RESUMEN

Polymer nanogels-considered as nanoscale hydrogel particles-are attractive for biological and biomedical applications due to their unique physicochemical flexibility. However, the aggregation or accumulation of nanoparticles in the body or the occurrence of the body's defense reactions still pose a research challenge. Here, we demonstrate the fabrication of degradable nanogels using thermoresponsive, cytocompatible poly[oligo(ethylene glycol) methacrylate]s-based copolymers (POEGMA). The combination of POEGMA's beneficial properties (switchable affinity to water, nontoxicity, non-immunogenicity) along with the possibility of nanogel degradation constitute an important approach from a biological point of view. The copolymers of oligo(ethylene glycol) methacrylates were partially modified with short segments of degradable oligo(lactic acid) (OLA) terminated with the acrylate group. Under the influence of temperature, copolymers formed self-assembled nanoparticles, so-called mesoglobules, with sizes of 140-1000 nm. The thermoresponsive behavior of the obtained copolymers and the nanostructure sizes depended on the heating rate and the presence of salts in the aqueous media. The obtained mesoglobules were stabilized by chemical crosslinking via thiol-acrylate Michael addition, leading to nanogels that degraded over time in water, as indicated by the DLS, cryo-TEM, and AFM measurements. Combining these findings with the lack of toxicity of the obtained systems towards human fibroblasts indicates their application potential.

RESUMEN

The aim of this investigation was to prepare novel hybrid materials with enhanced antimicrobial properties to be used in food preservation and packaging applications. Therefore, nanocomposite materials were synthesized based on two stimuli-responsive oligo(ethylene glycol methacrylate)s, namely PEGMA and PEGMEMA, the first bearing hydroxyl side groups with three different metal nanoparticles, i.e., Ag, TiO2 and ZnO. The in situ radical polymerization technique was employed to ensure good dispersion of the nanoparticles in the polymer matrix. FTIR spectra identified the successful preparation of the corresponding polymers and XRD scans revealed the presence of the nanoparticles in the polymer matrix. In the polymer bearing hydroxyl groups, the presence of Ag-NPs led to slightly lower thermal stability as measured by TGA, whereas both ZnO and TiO2 led to nanomaterials with better thermal stability. The antimicrobial activity of all materials was determined against the Gram-negative bacteria E. coli and the Gram-positive S. aureus, B. subtilis and B. cereus. PEGMEMA nanocomposites had much better antimicrobial activity compared to PEGMA. Ag NPs exhibited the best inhibition of microbial growth in both polymers with all four bacteria. Nanocomposites with TiO2 showed a very good inhibition percentage when used in PEGMEMA-based materials, while in PEGMA material, high antimicrobial activity was observed only against E. coli and B. subtilis, with moderate activity against B. cereus and almost absent activity against S. aureus. The presence of ZnO showed antimicrobial activity only in the case of PEGMEMA-based materials. Differences observed in the antibacterial activity of the polymers with the different nanoparticles could be attributed to the different structure of the polymers and possibly the more efficient release of the NPs.

RESUMEN

The thermal behavior and aggregation process of the poly(N-isopropyl acrylamide), poly[oligo(ethylene glycol) methyl ether methacrylate], and poly[(2-hydroxyethyl methacrylate)-co-oligo(ethylene glycol) methyl ether methacrylate] thermoresponsive polymers were studied in a commonly used Dulbecco's Modified Eagle Medium (DMEM) cell culture medium and solutions of its individual components in the same concentration as found in DMEM. All studied copolymers exhibited an unexpected transmittance profile in the DMEM. During heating above the cloud point temperature (TCP), the polymers additionally aggregated, which led to the formation of their precipitates. The behavior of the polymers was further studied to evaluate how individual salts affected the transition temperature, size (Dh), and stability of the polymer particles. Organic additives, such as amino acids and glucose, had a significantly lesser impact on the thermoresponsive aggregation of the polymers than inorganic ones. Changes to the TCP were small and the formation of precipitates was not observed. The presence of small amounts of amino acids caused a decrease in the polymer aggregate sizes. Obtained results are of utmost importance in thermoresponsive drug nanocarrier studies.

RESUMEN

While hydrogels are demonstrated to be effective scaffolds for soft tissue engineering, existing fabrication techniques pose limitations in terms of being able to reproduce both the micro/nanofibrous structures of native extracellular matrix as well as the spatial arrangement of different cell types inherent of more complex tissues. Herein, a reactive cell electrospinning strategy is described using hydrazide and aldehyde-functionalized poly(oligoethylene glycol methacrylate) precursor polymers that can create nanofibrous hydrogel scaffolds with controllable local cell gradients using a sequential all-aqueous process that does not require additives or external energy. Cells can be encapsulated directly during the fabrication process in different layers within the scaffold, enabling localized segregation of different cell types within the structures without compromising their capacity to proliferate (≈4-fold increase in cell density over a 14 day incubation period). This sequential reactive electrospinning approach thus offers promise to generate coculture fibrous hydrogel networks in which both the nanoscale architecture and the cell distribution can be controlled, as it is essential to recreate more complex types of tissues.

RESUMEN

In this study, we developed an enzyme- and pH-responsive dendronized poly(oligo-(ethylene glycol) methacrylate) (pOEGMA)-doxorubicin (DOX) polymeric prodrug, which combined the pOEGMA structure with a degradable peptide dendron. The introduction of the dendron in the prodrug hindered the entanglement of brush oligo-(ethylene glycol) (OEG) chains, allowed the prodrug to possess dual stimuli-responsiveness, and mediated self-assembly of the polymeric prodrug to form stable nanoparticles (NPs). Brush conformation of polyethylene glycol (PEG) side chains endowed the NPs with long-term circulation with a half-life of 16.0 h. The dual-responsive dendritic structure enhanced cellular uptake of NPs and facilitated drug release in response to overexpressed cathepsin B and an acidic pH in the tumor microenvironment, resulting in an enhanced therapeutic effect with a tumor inhibition rate of 72.9% for 4T1 tumor-bearing mice. The NPs were demonstrated to possess great hemocompatibility and biosafety. Therefore, this strategy could provide great insight for the design of poly(oligo-(ethylene glycol) methacrylate)-based copolymers as drug delivery carriers. STATEMENT OF SIGNIFICANCE: We propose a dual-stimuli-responsive dendronized strategy for improving the cancer therapeutic effect of the poly(oligo-(ethylene glycol) methacrylate) (pOEGMA)-based drug conjugates. The introduction of the functional dendron promotes self-assembly of the polymeric prodrug into nanoparticles, hindering the entanglement of brush oligo-(ethylene glycol) (OEG) chains in the conjugated drugs. The obtained poly OEGMA-GFLG-Dendron-NH-N=DOX nanoparticles maintains long circulation, while addresses the drug release issue due to the presence of high-density PEG. The drug delivery system exhibits a high therapeutic potentcy with negligible side effects.

Asunto(s)

RESUMEN

Poly(dimethylsiloxane) (PDMS) elastomer is now a well-known material for packaging implantable biomedical micro-devices owing to unique bulk properties such as biocompatibility, low toxicity, excellent rheological properties, good flexibility, and mechanical stability. Despite the desirable bulk characteristics, PDMS is generally regarded as a high-flux material for oxygen and water vapor to penetrate compared with other polymeric barrier materials, which is related to the defect-induced penetration through the packaging coating prepared by the traditional deposition techniques. Besides, its hydrophobic nature causes serious fouling problems and limits the practical application of PDMS-based devices. In this work, the performance of silicone thin films as a packaging layer was improved by the fabrication of the roller-casted multiple thin layers to minimize a defect-induced failure. To confer hydrophilicity and cell fouling resistance, high-density and well-defined poly(oligo(ethylene glycol) methacrylate) (POEGMA) brushes were tethered via the surface-initiated atom transfer radical polymerization (SI-ATRP) technique on the roller-casted multiple thin PDMS layers. The characteristics of fabricated substrates were determined by static water contact angle measurement, X-ray photoelectron spectroscopy, and attenuated total reflection-Fourier transform infrared spectroscopy. In vitro cell behavior of POEGMA-grafted PDMS substrates was evaluated to examine cell-fouling resistance.

Asunto(s)

RESUMEN

Thermoresponsive polymers are a promising material for drug nanocarrier preparation, which makes the study of their aggregation in physiological conditions very important. In this paper, the thermal behaviour of the thermoresponsive polymers poly(N-isopropylacrylamide), poly(2-isopropyl-2-oxazoline-co-2-n-propyl-2-oxazoline) and poly[(2-hydroxyethyl methacrylate)-co-oligo(ethylene glycol) methyl ether methacrylate] were studied in phosphate buffer (PBS) and solutions of its salts in concentration as in PBS. The thermal response of the polymers was measured using UV-Vis and dynamic light scattering (DLS). The salts shifted the cloud point temperature (TCP) of the (co)polymers to higher values compared to the TCP of aqueous polymer solutions. In PBS and NaCl solutions, all polymers exhibited an unexpected and previously unreported transmittance profile. During heating, an additional aggregation of polymers appeared above the TCP accompanied by the formation of a precipitate. In monosodium phosphate solutions and pure water, the studied polymers showed lower critical solution temperature (LCST-type) behaviour. DLS measurements showed that a salt influenced the size of the resulting polymer particles. The sizes and stability of particles depended on the heating rate. In PBS and NaCl solutions, the size of particles in the dispersion decreased above 60 °C, and the precipitate appeared on the bottom of the cuvette. The additional aggregation of polymer and its falling out of solution may hinder the removal of carriers from the body and has to be taken into account when preparing nanocarriers.

RESUMEN

Thermo-responsive copolymers based on oligo(ethylene glycol) methacrylate (OEGMA, Mn = 300 g/mol) and pentafluorostyrene (PFS), coded PFG, were synthesized by RAFT polymerization, using a trithiocarbonate (CTTPC) as controlling agent. Different molar masses were targeted and dispersities lower than 1.51 were obtained. The thermally triggered self-assembly of the resulting PFG copolymers in water was investigated by dynamic light scattering (DLS). The lower critical solution temperature (LCST) slightly increased with the molecular weight in the 26-30 °C temperature range, whereas the sizes of the intermicellar aggregates formed upon self-assembly tended to decrease with increasing molecular weights (ranging from 1415 to 572 nm). The resulting thermally-induced polymer aggregates were then used to encapsulate and remove organic contaminants from water. Nile Red (NR) and Thiazole yellow G (TYG) were employed as hydrophobic and hydrophilic model contaminants, respectively. Experimental results evidenced that higher molecular weight copolymers removed up to 90% of NR from aqueous solution, corresponding to about 10 mg of dye per g of copolymer, regardless of NR concentration. The removal of TYG was lower with respect to NR, decreasing from about 40% to around 20% with TYG concentration. Finally, the copolymers were shown to be potentially recycled and reused in the treatment of contaminated water.

RESUMEN

A series of copolymers of di(ethylene glycol) methyl ether methacrylate (D) and 2-aminoethyl methacrylate (A) (P(D-co-A)) with variable ratios of comonomers were synthesized using atom transfer radical polymerization. Then, the amino groups of obtained copolymers were modified to clickable azide or prop-2-yn-1-yl carbamate groups. A thermoresponsive copolymers were obtained with the value of cloud point temperature (TCP) dependent on the type and number of functional groups in the copolymer and on the concentration of solutions. For P(D-co-A) copolymers, the TCP increased with increasing content of 2-aminoethyl methacrylate comonomer. The presence of azide and prop-2-yn-1-yl carbamate groups caused the changes of TCP of modified copolymers. All studied copolymers in dilute aqueous solutions aggregated above TCP to nanoparticles with sizes dependent on the solution concentration, heating procedures, and types and numbers of functional groups present in a copolymer chain. The presence of hydrophilic elements in the chain and the increase in the copolymer concentration led to the enlargement of the particle sizes. Aggregates were crosslinked using click reaction between an azide and prop-2-yn-1-yl carbamate groups that led to stable thermoresponsive nanogels. A systematic study of the behavior of copolymers allowed the determination of the chains useful for possible application in drug delivery.

RESUMEN

In this work, well-defined poly(dimethylsiloxane)-b-poly(oligo (ethylene glycol) methacrylate) (PDMS-b-POEGMA) amphiphilic block copolymers were synthesized and their effect on human dermal fibroblast were investigated. Anionic ring opening polymerization (ROP) and atom transfer radical polymerization (ATRP) were used to synthesis the block copolymers. The molecular weight of synthesized copolymers ranged from 1000 to 2300 Da by changing the number of both PDMS and POEGMA units. It was found that the copolymer having low molecular weight decreased the fibroblast viability and proliferation by inducing apoptosis. It was proved by flow cytometry and TUNEL assay that human dermal fibroblast experienced apoptosis after exposure to synthesized amphiphilic copolymers. The results of this work suggest the use of PDMS-b-POEGMA amphiphilic copolymers with low molecular weight for hypertrophic scars remediation.

Asunto(s)

RESUMEN

Herein, we report on a robust approach to fabricate antibacterial nanocomposite coating simply by immersing poly(oligo(ethylene glycol) methacrylate) (POEGMA) brush into a silver perchlorate solution without using any external reducing agents. The POEGMA brush of 48.3 nm in thickness is prepared via surface-initiated atom transfer radical polymerization method. Field-emission scanning electron microscope and Raman measurements indicate that silver nanoparticles of 14 ∼ 25 nm in diameter are successfully embedded into the POEGMA brush. Antibacterial activities of the resultant silver-loaded POEGMA brushes against both Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus are measured by zone of inhibition and colony-counting methods, respectively. The results show that the silver-loaded POEGMA coatings exhibit enhanced antibacterial efficiency compared to bare POEGMA brush. In order to elucidate their antibacterial mechanism, silver release behaviors of these silver-loaded POEGMA brushes are monitored via inductively coupled plasma mass spectrometry.

Asunto(s)

RESUMEN

Thermoresponsive polymers have received significant research attention as smart materials with particular interest in biomedical applications. The composition and architecture are known to strongly influence the thermoresponsive properties of the materials. For example, the strong overlap of end-grafted polymer chains in polymer brushes leads to a broader collapse transition relative to linear ungrafted chains as well as temperature dependent adhesion. The temperature response of free polymer has been widely reported to depend on the concentration and identity of ions in solution and is further modified by the composition of the solvent and presence of cosolutes. However, the influence of polymer architecture on these specific ion effects is relatively unknown. Herein, we compare the current understanding of specific ion effects on free polymer chains and gels with recent studies of polymer brushes. Further studies on mixed salt systems are found to be the next step to predicting the behaviour of these materials in biological systems.

RESUMEN

The thermoresponse of poly(di(ethyleneglycol) methyl ether methacrylate) (PMEO2MA) brushes has been investigated in the presence of monovalent anions at either end of the Hofmeister series using ellipsometry, neutron reflectometry (NR) and colloid probe atomic force microscopy (AFM). NR measurements in deuterium oxide showed no evidence of vertical phase separation perpendicular to the grafting substrate with a gradual transition between a block-like, dense structure at 45°C and an extended, dilute conformation at lower temperatures. All three techniques revealed a shift to a more collapsed state for a given temperature in kosmotropic potassium acetate solutions, while more swollen structures were observed in chaotropic potassium thiocyanate solutions. No difference was observed between 250mM and 500mM thiocyanate for a 540Å brush studied by ellipsometry, while the lower molecular weight ∼200Å brushes used for NR and AFM measurements continued to respond with increasing salt concentration. The effect of thiocyanate on the temperature response was greatly enhanced relative to PNIPAM with the shift in temperature response at 250mM being five times greater than a PNIPAM brush of similar thickness and grafting density.

Asunto(s)

RESUMEN

Purification of virus-like particles (VLPs) in bind-and-elute mode has reached a bottleneck. Negative chromatography has emerged as the alternative solution; however, benchmark of negative chromatography media and their respective optimized conditions are absent. Hence, this study was carried out to compare the performance of different negative chromatography media for the purification of hepatitis B VLPs (HB-VLPs) from clarified Escherichia coli feedstock. The modified anion exchange media, core-shell adsorbents (InertShell and InertLayer 1000) and polymer grafted adsorbents (SQ) were compared. The results of chromatography from packed bed column of core-shell adsorbents showed that there is a trade-off between the purity and recovery of HB-VLPs in the flowthrough fraction due to the shell thickness. Atomic force microscopic analysis revealed funnel-shaped pore channels in the shell layer which may contribute to the entrapment of HB-VLPs. A longer residence time at a lower feed flow rate (0.5ml/min) improved slightly the HB-VLPs purity in all modified adsorbents, but the recovery in InertShell reduced substantially. The preheat-treatment is not recommended for the negative chromatography as the thermal-induced co-aggregation of HCPs and HB-VLPs would flow along with HB-VLPs and thus reduced the HB-VLPs purity in the flowthrough. Further reduction in the feedstock concentration enhanced the purity of HB-VLPs especially in InertLayer 1000 but reduced substantially the recovery of HB-VLPs. In general, the polymer grafted adsorbent, SQ, performed better than the core-shell adsorbents in handling a higher feedstock concentration.

Asunto(s)

RESUMEN

Poly(oligo(ethylene glycol) methacrylate) (POEGMA), an inert polymer was grafted onto an anion exchange adsorbent for the exclusion of relatively larger hepatitis B virus-like particles (HB-VLPs) from the anion exchange ligand (Q) and at the same time this process allowed the selective adsorption of smaller size Escherichia coli host cell proteins (HCPs). The chain lengths of the POEGMA grafted were modulated by varying the amount of monomers used in the polymer grafting. The purification factor and yield of the HB-VLPs obtained from the flow-through of negative chromatography were 2.3 and 66.0±3.1%, respectively, when shorter chain length of POEGMA (SQ) was grafted. Adsorbent grafted with longer chain of POEGMA (LQ) excluded some HCPs that are larger in size together with the HB-VLPs, reducing the purity of the recovered HB-VLPs. Further heat-treatment of the flow-through pool from SQ followed by centrifugation increased the purity of heat stable HB-VLPs to 87.5±1.1%. Heat-treatment of the flow through sample resulted in thermal denaturation and aggregation of HCPs, while the heat stable HB-VLPs still remained intact as observed under a transmission electron microscope. The performance of the negative chromatography together with heat treatment in the purification of HB-VLPs is far better than the reported bind-and-elute techniques.

Asunto(s)

RESUMEN

Novel thermosensitive nanocomposite (NC) hydrogels consisting of organic/inorganic networks are prepared via in situ free radical polymerization of 2-(2-methoxyethoxy) ethyl methacrylate (MEO2 MA) and oligo(ethylene glycol) methacrylate (OEGMA) in the presence of inorganic cross-linker clay in aqueous solution. The obtained clay/P(MEO2 MA-co-OEGMA) hydrogels exhibit double volume phase transition temperatures, an upper critical solution temperature (UCST), and a lower critical solution temperature (LCST), which can be controlled between 5 and 85 °C by varying the fraction of OEGMA units and the weight percentage of cross-linker clay. These new types of NC hydrogels with excellent reversible thermosensitivity are promising for temperature-sensitive applications such as smart optical switches.

Asunto(s)