Hydrogel Research Articles

Recent advances in polymeric hydrogel nanoarchitectures for drug delivery applications

Hydrogels (HDG) are materials exhibiting versatile applications in varying fields such as the pharmaceutical and biomedical industries. However, HDG are prone to inferior chemical, biological, electrical and mechanical features. In order to mitigate these deficiencies, the advent of nanotechnology has informed the inclusion of multifunctional nanoparticulates within HDG matrices to garnerior superior features. Thus, polymeric hydrogel nanoarchitectures (PHN) are amongst emerging category of new nano-hydrogels, fabricated through the incorporation of nanoparticulates, as a second phase within HDG, with enhanced and enchanting properties. For effective pharmaceutical applications, the prevalence of pores within the PHN is outstanding for drug delivery systems (DDS) because of the feasibility of conveying active entities and releasing them at a controlled rate through varying mechanisms. The outstanding behavior of PHN to up-take elevated levels of water transforms them to immune-tolerant nanomaterials thereby making them attractive for biologically affiliated applications, especially in field of pharmacy for drug delivery application. Therefore, this paper presents recently emerging advancements in drug delivery applications of PHN and HDG derivatives including macrogels microgels, and nanogels. Furthermore, magnetically responsive HDG, “smart” or “intelligent” HDG as DDS are also presented. They HDG materials preparation, characterization, properties and applications as DDS are elaborately elucidated as well.

Preparation and Properties of Double-Crosslinked Hydroxyapatite Composite Hydrogels.

Natural polymer hydrogels have good mechanical properties and biocompatibility. This study designed hydroxyapatite-enhanced photo-oxidized double-crosslinked hydrogels. Hyaluronic acid (HA) and gelatin (Gel) were modified with methacrylate anhydride. The catechin group was further introduced into the HA chain inspired by the adhesion chemistry of marine mussels. Hence, the double-crosslinked hydrogel (HG) was formed by the photo-crosslinking of double bonds and the oxidative-crosslinking of catechins. Moreover, hydroxyapatite was introduced into HG to form hydroxyapatite-enhanced hydrogels (HGH). The results indicate that, with an increase in crosslinking network density, the stiffness of hydrogels became higher; these hydrogels have more of a compact pore structure, their anti-degradation property is improved, and swelling property is reduced. The introduction of hydroxyapatite greatly improved the mechanical properties of hydrogels, but there is no change in the stability and crosslinking network structure of hydrogels. These inorganic phase-enhanced hydrogels were expected to be applied to tissue engineering scaffolds.

Fmoc-Diphenylalanine Hydrogels: Optimization of Preparation Methods and Structural Insights.

Hydrogels (HGs) are tri-dimensional materials with a non-Newtonian flow behaviour formed by networks able to encapsulate high amounts of water or other biological fluids. They can be prepared using both synthetic or natural polymers and their mechanical and functional properties may change according to the preparation method, the solvent, the pH, and to others experimental parameters. Recently, many short and ultra-short peptides have been investigated as building blocks for the formulation of biocompatible hydrogels suitable for different biomedical applications. Due to its simplicity and capability to gel in physiological conditions, Fmoc-FF dipeptide is one of the most studied peptide hydrogelators. Although its identification dates to 15 ago, its behaviour is currently studied because of the observation that the final material obtained is deeply dependent on the preparation method. To collect information about their formulation, here are reported some different strategies adopted until now for the Fmoc-FF HG preparation, noting the changes in the structural arrangement and behaviour in terms of stiffness, matrix porosity, and stability induced by the different formulation strategy on the final material.

Injectable hydrogel as a carrier of vancomycin and a cathelicidin-derived peptide for osteomyelitis treatment.

A local drug delivery system that attempts to find a suitable balance between antimicrobial and regenerative actions was developed for osteomyelitis treatment (OM). This system combines the angiogenic and immunomodulatory peptide LLKKK18 (LL18) and vancomycin hydrochloride (VH), loaded into an injectable oxidized dextrin (ODEX)-based hydrogel (HG). In vitro cytotoxicity was analyzed in MC3T3-E1 pre-osteoblasts and erythrocytes. The kinetics of LL18 release was studied. Antimicrobial activity was assessed in vitro against a clinical Methicillin-Resistant Staphylococcus aureus (MRSA) strain. A rat model of acute OM was developed by direct inoculation into a tibia defect, concomitantly with the implantation of the drug-loaded HG. The local bioburden was quantified and damage in surrounding tissues was examined histologically. In vitro, ODEX-based HG displayed a safe hemolytic profile. Half of LL18 (53%) is released during the swelling phase at physiological pH, then being gradually released until complete HG degradation. LL18-loaded HG at 300 μM was the most effective peptide formulation in decreasing in vivo infection among concentrations ranging from 86 to 429 μM. The histopathological scores observed in vivo varied with the LL18 concentration in a dose-dependent manner. VH at 28 mM completely eradicated bacteria, although with substantial tissue injury. We have found that sub-millimolar doses of VH combined with LL18 at 300 μM may suffice to eradicate the infection, with reduced tissue damage. We propose an easy-to-handle, shape-fitting HG formulation with the potential to treat MRSA-infected bone with low VH doses associated with LL18.

Smart hydrogel with rapid self-healing and controlled release attributes for biomedical applications

A novel shear-thinning cross-linked hydrogel (HG) of polyvinyl alcohol and guar gum has been developed. The HG exhibited a fast self-healing ability within 60 s to bear deformation and possessed excellent stretchability and thermoresponsive properties. The HG was loaded with AgNPs using the in-situ cross-linking method to form the HG composite (HGC). SEM study revealed that the surface of the HG transformed from a dense and non-porous structure to an unordered and porous structure in the HGC suitable for immobilization of the AgNPs. X-ray photoelectron spectroscopy deconvolution study confirmed the presence of silver in the HGC. The cumulative release of silver nanoparticles from HGC was investigated and found that about 15% of the loaded Ag is released over five days. Ag release data fitment to various mathematical models specified that the Ag release profile is explained best by the Korsmeyer–Peppas model which revealed that the release of Ag from the HG was mainly administered by diffusion. The diffusion constant was calculated to be 5.1 cm2 s−1, indicative of an excellent controlled release system. The synthesized HGC can exhibit antibacterial activity on both gram-positive and gram-negative bacteria. The release mechanism and effective antibacterial activity support the synergic structure-property correlation of the HG and HGC.

Wet Electrospun Nanofibers-Fortified Gelatin/Alginate-Based Nanocomposite as a Single-Dose Biomimicking Skin Substitute

We report the development and evaluation of a series of well-designed single-dose extracellular matrix (ECM)-mimicking nanofibers (NFs)-reinforced hydrogel (HG)-based skin substitute for wound healing. The HG matrix of the proposed skin substitute is composed of gelatin (GE) and sodium alginate (SA), and incorporates hyaluronic acid (HA) as a key component of the natural ECM, as well as the antimicrobial Punica granatum extract (PE). This HG nanocomposite was cross-linked by the biocompatible N-(3-(dimethylamino)propyl)-N'-ethylcarbodiimide hydrochloride (EDC) cross-linker, and was reinforced with fragmented trans-ferulic acid (FA)-loaded cellulose acetate/polycaprolactone (PCL/CA) NFs. The NFs were obtained via wet electrospinning into a poly(vinyl alcohol) (PVA) coagulating solution to closely resemble the porous structure of the ECM fibers, which facilitates cell migration, attachment, and proliferation. The proposed design of the skin substitute allows adjustable mechanical characteristics and outstanding physical properties (swelling and biodegradability), as well as an excellent porous microstructure. The developed skin substitutes were characterized using Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), and electron microscopy. In addition, the biodegradability, biocompatibility, bioactivity, mechanical, and in vitro drug release characteristics were investigated. Moreover, an in vivo excisional full-thickness defect model was conducted to assess skin regeneration and healing effectiveness. The average diameters of the plain and FA-loaded NFs are 210 ± 12 nm and 452 ± 25 nm, respectively. The developed ECM-mimicking skin substitutes demonstrated good antibacterial activity, free-radical scavenging activity, cytocompatibility, porosity, water absorption ability, and good biodegradability. In vivo application of the ECM-mimicking skin substitutes revealed their excellent wound-healing activity and their suitability for single-dose treatment of deep wounds with reducing the wound diameter to 0.95 mm after 15 days of treatment. Moreover, the histological investigation of the wound area demonstrated that the applied skin substitutes have not only enhanced the wound healing progress, but also can participate in improving the quality of the regenerated skin in the treated area via facilitating collagen fibers regeneration and deposition.

Smart and eco-friendly N-isopropylacrylamide and cellulose hydrogels as a safe dual-drug local cancer therapy approach

Local cancer treatment by in situ injections of thermo-responsive hydrogels (HG) offers several advantages over conventional systemic anti-cancer treatments. In this work, a biodegradable and multicompartmental HG composed of N-isopropylacrylamide, cellulose, citric acid, and ceric ammonium nitrate was developed for the controlled release of hydrophilic (doxorubicin) and hydrophobic (niclosamide) drugs. The formulation presented ideal properties regarding thermo-responsiveness, rheological behavior, drug release profile, biocompatibility, and biological activity in colon and ovarian cancer cells. Cellulose was found to retard drugs release rate, being only 4 % of doxorubicin and 30 % of niclosamide released after 1 week. This low release was sufficient to cause cell death in both cell lines. Moreover, HG demonstrated a proper injectability, in situ prevalence, and safety profile in vivo. Overall, the HG properties, together with its natural and eco-friendly composition, create a safe and efficient platform for the local treatment of non-resectable tumors or tumors requiring pre-surgical adjuvant therapy.

Biopolymeric composite hydrogel loaded with silver NPs and epigallocatechin gallate (EGCG) effectively manages ROS for rapid wound healing in type II diabetic wounds

Delayed wound healing in patients having type-II diabetes mellitus (T2DM) often results in a high rate of amputation. We report an innovative Guar Gum-based macroporous hydrogel (HG) infused with an antibacterial agent (Ag NPs), and antioxidant, epigallocatechin gallate (EGCG) to address rapid wound healing and interestingly could inhibit the associated pathophysical bone infection in a high-fat-diet-induced T2DM C57BL/6 mice model. The HG-Ag-EGCG elicits scar-free wound healing in subcutaneous wounds and histopathological evidence confirmed HG-Ag-EGCG hydrogel patch elicits better wound healing through enhanced cell proliferation, mature connecting tissue fiber formation, minimum void spaces formation, and better re-epithelialization when compared with a market available hydrogel patch material (Luofucon®). Supportive of the in vivo outcomes, in vitro experiments delineated better-wound closure due to improved management of ROS by the HG-Ag-EGCG. Additionally, a favorable non-toxicity outcome assessed through both in vitro and in vivo conditions confirmed its potential applicability in clinical wound care management.

Synthesis and Swelling Behavior of Poly (N-tert-amylacrylamide-co-acrylamide / AcNa) Hydrogels

The poly(N-tert-amylacrylamide-co-acrylamide/AcNa)hydrogel was synthesized by free radical copolymeristion in water/methanol medium using Ammonium per sulphate as the initiator and N,N-methylenebisacrylamide as a crosslinker at 60oC.The amount of N-tertamylacrylamide(NTA) and Acrylamide(AM) were fixed and the amount of sodium acrylate was varied.The Hydro gels were characterized by 1H-NMR ,13C-NMR and IR Spectroscopy.The swelling behavior of hydrogels was studied by gravimetric method and degree of swelling was increased by increasing the amount of AcNa.The surface morphology was studied by SEM analysis. Keywords: N-tert-amylacrylamide,AcNa,Hydrogels,Swelling behavior

Fast-Forming Dissolvable Redox-Responsive Hydrogels: Exploiting the Orthogonality of Thiol–Maleimide and Thiol–Disulfide Exchange Chemistry

Fast-forming yet easily dissolvable hydrogels (HGs) have potential applications in wound healing, burn incidences, and delivery of therapeutic agents. Herein, a combination of a thiol–maleimide conjugation and thiol–disulfide exchange reaction is employed to fabricate fast-forming HGs which rapidly dissolve upon exposure to dithiothreitol (DTT), a nontoxic thiol-containing hydrophilic molecule. In particular, maleimide disulfide-terminated telechelic linear poly(ethylene glycol) (PEG) polymer and PEG-based tetrathiol macromonomers are employed as gel precursors, which upon mixing yield HGs within a minute. The selectivity of the thiol–maleimide conjugation in the presence of a disulfide linkage was established through 1H NMR spectroscopy and Ellman’s test. Rapid degradation of HGs in the presence of thiol-containing solution was evident from the reduction in storage modulus. HGs encapsulated with fluorescent dye-labeled dextran polymers and bovine serum albumin were fabricated, and their cargo release was investigated under passive and active conditions upon exposure to DTT. One can envision that the rapid gelation and fast on-demand dissolution under relatively benign conditions would make these polymeric materials attractive for a range of biomedical applications.

Carbon Quantum Dots-Based Fluorescent Hydrogel Hybrid Platform for Sensitive Detection of Iron Ions

In this study, we prepared novel fluorescent carbon quantum dots/hydrogel nanocomposite material (CQDsHG) with good adsorption and stable fluorescence detection of Fe3+. The materials were subsequently characterized according to their morphological features, chemical composition, adsorption, and optical properties. The carbon quantum dots (CQDs) were prepared using a microwave-assisted hydrothermal method in no more than 15 min, and the as-prepared CQDs exhibited excellent water solubility, as well as emitted strong bright blue fluorescence with an ultrahigh quantum yield of 93.60%. The CQDs were then loaded into a hydrogel (HG) using the sol-gel method to obtain a functional CQDsHG. The CQDsHG exhibited high adsorption amounts (31.94 mg/g) and a good quenching response for Fe3+, thus, it could be used as a sensor to selectively detect Fe3+ in the linear range of 0–150 μM with a detection limit of 0.24 μM. We observed minimal difference in the fluorescence lifetimes between the CQDsHG with and without a quencher (Fe3+), with values of 5.816 ns and 5.824 ns, respectively, confirming that Fe3+ was statically quenched on CQDsHG. The results indicated that the innovative combination of CQDs and HG can improve the synergistic performance of each component for the adsorption and quantitative detection of heavy metal ions in the aqueous environment.

A novel multifunctional Salecan/κ-carrageenan composite hydrogel with anti-freezing properties: Advanced rheology, thermal analysis and model fitting

The multifunctional hydrogels (HGs) have attracted intensive concern in biomedicine, food, and flexible devices. Nevertheless, chemically crosslinked synthetic HGs are commonly under specific restrictions because of their possible biotoxicity. This study focuses on the employment of physical approaches to prepare novel Salecan/κ-carrageenan composites HGs (CHGs) without changing their basic structures. Comprehensive rheological and thermal studies have been performed to investigate their distinctive properties. The data obtained from the tests and model fitting confirmed that the highest activation energy of CHGs was 172,142.2 J/mol, and the maximum equilibrium creep compliance was 0.0085 1/Pa. The sample recovery rate could reach 92.6%, while the anti-freezing temperature can be as low as −20 °C. It is the first report focusing on novel CHGs made from Salecan and κ-carrageenan with ideal anti-freezing ability, enhanced thermostability, good injectability, self-recovery, and other rheological properties that will provide effective support for various future applications.

Effects of PGPR Bioinoculants, Hydrogel and Biochar on Growth and Physiology of Soybean under Drought Stress

ABSTRACT The drought ameliorative effects of poly(acrylic acid) hydrogel (HG), biochar (BC) and plant growth-promoting rhizobacteria (PGPR) were evaluated on soybean exposed to drought stress. Prior to sowing, soybean seeds were soaked for 3–4 h in the broth culture of Planomicrobium chinense (MF616408) and Pseudomonas putida (KX574857), while BC (5 g/kg soil) and HG (2 g/kg soil) were mixed with autoclaved soil. Plants were well watered and grown under natural conditions for 35 d, followed by 4 d of drought exposure. While drought stress negatively impacted plant growth, effects of individual application of BC, HG and PGPR in combating the drought stress were noteworthy and a predominant increase in plant biomass by BC and plant antioxidant enzymes (superoxide dismutase (SOD) and catalase (CAT)) and elevated soil nutrients by PGPR were observed. PGPR assisted HG in retaining the soil moisture content (SMC) and further elevated the leaf relative water content (LRWC) and fresh weight (FW) root. The combined application of HG and PGPR consortium was most effective in improving photosynthetic pigments, FW shoot and soil fertility status. Likewise, the combined application of BC and PGPR had stimulatory effects on plant osmoregulants, with BC combined with Pseudomonas putida significantly improving soil nutrient retention. It is inferred that HG and BC in combination with PGPR isolates and PGPR consortium are effective drought mitigating strategies.

Evaluation of an Injectable Hydrogel Based on Hyaluronic Acid-Chitosan/β-Glycerophosphate-Loaded Mesenchymal Stem Cells in Enhancing the Therapeutic Efficacy of Myocardial Infarction.

Myocardial infarction (MI), which is due to cardiac dysfunction, results in morbidity and mortality. Moreover, the cellular activity of transplanted mesenchymal stem cells (MSCs) generally limits their therapeutic efficacy in the treatment of MI. Here, inject able hyaluronic acid-chitosan/β-glycerophosphate (HA-CS/β-GP) hydrogel-loaded MSCs are prepared, after which their effects on the treatment of MI are investigated. The synthesized HA-CS/β-GP hydrogels exhibit swelling ratio, an in vitro degradation value, and a gelatin time of 82.19 ± 4.1, 88.18% ± 2.4%, and 9 s, respectively. Further, rheological studies revealed that the elastic modulus of the HA-CS/β-GP hydrogels is ≥230 Pa, exhibiting large elastic to viscous modulus ratio, which indicates their mechanical strength. Furthermore, the in vitro 3T3 cell and MSC culture studies confirm the good biocompatibility of the HA-CS and HA-CS/β-GP hydrogels. The implantation of the synthesized hydrogels in the mouse MI model considerably improves the therapeutic effect of the MSCs (enhanced cardiac function, reduced cardiomyocyte apoptosis, and increased vascularization) for the first time. The innovative synergistic strategy of combining injectable HA-CS and HA-CS/β-GP hydro gels with MSCs may be suitable for the effective treatment of cardiac morbidity due to MIs.

Microwave-Assisted Synthesis of Modified Glycidyl Methacrylate-Ethyl Methacrylate Oligomers, Their Physico-Chemical and Biological Characteristics.

In this study, well-known oligomers containing ethyl methacrylate (EMA) and glycidyl methacrylate (GMA) components for the synthesis of the oligomeric network [P(EMA)-co-(GMA)] were used. In order to change the hydrophobic character of the [P(EMA)-co-(GMA)] to a more hydrophilic one, the oligomeric chain was functionalized with ethanolamine, xylitol (Xyl), and L-ornithine. The oligomeric materials were characterized by nuclear magnetic resonance and Fourier transform infrared spectroscopy, scanning electron microscopy, and differential thermogravimetric analysis. In the final stage, thanks to the large amount of -OH groups, it was possible to obtain a three-dimensional hydrogel (HG) network. The HGs were used as a matrix for the immobilization of methylene blue, which was chosen as a model compound of active substances, the release of which from the matrix was examined using spectrophotometric detection. The cytotoxic test was performed using fluid extracts of the HGs and human skin fibroblasts. The cell culture experiment showed that only [P(EMA)-co-(GMA)] and [P(EMA)-co-(GMA)]-Xyl have the potential to be used in biomedical applications. The studies revealed that the obtained HGs were porous and non-cytotoxic, which gives them the opportunity to possess great potential for use as an oligomeric network for drug reservoirs in in vitro application.

Abstract 14327: Intramyocardial Delivery of an Imageable Theranostic Hydrogel Post Myocardial Infarction Alters Regional Strain and Reduces Remodeling in Chronic Porcine Model

Introduction: Myocardial infarction (MI) causes acute regional changes in stiffness and strain, resulting in pathological remodeling in the left ventricle (LV). Intramyocardial injection of hydrogel (HG) into the MI region may alter deformation and improve LV remodeling. Using high resolution cineCT (CCT) we evaluated changes in regional strain, global function, and geometry in chronic porcine MI model. Methods: Yorkshire pigs (n=12) subjected to 90 min balloon occlusion and reperfusion were randomized 5 days post MI to intramyocardial delivery of MI+HG (n=6) or MI only (n=6). Imageable HG was delivered in a 3x3 grid after assessing MI region with hybrid 201 Tl SPECT/CT. Contrast CCT was performed at baseline, day 5 (post MI before HG delivery), and day 12 (7 days post HG delivery) to assess end diastolic volume (EDV) and ejection fraction (EF). Custom software was used to calculate 3D myocardial Lagrangian strains on 6 HG animals and 3 MI only animals in remote, border (>50% normal) and MI regions (<50% normal). Results: At day 5 in both groups, EDV increased by 13.2% (p=0.016), LVEF decreased by 15.7% (p=0.008), and radial strain (E rr ) decreased in MI region by -0.11 (p=0.007). On day 12, EDV decreased by 8.3% in the MI+HG group but increased by 10.4% in the MI only group (p=0.003). LVEF increased significantly in the MI+HG group by 8.96% and was significantly greater than in MI only group (p=0.027) which had no significant changes. Average change in E rr between baseline and day 12 was not different between groups within the MI (p=0.13) or border region (p=0.67). However, average E rr did not decline in the MI+HG group (+0.029) but significantly declined in MI only group (-0.14, p=0.017) (MI+HG vs MI only; p=0.003), mirroring EDV changes. Conclusions: Intramyocardial delivery of HG 5 days post-MI resulted in greater improvement in E rr in remote region and global LVEF and a decrease in EDV suggesting reduced LV remodeling compared to MI only controls.

DEXTRAN-CHITOSAN-nTIO2 TAILORED HYDROGELS (DEXCH-nTIO2-HGS) AS VERSATILE TOOL IN EXPLORING THE POTENTIAL OF KAEMPFEROL FOR EFFECTIVE DIABETIC WOUND HEALING

Grafts made from synthetic polymers perform poorly in wound healing applications. In these applications, dextranchitosan based materials can be produced and fabricated to present a novel scaffold for wound healing engineering. The aim of this study was to evaluate in-vitro the mechanical properties of a novel dextran-chitosan based hydrogel formulation to examine its potential for this scaffold. Kaempferol (KMF) (obtained from leaves of Ipomea carnea Jacq) loaded hydrogel (HGs) was prepared using dextran-chitosan (Dex-CH) and PEG as a cross linking agent with nano titanium dioxide (nTiO2). Subsequently Dex and CH solution were blended together to form a homogeneous DexCH binary blend mixture with the PEG as crosslinker and characterized for various paramters like AFM (Atomic Force Microscopy), mechanical (tensile) strength of hydrogel, swelling property, entrapment efficiency and drug release. The role of hydrogel was assessed by wound healing activity tested beside wound contraction, collagen content, dried granuloma weights and antioxidant property. Percent entrapment efficiency of optimized hydrogel found to be 89.36 ± 1.19%. KMF loaded DexCH- nTiO2-HGs were able to release 95.36%, KMF in 24 hrs. The level of superoxide dismutase (SOD) and catalase were found increased significantly in granuloma tissue of KMF treated group. The significant wound healing effect in normal wound tissues as well as diabetic with higher antioxidant activity founded in KMF-DexCH-nTiO2-HGs. Prepared hydrogel formulations (KMF loaded DexCH- nTiO2-HGs) were proved to be highly suitable on grounds of moist nature, biocompatibility, biodegradability and antioxidant effectiveness.

Transformation of Organic Waste Materials as H2O Gel and Its Influence on Growth of Maize (Zea mays L.)

ABSTRACT Water is an essential component for healthy plants and a limiting factor of global crop production. Recently, use of water absorbent compounds (nontoxic hydrocarbons) is rapidly increasing for optimum crop growth under water stress environment. These polymers absorb water and release it slowly as per crop requirement to mitigate water scarcity. This research study was carried out at College of Agriculture, University of Sargodha, Punjab, Pakistan, during year 2018. In this experiment, first, water absorbent gel was formulated from different organic wastes (waste activated sludge and rice husk) under controlled conditions (temperature 28 ± 2 °C and relative humidity 55 ± 5%) in the laboratory. Then, a pot experiment was conducted to evaluate its efficiency on maize. The experiment comprised three treatments (water gel at 0 (T1), 1.5% (T2) and 2.5% (T3) of total soil bulk mass, respectively, along with recommended nitrogen (N), phosphorus (P), and potassium (K) doses at 160, 80, and 60 kg ha−1, respectively, with 12 replications using completely randomized design. The crop was grown for 90 days after sowing. Exogenous application of water gel at 1.5% of total soil mass (150 g) along with recommended dose of NPK (T2) significantly (P ≤ 0.05) enhanced plant growth traits including plant height (120.58 cm), stem diameter (18.42 mm), shoot fresh (40.42 g), and dry biomass (21.25 g), root fresh (23.50 g), and dry biomass (6.75 g), and chlorophyll (8.65 mg g−1 leaf Fwt) and relative leaf water contents (75.10). The morphological parameters of maize were significantly affected by T2 with reference to T3 and control treatments. Yield and yield-related traits of maize were significantly enhanced at T2. It is plausible to conclude that these eco-friendly super absorbent polymers (water gel) are capable to minimize the water deficiency to a great extent. Abbreviations: Relative water content (RWC); Shoot fresh weight (SFW); Shoot dry weight (SDW); Root fresh weight (RFW); Root dry weight (RDW); Chlorophyll (Chl); Germination percentage (%); Control (CK); Nitrogen (N); Phosphorus (P); Potassium (K); Hydrogel (HG)

Mithramycin delivery systems to develop effective therapies in sarcomas

BackgroundSarcomas comprise a group of aggressive malignancies with very little treatment options beyond standard chemotherapy. Reposition of approved drugs represents an attractive approach to identify effective therapeutic compounds. One example is mithramycin (MTM), a natural antibiotic which has demonstrated a strong antitumour activity in several tumour types, including sarcomas. However, its widespread use in the clinic was limited by its poor toxicity profile.ResultsIn order to improve the therapeutic index of MTM, we have loaded MTM into newly developed nanocarrier formulations. First, polylactide (PLA) polymeric nanoparticles (NPs) were generated by nanoprecipitation. Also, liposomes (LIP) were prepared by ethanol injection and evaporation solvent method. Finally, MTM-loaded hydrogels (HG) were obtained by passive loading using a urea derivative non-peptidic hydrogelator. MTM-loaded NPs and LIP display optimal hydrodynamic radii between 80 and 105 nm with a very low polydispersity index (PdI) and encapsulation efficiencies (EE) of 92 and 30%, respectively. All formulations show a high stability and different release rates ranging from a fast release in HG (100% after 30 min) to more sustained release from NPs (100% after 24 h) and LIP (40% after 48 h). In vitro assays confirmed that all assayed MTM formulations retain the cytotoxic, anti-invasive and anti-stemness potential of free MTM in models of myxoid liposarcoma, undifferentiated pleomorphic sarcoma and chondrosarcoma. In addition, whole genome transcriptomic analysis evidenced the ability of MTM, both free and encapsulated, to act as a multi-repressor of several tumour-promoting pathways at once. Importantly, the treatment of mice bearing sarcoma xenografts showed that encapsulated MTM exhibited enhanced therapeutic effects and was better tolerated than free MTM.ConclusionsOverall, these novel formulations may represent an efficient and safer MTM-delivering alternative for sarcoma treatment.Graphical abstract

Brennstoffbetriebene und enzymregulierte redoxresponsive supramolekulare Hydrogele

AbstractIn Hydrogele eingebrachte chemische Reaktionsnetzwerke können responsive Materialien zu komplexen, selbstregulierenden Materialien transformieren, die eine Rückkopplung auf externe Stimuli generieren können. Diese Arbeit präsentiert Hydrogele aus dem Wirt‐Gast‐Paar β‐Cyclodextrin und Ferrocen als supramolekulare Vernetzer. Ein redoxresponsives Verhalten des Systems wird induziert durch die Treibstoff‐Enzym‐Paare Meerrettich‐Peroxidase/H2O2 und Glucose‐Oxidase (GOx)/d‐Glucose. Das Hydrogel kann durch Variation der Konzentration des Reduktionstreibstoffs d‐Glucose von einem responsiven zu einem selbstregulierenden supramolekularen System umgewandelt werden. Gestartet wird das selbstregulierende Verhalten durch die Bildung eines Oxidationsmittels innerhalb des Gels durch das Cofaktor‐Intermediat GOx[FADH2]. UV/Vis‐Spektroskopie, Rheologie und kinetische Modellierung wurden angewendet, um dieses Nichtgleichgewichtsverhalten und die Programmierbarkeit der Rückkopplung des Hydrogels, unter anderem die Anpassung des Speichermoduls und die mögliche Anwendung als Glucose‐Sensor, zu beleuchten.