ABSTRACT
INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), approved by the US FDA for obesity treatment, are typically administered subcutaneously, an invasive method leading to suboptimal patient adherence and peripheral side effects. Additionally, this route requires the drug to cross the restrictive blood-brain barrier (BBB), limiting its safety and effectiveness in weight management and cognitive addiction disorders. Delivering the drug intranasally could overcome these drawbacks. AREAS COVERED: This review summarizes GLP-1 RAs used as anti-obesity agents, focusing on the intranasal route as a potential pathway to deliver these biomolecules to the brain. It also discusses strategies to overcome challenges associated with nasal delivery. EXPERT OPINION: Nose-to-brain (N2B) pathways can address limitations of the subcutaneous route for GLP-1 RAs. However, peptide delivery to the brain is challenging due to nasal physiological barriers and the drug's physicochemical properties. Innovative approaches, such as cell permeation enhancers, mucoadhesive systems, and nanocarriers in nasal formulations, along with efficient drug delivery devices, show promising preclinical results. Despite this, successful preclinical data does not guarantee clinical effectiveness, highlighting the need for comprehensive clinical investigations to optimize formulations and fully utilize the nose-to-brain interface for peptide delivery.
Subject(s)
Administration, Intranasal , Anti-Obesity Agents , Blood-Brain Barrier , Brain , Drug Delivery Systems , Glucagon-Like Peptide 1 , Glucagon-Like Peptide-1 Receptor , Obesity , Humans , Obesity/drug therapy , Animals , Blood-Brain Barrier/metabolism , Glucagon-Like Peptide 1/administration & dosage , Brain/metabolism , Brain/drug effects , Anti-Obesity Agents/administration & dosage , Anti-Obesity Agents/therapeutic use , Anti-Obesity Agents/pharmacokinetics , Anti-Obesity Agents/pharmacology , Glucagon-Like Peptide-1 Receptor/agonistsABSTRACT
Chemiresistive polymer-based sensors are promising platforms for monitoring various gases and volatile organic compounds. While they offer appealing attributes, such as ease of fabrication, flexibility, and cost-effectiveness, most of these sensors have a nearly identical response to cross-reactive gases, such as ammonia (NH3) and carbon dioxide (CO2). Aiming to address the shortcomings of chemiresistive polymer-based sensors in selectivity and simultaneous measurements of cross-reactive gases, a chemiresistive sensor array was developed consisting of components sensitive to carbon dioxide and ammonia as well as a control segment to provide the baseline. The designed system demonstrated a wide detection range for both ammonia (ranging from 0.05 to 1000 ppm) and carbon dioxide (ranging from 103 to 106 ppm) at both room and low temperatures (e.g., 4 °C). Our results also demonstrate the ability of this sensor array for the simultaneous detection of carbon dioxide and ammonia selectively in the presence of other gases and volatile organic compounds. Finally, the array was used to monitor CO2/NH3 in real food samples to demonstrate the potential for real-world applications.
Subject(s)
Ammonia , Carbon Dioxide , Ammonia/analysis , Carbon Dioxide/analysis , Gases/analysis , Gases/chemistryABSTRACT
Carbon dioxide (CO2) gas sensing and monitoring have gained prominence for applications such as smart food packaging, environmental monitoring of greenhouse gases, and medical diagnostic tests. Although CO2 sensors based on metal oxide semiconductors are readily available, they often suffer from limitations such as high operating temperatures (>250 °C), limited response at elevated humidity levels (>60% RH), bulkiness, and limited selectivity. In this study, we designed a chemiresistive sensor for CO2 detection to overcome these problems. The sensing material of this sensor consists of a CO2 switchable polymer based on N-3-(dimethylamino)propyl methacrylamide (DMAPMAm) and methoxyethyl methacrylate (MEMA) [P(D-co-M)], and diethylamine. The designed sensor has a detection range for CO2 between 103 and 106 ppm even at high humidity levels (>80% RH), and it is capable of differentiating ammonia at low concentrations (0.1-5 ppm) from CO2. The addition of diethylamine improved sensor performance such as selectivity, response/recovery time, and long-term stability. These data demonstrate the potential of using this sensor for the detection of food spoilage.
Subject(s)
Carbon Dioxide , Carbon Dioxide/analysis , Humidity , Acrylamides/chemistry , Polymers/chemistry , Methacrylates/chemistry , Gases/analysisABSTRACT
Injectable hydrogels can support the body's innate healing capability by providing a temporary matrix for host cell ingrowth and neovascularization. The clinical adoption of current injectable systems remains low due to their cumbersome preparation requirements, device malfunction, product dislodgment during administration, and uncontrolled biological responses at the treatment site. To address these challenges, a fully synthetic and ready-to-use injectable biomaterial is engineered that forms an adhesive hydrogel that remains at the administration site regardless of defect anatomy. The product elicits a negligible local inflammatory response and fully resorbs into nontoxic components with minimal impact on internal organs. Preclinical animal studies confirm that the engineered hydrogel upregulates the regeneration of both soft and hard tissues by providing a temporary matrix to support host cell ingrowth and neovascularization. In a pilot clinical trial, the engineered hydrogel is successfully administered to a socket site post tooth extraction and forms adhesive hydrogel that stabilizes blood clot and supports soft and hard tissue regeneration. Accordingly, this injectable hydrogel exhibits high therapeutic potential and can be adopted to address multiple unmet needs in different clinical settings.
Subject(s)
Hydrogels , Hydrogels/pharmacologyABSTRACT
Native arteries contain a distinctive intima-media composed of organized elastin and an adventitia containing mature collagen fibrils. In contrast, implanted biodegradable small-diameter vascular grafts do not present spatially regenerated, organized elastin. The elastin-containing structures within the intima-media region encompass the elastic lamellae (EL) and internal elastic lamina (IEL) and are crucial for normal arterial function. Here, the development of a novel electrospun small-diameter vascular graft that facilitates de novo formation of a structurally appropriate elastin-containing intima-media region following implantation is described. The graft comprises a non-porous microstructure characterized by tropoelastin fibers that are embedded in a PGS matrix. After implantation in mouse abdominal aorta, the graft develops distinct cell and extracellular matrix profiles that approximate the native adventitia and intima-media by 8 weeks. Within the newly formed intima-media region there are circumferentially aligned smooth muscle cell layers that alternate with multiple EL similar to that found in the arterial wall. By 8 months, the developed adventitia region contains mature collagen fibrils and the neoartery presents a distinct IEL with thickness comparable to that in mouse abdominal aorta. It is proposed that this new class of material can generate the critically required, organized elastin needed for arterial regeneration.
Subject(s)
Blood Vessel Prosthesis , Elastin , Mice , Animals , Myocytes, Smooth Muscle , Arteries , CollagenABSTRACT
Amine-functionalized polymers (AFPs) are able to react with carbon dioxide (CO2) and are therefore useful in CO2 capture and sensing. To develop AFP-based CO2 sensors, it is critical to examine their electrical responses to CO2 over long periods of time, so that the device can be used consistently for measuring CO2 concentration. To this end, we synthesized poly(N-[3-(dimethylamino)propyl] methacrylamide) (pDMAPMAm) by free radical polymerization and tested its ability to behave as a CO2-responsive polymer in a transducer. The electrical response of this polymer to CO2 upon long exposure times was measured in both the aqueous and solid phases. Direct current resistance measurement tests on pDMAPMAm films printed along with the silver electrodes in the presence of CO2 at various concentrations reveal a two-region electrical response. Upon continuous exposure to different CO2 flow rates (at a constant pressure of 0.2 MPa), the resistance first decreased over time, reaching a minimum, followed by a gradual increase with further exposure to CO2. A similar trend is observed when CO2 is introduced to an aqueous solution of pDMAPMAm. The in situ monitoring of pH suggests that the change in resistance of pDMAPMAm can be attributed to the protonation of tertiary amine groups in the presence of CO2. This two-region response of pDMAPMAm is based on a proton-hopping mechanism and a change in the number of free amines when pDMAPMAm is exposed to various levels of CO2.
ABSTRACT
Hydrogen peroxide (H2O2) is a common chemical used in many industries and can be found in various biological environments, water, and air. Yet, H2O2 in a certain range of concentrations can be hazardous and toxic. Therefore, it is crucial to determine its concentration at different conditions for safety and diagnostic purposes. This review provides an insight about different types of sensors that have been developed for detection of H2O2. Their flexibility, stability, cost, detection limit, manufacturing, and challenges in their applications have been compared. More specifically the advantages and disadvantages of various flexible substrates that have been utilized for the design of H2O2 sensors were discussed. These substrates include carbonaceous substrates (e.g., reduced graphene oxide films, carbon cloth, carbon, and graphene fibers), polymeric substrates, paper, thin glass, and silicon wafers. Many of these substrates are often decorated with nanostructures composed of Pt, Au, Ag, MnO2, Fe3O4, or a conductive polymer to enhance the performance of sensors. The impact of these nanostructures on the sensing performance of resulting flexible H2O2 sensors has been reviewed in detail. In summary, the detection limits of these sensors are within the range of 100 nM-1 mM, which makes them potentially, but not necessarily, suitable for applications in health, food, and environmental monitoring. However, the required sample volume, cost, ease of manufacturing, and stability are often neglected compared to other detection parameters, which hinders sensors' real-world application. Future perspectives on how to address some of the substrate limitations and examples of application-driven sensors are also discussed.
ABSTRACT
Ethylene is a hormone that plays a critical role in many phases of plant growth and fruit ripening. Currently, detection of ethylene heavily relies on sophisticated and time-consuming conventional assays such as chromatography, spectroscopy, and electrochemical methods. Herein, we develop a polydiacetylene-based sensor for the detection of ethylene via color change. The sensors are prepared through the reaction between polydiacetylene and Lawesson's reagent that results in decorating polydiacetylene with terminal thiol groups. Upon exposure to ethylene, the sensor changes color from blue to red which is visible to the naked eye. Our device shows a limit of detection for ethylene at 600 ppm in air and can be applied for monitoring ethylene released during the fruit-ripening process. Such easy-to-use ethylene sensors may find applications in plant biology, agriculture, and food industry.
Subject(s)
Colorimetry , Sulfhydryl Compounds , Ethylenes , Polyacetylene PolymerABSTRACT
Injectable and phase-transitioning carriers from natural polysaccharides have great potential for the minimally invasive delivery of therapeutic proteins in the field of bone tissue engineering. In this study, a novel and highly viscous drug carrier was synthesized by a sequential process of deoxyribose polycondensation and esterification. The effect of synthesis parameters on the molecular weight, viscosity, and adhesion of the material was studied and correlated to temperature and time of polycondensation ( Tp and tp), time and temperature of esterification ( Te and te), and the molar ratio of the monomer ( R). The formulations were evaluated for molecular weight and distribution properties using GPC, chemical structures by FTIR and NMR spectra, and rheological properties using a rheometer. Formulations illustrated a wide range of viscosities (0.736 to 2225 Pa s), adhesion (0.896 to 58.45 N), and molecular weights (637 to 4216 Da), where viscosity was significantly reduced in the presence of low amounts of solvents (10-20%). The sustained release of BSA was observed over 42 days in vitro. The biocompatibility of poly(deoxyribose) isobutyrate (PDIB) as well as its potential as a bone morphogenetic protein delivery system was assessed in vivo using a rat ectopic bone model, where bone nodules were observed at 2 weeks. In summary, PDIB is a promising molecule with multiple applications for protein delivery, including for bone tissue engineering.
Subject(s)
Biocompatible Materials/pharmacology , Bone Morphogenetic Protein 2/pharmacology , Drug Delivery Systems , Tissue Engineering , Biocompatible Materials/chemistry , Bone Morphogenetic Protein 2/chemistry , Deoxyribose/chemistry , Drug Carriers/chemistry , Drug Carriers/pharmacology , Humans , Isobutyrates/chemistry , Rheology , Viscosity/drug effectsABSTRACT
Novel hydrogels with tunable mechanical properties similar to human soft tissue have increasing applications in biomedicine, soft robotics, and biocompatible electronics. However, most of these materials require multiple-step fabrication, are not robust, and compromise bioactivity. Thus, aiming to address these shortfalls, herein, we report a versatile hydrogel system with tunable properties and a facile one-pot fabrication process. The hydrogel system is comprised of a hydrogen-bonded hydrophilic polyurethane (HPU) network and a loosely crosslinked copolymer crosslinked with long chain crosslinkers and decorated with succinimide groups. The active succinimide sites conjugate to proteins, such as bovine serum albumin as a model protein, providing additional biocompatibility and controlled release of growth factors and peptides. The interpenetrating nature of this hydrogel system provides a high degree of freedom over mechanical and physical properties by adjusting the ratio of networks and the composition of the second network. Through this process, a library of biocompatible hydrogels with stiffness ranging from 1 to more than 200 kPa was developed. Moreover, it was found that the succinimide groups impact the degree of crosslinking and contribute to the controlled release of peptides.
Subject(s)
Hydrogels/chemistry , Peptides/chemistry , Animals , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Cattle , Cell Cycle Checkpoints/drug effects , Cell Line , Cell Survival/drug effects , Elastic Modulus , Human Umbilical Vein Endothelial Cells , Humans , Hydrophobic and Hydrophilic Interactions , Polyurethanes/chemistry , Serum Albumin, Bovine/chemistry , Serum Albumin, Bovine/metabolismABSTRACT
Lignin is a low-cost, natural polymer with abundant polar sites on its backbone that can be utilized for physical cross-linking of polymers. Here, we use lignin for additional cross-linking of hydrophilic polyether-based polyurethane (HPU) hydrogels, aiming to improve their mechanical properties and processability. Without reducing the swelling, simple addition of 2.5 wt % lignin increases the fracture energy and Young's modulus of HPU hydrogels from, respectively, 1540 ± 40 to 2050 ± 50 J m-2 and 1.29 ± 0.06 to 2.62 ± 0.84 MPa. Lignin also increases the lap shear adhesiveness of hydrogels and induces an immediate load recovery of 95%. We further confirm that hydrogen bonding is the dominant toughening mechanism and elucidate the toughening mechanism by applying the Lake-Thomas and a recently developed sequential debonding theory. We show that unlike the Lake-Thomas theory, the latter model is able to capture the impact of lignin on toughening of hydrogels. Moreover, the lignin-loaded HPU hydrogels are easily processable by various techniques, such as fiber spinning, casting, and 3D printing and are biocompatible with primary human dermal fibroblasts.
ABSTRACT
The spent liquor (SL) of neutral sulfite semi-chemical (NSSC) pulping process contains about 8 wt% lignocelluloses that can be extracted and used in the production of value-added materials. In this work, a flocculation process followed by centrifugation was considered for isolating lignosulfonate and hemicelluloses from SL. It was observed that, by adding 20 mg/g of polydiallyldimethylammuniom chloride (PDADMAC) with 100,000-200,000 g/mol molecular weight to SL, 45% of lignosulfonate and 39% of hemicelluloses were removed at 30°C. The lignocellulose removal was more efficient for the dual flocculation system of low and high molecular weights PDADMAC than for individual PDADMAC systems. Overall, 49% of lignosulfonate, 47% of hemicelluloses and 97% of turbidity were removed from SL from the dual system when 10 mg/g low molecular weight PDADMAC and 10 mg/g high molecular weight PDADMAC were added to the SL at 30°C, subsequently. The thermogravimetric analysis (TGA) of generated flocs showed that all samples had similar thermal behaviour and 13-16 wt% of flocs remained as ash after burning at 700°C in nitrogen. As the flocs are made of lignocellulosic materials and they are thermally stable, they could be used as fillers in paper board production. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:686-691, 2016.
Subject(s)
Centrifugation , Lignin/analogs & derivatives , Polyethylenes/chemistry , Quaternary Ammonium Compounds/chemistry , Sulfites/chemistry , Flocculation , Lignin/chemistry , Lignin/isolation & purificationABSTRACT
In this work, the adsorption of lignocelluloses from spent liquor (SL) of neutral sulfite semi chemical (NSSC) pulping process on bentonite was investigated. It was observed that 0.26g/g of lignin and 0.27g/g of hemicelluloses from SL were adsorbed on bentonite under the conditions of 50°C, 100rpm and 40g/gSL/bentonite after 3h of treatment. The adsorptions of lignin and hemicellulose were increased to 1.8g/g and 0.45g/g, respectively, via adding 15mg/g of polydiallyldimethylammonium chloride (PDADMAC) in the system of SL/bentonite. The turbidity and COD removals were improved from 69% to 93% and from 25% to 38% by adding PDADMAC to the SL/bentonite system, respectively. The increase in the heating value of bentonite (from 0 to 15.4MJ/kg) confirmed the adsorption of lignocelluloses. The modified bentonite can be used as filler in corrugated medium paper production or as fuel.
Subject(s)
Bentonite/chemistry , Biotechnology/methods , Lignin/chemistry , Sulfites/chemistry , Waste Disposal, Fluid , Adsorption , Biological Oxygen Demand Analysis , Kinetics , Molecular Weight , Nephelometry and Turbidimetry , Polyethylenes/chemistry , Polysaccharides/chemistry , Quaternary Ammonium Compounds/chemistry , Temperature , Thermogravimetry , Time FactorsABSTRACT
Wood chips are pretreated with steam prior to refining in the thermomechanical pulping process. The steam treatment dissolves part of lignin of wood chips in the spent liquor (SL) of this process, and subsequently the SL is sent to the wastewater system of the process. However, the lignin of SL can be used in the production of value-added chemicals, but it should first be separated from the SL in order to have a feasible downstream process. In this study, activated carbon (AC) was considered as an adsorbent to isolate lignin from SL. The results showed that the maximum adsorption of lignin on AC was 166 mg/g under the optimal conditions of pH 5.2, 30 degrees C and 3 h treatment. Furthermore, the separation of lignin from SL was improved from 45% to 60% by having a two-stage adsorption process at pH 5.2, which also reduced the turbidity and chemical oxygen demand of SL by 39% and 32%, respectively.
Subject(s)
Lignin/isolation & purification , Waste Disposal, Fluid/methods , Adsorption , Biological Oxygen Demand Analysis , Charcoal/chemistry , Industrial Waste , Lignin/chemistry , Wastewater/chemistryABSTRACT
Presently, the spent liquor (SL) of neutral sulfite semi chemical (NSSC) pulping process is treated in the waste water system. In this work, a new process for isolating lignocelluloses from the SL of an NSSC process is proposed and the effectiveness of this process is evaluated on industrially produced SL. The results showed that under the optimal conditions of pH 6, 30°C and 15mg/g poly ethylene imine (PEI) concentration in the SL, a maximum of 37% lignin and 37% hemicelluloses could be removed from SL. Alternatively, the dual system of poly diallyldimethyl ammonium chloride (PDADMAC) and PEI (7.5mg/g each) was evaluated in removing lignocelluloses from the SL; and the results showed that lignin and hemicellulose removals were improved to 47% and 50%, respectively. The turbidity and chemical oxygen demand (COD) of SL, as well as the elemental analysis of generated flocs were also assessed in this work.