrations. Briefly, alginate-g-3-aminophenylboronic acid (ALG-g-APBA) and chitosan-g-3-fluoro-4-carboxyphenylboronic acid (CS-g-FPBA) were wrapped on mesoporous silica (MSN) to form the negative charged ALG-g-APBA@MSN and the positive charged CS-g-FPBA@MSN nanoparticles, with an optimum insulin loading capacity of 124 mg/g and 295 mg/g, respectively. ALG-g-APBA@MSN was further cross-linked with CS-g-FPBA@MSN to form PECs through electrostatic interaction and borate esters. The dense polyelectrolyte network wrapped on MSN was capable of preventing insulin from diffusion and regulating its release. The in vitro insulin release of PECs demonstrated an obvious glucose response profile in different glucose concentrations (0 mg/mL, 2 mg/mL, 5 mg/mL) and presented a switch "on" and "off" release regulation at hyperglycemic or normal state. The CCK-8 assay showed that none of the MSN, ALG-g-APBA@MSN, CS-g-FPBA@MSN, and PECs possessed cytotoxicity to Caco-2 cells. For in vivo tests, the oral PECs exhibited a significant hypoglycemic effect and maintained in the euglycemic levels up to approximately 12 h on diabetic rats. Overall, the PECs directly triggered by postprandial glucose in the intestine have a good potential to be applied in intelligent insulin delivery by the oral route.


Assuntos
Diabetes Mellitus Experimental , Glucose , Hipoglicemiantes , Insulina , Animais , Células CACO-2 , Diabetes Mellitus Experimental/tratamento farmacológico , Humanos , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Polieletrólitos , Ratos , Dióxido de Silício
18.
J Control Release ; 338: 71-79, 2021 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-34391834

RESUMO

Glucose-responsive insulin delivery systems have the potential to improve quality of life for individuals with diabetes by improving blood sugar control and limiting the risk of hypoglycemia. However, systems with desirable insulin release kinetics and high loading capacities have proven difficult to achieve. Here, we report the development of electrostatic complexes (ECs) comprised of insulin, a polycation, and glucose oxidase (GOx). Under normoglycemic physiological conditions, insulin carries a slight negative charge and forms a stable EC with the polycation. In hyperglycemia, the encapsulated glucose-sensing enzyme GOx converts glucose to gluconic acid and lowers the pH of the microenvironment, causing insulin to adopt a positive charge. Thus, the electrostatic interactions are disrupted, and insulin is released. Using a model polycation, we conducted molecular dynamics simulations to model these interactions, synthesized ECs with > 50% insulin loading capacity, and determined in vitro release kinetics. We further showed that a single dose of ECs can provide a glycemic profile in streptozotocin-induced diabetic mice that mimics healthy mice over a 9 h period with 2 glucose tolerance tests.


Assuntos
Diabetes Mellitus Experimental , Insulina , Animais , Glicemia , Glucose , Camundongos , Polieletrólitos , Qualidade de Vida
19.
Molecules ; 26(16)2021 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-34443385

RESUMO

DNA origami nanostructures (DONs) are promising substrates for the single-molecule investigation of biomolecular reactions and dynamics by in situ atomic force microscopy (AFM). For this, they are typically immobilized on mica substrates by adding millimolar concentrations of Mg2+ ions to the sample solution, which enable the adsorption of the negatively charged DONs at the like-charged mica surface. These non-physiological Mg2+ concentrations, however, present a serious limitation in such experiments as they may interfere with the reactions and processes under investigation. Therefore, we here evaluate three approaches to efficiently immobilize DONs at mica surfaces under essentially Mg2+-free conditions. These approaches rely on the pre-adsorption of different multivalent cations, i.e., Ni2+, poly-l-lysine (PLL), and spermidine (Spdn). DON adsorption is studied in phosphate-buffered saline (PBS) and pure water. In general, Ni2+ shows the worst performance with heavily deformed DONs. For 2D DON triangles, adsorption at PLL- and in particular Spdn-modified mica may outperform even Mg2+-mediated adsorption in terms of surface coverage, depending on the employed solution. For 3D six-helix bundles, less pronounced differences between the individual strategies are observed. Our results provide some general guidance for the immobilization of DONs at mica surfaces under Mg2+-free conditions and may aid future in situ AFM studies.


Assuntos
Silicatos de Alumínio/química , DNA/química , Magnésio/química , Microscopia de Força Atômica , Nanoestruturas/química , Conformação de Ácido Nucleico , Adsorção , Níquel/química , Polieletrólitos/química , Polilisina/química , Espermidina/química , Propriedades de Superfície , Água/química
20.
Int J Mol Sci ; 22(15)2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34360724

RESUMO

The formation of coffee-ring deposits upon evaporation of sessile droplets containing mixtures of poly(diallyldimethylammonium chloride) (PDADMAC) and two different anionic surfactants were studied. This process is driven by the Marangoni stresses resulting from the formation of surface-active polyelectrolyte-surfactant complexes in solution and the salt arising from the release of counterions. The morphologies of the deposits appear to be dependent on the surfactant concentration, independent of their chemical nature, and consist of a peripheral coffee ring composed of PDADMAC and PDADMAC-surfactant complexes, and a secondary region of dendrite-like structures of pure NaCl at the interior of the residue formed at the end of the evaporation. This is compatible with a hydrodynamic flow associated with the Marangoni stress from the apex of the drop to the three-phase contact line for those cases in which the concentration of the complexes dominates the surface tension, whereas it is reversed when most of the PDADMAC and the complexes have been deposited at the rim and the bulk contains mainly salt.


Assuntos
Polieletrólitos/química , Polietilenos/química , Compostos de Amônio Quaternário/química , Silício/química , Tensoativos/química , Tensão Superficial
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