Search Results (58)

The accumulation of dissolved species during the in situ leaching (ISL) of uranium can lead to ore-layer blockage and reduced production capacity. Clay minerals, including montmorillonite, chlorite, kaolinite, and illite, are the primary cementing and filling materials in sandstone-hosted uranium deposits in China. However, previous studies have predominantly focused on the leaching behavior of uranium minerals, while systematic investigations into the dissolution mechanism of clay minerals under CO₂+O₂ conditions remain scarce. In this study, laboratory dissolution experiments, scanning electron microscopy–energy-dispersive spectroscopy (SEM-EDS), computed tomography (CT) scanning, and field verification were conducted to systematically investigate the dissolution behavior of major clay minerals and their contribution to ore-layer blockage under CO₂+O₂ leaching conditions. The results indicate the following: (1) Montmorillonite exhibited the most significant dissolution, with granular deposits rich in Ca and Si formed on its surface, which were inferred to be Ca-Si-rich precipitates. (2) Obvious changes in both microstructure and macroscopic physical properties of clay minerals were observed before and after leaching, with porosity decreasing by approximately 12.96% and permeability decreasing by approximately 10.16%. (3) Field verification revealed that the scale in the ore layer, filter cloth blockage, and resin surface caking were primarily composed of silica gel and hydroxide/carbonate precipitates of Al, Ca, and Fe, which are closely related to the dissolution and leaching of clay minerals. This study confirms that montmorillonite is the main source of clogging substances, and long-term closed circulation of injection and extraction leads to the accumulation of precipitates, exerting a significant impact on the uranium-leaching system. The findings provide a theoretical basis for anti-clogging and permeability enhancement in CO₂+O₂ ISL operations. Full article

Objective: Conventional progesterone (P4) formulations suffer from low bioavailability, severe local irritation, and poor patient adherence due to P4’s poor aqueous solubility. This work aimed to develop and screen a biodegradable PLGA/NMP (Poly(lactic-co-glycolic acid)/N-methyl-2-pyrrolidone) injectable in situ gel for sustained P4 delivery to overcome these clinical limitations. Significance: Commercial oral, vaginal, and oil-based intramuscular P4 preparations cannot maintain stable long-term drug exposure, and they cause injection-site pain/inflammation. The screened in situ depot system reduces administration frequency and local tissue irritation, supporting convenient luteal phase support and pregnancy maintenance. Methods: Nine formulations with variable P4 loading (10–50% w/w) and PLGA concentration (15–55% w/w) were fabricated. Formulations were screened via three core endpoints: injectability (injection force and discharge rate), in vitro sustained release in 10% Hydroxypropyl-β-cyclodextrin (HP-β-CD)-Phosphate-buffered saline (PBS) sink medium, and 7-day subcutaneous histocompatibility in rats. high-performance liquid chromatography (HPLC) was validated for progesterone quantification; Hematoxylin and eosin (H&E) staining assessed local inflammatory responses. Results: Formulations with progesterone ≤ 30% w/w and PLGA ≤ 35% w/w exhibited acceptable injectability (injection force < 50 N; discharge rate > 79%). Higher PLGA concentrations suppressed initial burst release (16.74% at 8 h for 35% PLGA vs. 29.8% for 20% PLGA). All formulations formed stable ellipsoidal subcutaneous depots and completed progesterone release within 4 days. Histopathology revealed only mild local inflammation (histological score = 1) without severe necrosis, superior to highly irritating oil injections in formulation control groups. Conclusions: The screened PLGA-based progesterone in situ gel resolves critical drawbacks of traditional progesterone dosage forms. This low-irritation, sustained-release injectable platform provides a scalable industrial formulation candidate for long-acting hormone therapy. Full article

Controlling fibril generation and retaining their morphology during secondary thermal processing remain critical challenges for in-situ microfibrillar composites. Herein, we propose a “melt blending–hot drawing–low-temperature injection” cascade strategy to fabricate polypropylene/polyamide 66 (PP/PA66) composites. By decoupling the synergistic effects of draw ratio (λ) and compatibilizer (PP-g-MAH), an optimal fibrillation window was identified (15 wt% PA66, 3 wt% compatibilizer, λ = 9), which balances interfacial tension and viscous drag to form a dense, oriented microfibrillar network. This solid-state network accelerates matrix nucleation (though slightly restricting overall crystallinity) and induces gel-like rheological behavior through severe structural confinement. Crucially, we demonstrate that conventional high-temperature injection (265 °C) triggers Rayleigh instability, causing fibril break-up and mechanical degradation. Conversely, low-temperature injection (210 °C) successfully achieves the “geometric freezing” of the metastable fibril network. Consequently, the optimal composite exhibits maximized static strength (45.3 MPa) and a continuous, significant leap in notch impact toughness (10.16 kJ/m²). This work bridges the gap between flow-induced fibrillation and thermodynamic morphological retention, offering a robust physical mechanism for high-performance polyolefin composites. Full article

Hydrogel-enabled adoptive cell therapy (ACT) offers a localized and controllable strategy for improving cellular immunotherapy in solid tumors. Hydrogels can enhance cell retention and persistence, support immune cell function within the tumor microenvironment, and reduce systemic toxicity associated with broadly delivered immune stimulants. However, delivery of living immune cells imposes practical constraints on hydrogel selection, including cytocompatible encapsulation, minimal handling and injection stress, adequate transport of oxygen and soluble cues, and an appropriate balance between local retention and timely cell egress. This review summarizes natural, synthetic, and hybrid hydrogel platforms and compares physical/supramolecular assembly, covalent and enzymatic crosslinking, and photo-crosslinking. Injectable in situ-forming depots and shear-thinning/self-healing gels are highlighted for locoregional administration. Key design and reporting dimensions of hydrogels are linked to immune cell outcomes relevant to ACT. These properties include mechanics and viscoelasticity, porosity and mass transport, degradability and remodeling, bioadhesion and extracellular matrix (ECM) mimicry, and immunogenicity versus immune shielding. Finally, a cell-type-tailored framework is presented for chimeric antigen receptor T (CAR-T), T cell receptor-engineered T (TCR-T), and tumor-infiltrating lymphocyte (TIL) products, natural killer (NK) cells, and dendritic cells (DCs) or macrophage/monocyte-derived effectors. Distinct biological requirements are used to motivate corresponding material architectures and cue presentation strategies. The review also provides quantitative reporting guidance, identifies evidence gaps for γδ T cells, and discusses in vivo validation, combination ACT strategies, and translational handling constraints. Full article

This study aimed to develop a solvent removal-based in situ forming gel (ISG) loaded with salicylic acid (SAL) using myristic acid (MYR) as a matrix-forming agent. SAL-loaded MYR-based ISGs were prepared using N-methyl-2-pyrrolidone (NMP) or dimethyl sulfoxide (DMSO) as solvents and evaluated for physicochemical properties, matrix formation behavior, mechanical characteristics, and in vitro drug release. Increasing MYR content influenced viscosity, gel formation kinetics, and depot integrity, resulting in prolonged SAL release of up to 20 days in DMSO-based formulations. The release kinetics were best described by the Peppas–Sahlin model, indicating diffusion-dominated drug transport. The selected formulation containing 30% w/w SAL and 20% w/w MYR exhibited acceptable injectability, reproducible in situ matrix formation, and sustained drug retention. Antimicrobial testing confirmed that SAL retained biological activity against oral pathogens following incorporation into the ISG system, although solvent contributions to antimicrobial effects were also observed. These findings demonstrate the feasibility of a MYR-based ISG system in which SAL contributes to both therapeutic activity and matrix formation, supporting its potential for localized oral drug delivery. Full article

Biocompatible stimuli-sensitive hydrogels are a versatile and promising class of materials with significant potential for various biomedical applications. These ‘’smart’’ hydrogels can dynamically respond to external environmental stimuli such as pH, temperature, enzymes, or biomolecular interactions, enabling controlled drug release, tissue regeneration, wound healing, and biosensing applications. Hydrogels derived from natural polymers, including chitosan, alginate, collagen, and hyaluronic acid, offer key advantages such as intrinsic biocompatibility, biodegradability, and the ability to mimic the extracellular matrix. Their ability to respond to environmental stimuli—including pH, temperature, redox potential, and enzymatic activity—enables control over drug release and tissue regeneration processes. This review explores the fundamental principles governing the design, properties, and mechanisms of responsiveness of natural stimuli-sensitive hydrogels. It also highlights recent advancements in their biomedical applications, discusses existing challenges, and outlines future research directions aimed at improving their functional performance and therapeutic potential for sustainable healthcare solutions. Full article

Background/Objectives: Lidocaine hydrochloride (LD-HCl) is the most commonly used local anesthetic in dentistry, often administered with epinephrine to extend its duration and reduce systemic absorption. However, its relatively short duration of action, the need for repeated injections, and the unpleasant taste may limit patient compliance and procedural efficiency. This study aimed to develop and evaluate a novel injectable nanoemulsion-based in situ gel depot system of LD to provide prolonged anesthetic activity. Methods: LD-loaded nanoemulsions were formulated by high-shear homogenization followed by probe sonication, employing Miglyol 812 N (oil phase), a combination of Tween 80 and soy lecithin (surfactant–co-surfactant), glycerin, and deionized water (aqueous phase). The selected nanoemulsion (S1) was dispersed in a thermoreversible poloxamer solution to form a nanoemulgel. The preparation was evaluated for globule diameter and uniformity, zeta potential, surface morphology, pH, drug content, stability, rheological behavior, injectability, and in vitro drug release. Analgesic efficacy was assessed via tail-flick and thermal paw withdrawal latency tests in Wistar rats. Cardiovascular safety was monitored using non-invasive electrocardiography and blood pressure measurements. Results: The developed nanoemulsions demonstrated a spherical shape, nanometer size (206 nm), high zeta-potential (−66.67 mV) and uniform size distribution, with a polydispersity index of approximately 0.40, while the nanoemulgel demonstrated appropriate thixotropic properties for parenteral administration. In vitro release profiles showed steady LD release (5 h), following the Higuchi model. In vivo studies showed significantly prolonged analgesic effects lasting up to 150 min (2.5 h) compared to standard LD-HCl injection (p < 0.001), with no adverse cardiovascular effects observed. Conclusions: The developed injectable LD in situ nanoemulgel offers a promising, patient-friendly alternative for prolonged anesthetic delivery in dental and operative procedures, potentially reducing the need for repeated injections and enhancing procedural comfort. Full article

Tests during methane hydrate (MH) production in Japan have shown that excessive water production is a primary challenge in MH development. It can lead to sand production, inhibit effective reservoir depressurization, and hinder gas production. This study investigated the ability of a reactive grout, produced by the in situ reaction of CO₂ with sodium silicate (SS), to inhibit water generation from unconsolidated sand layers by forming a water-blocking gel barrier. The performance of this grout was evaluated through laboratory experiments using silica sand as a porous medium. Under controlled conditions, diluted SS and CO₂ were sequentially injected. The injection and gelation processes were monitored in real time using CT scanning, and SEM was employed to analyze the microstructure of the reaction products. The results indicated that SS exhibited piston-like flow, with elevated concentrations increasing viscosity and promoting more uniform injection. CO₂ injection resulted in successful in situ gel formation. A homogeneous gel distribution decreased permeability by ~98% when the SS concentration was 25 wt%. However, at 50 wt%, rapid localized gelation caused preferential flow paths and reduced sealing efficiency. These findings highlight the potential of CO₂ reactive grouting for water management in MH exploitation and the importance of optimizing injection parameters. Full article

Postoperative adhesions are a prevalent complication following abdominal surgeries, often leading to significant clinical challenges. This study introduces an innovative solution utilizing a polyethylene glycol (PEG)-based triblock copolymer to form an injectable, self-healing hydrogel aimed at preventing these adhesions. The hydrogel, formulated with temperature-responsive and self-healing properties through the incorporation of poly (N-isopropyl acrylamide) (PNIPAM) and anion–pi interactions, was synthesized using reversible addition–fragmentation chain transfer (RAFT) polymerization. The hydrogel’s physical properties, biocompatibility, hemostatic effect, and anti-adhesive capabilities were rigorously tested through in vitro and in vivo experiments involving rat models. It demonstrated excellent biocompatibility, effective tissue adhesion, and robust hemostatic properties. Most notably, it exhibited significant anti-adhesive effects in a rat abdominal wall–cecum model, reducing adhesion formation effectively compared to controls. The PEG-based injectable hydrogel presents a promising approach for postoperative adhesion prevention. Its ability to gel in situ triggered by body heat, coupled with its self-healing properties, provides a substantial advantage in clinical settings, indicating its potential utility as a novel anti-adhesion material. Full article

Cellulose acetate butyrate (CAB) and cellulose acetate propionate (CAP) are biobased materials that are insoluble in water and present a potential alternative to fossil-based plastics. Solvent removal-induced in situ matrices are gaining attention as an innovative dosage form for localized drug delivery for periodontitis therapy. This study aims to develop levofloxacin hemihydrate (Lh)-loaded in situ matrices formed through solvent removal, incorporating various molecular weights (MWs) and concentrations of CAB and CAP. Increased MWs and higher concentrations of these cellulosic esters significantly improved formulation viscosity and injection force, contributing to enhanced phase inversion and greater matrix toughness. Microscopic analysis of interfacial phase changes revealed progressive thickening of the matrix over time, which was influenced by polymer concentration and limited solvent movement. The transformed matrices with high MW CAP and elevated CAB content demonstrated prolonged drug release, predominantly following first-order kinetics, suggesting drug dissolution and diffusion through the scaffold structure. CAB-based in situ matrices containing 15% and 20% polymer exhibited low viscosities suitable for injection, along with optimal gel formation for maintaining their shape, and adhered effectively to periodontal pockets. These matrices provided extended Lh release for up to 120 h and inhibited the growth of periodontopathic bacteria for over 15 days. Therefore, the developed Lh-loaded in situ matrices show promise as an effective treatment for periodontitis, warranting further research to explore their therapeutic potential. Full article

Long-acting injectable (LAI) formulations have revolutionized veterinary pharmaceuticals by improving patient compliance, minimizing dosage frequency, and improving therapeutic efficacy. These formulations utilize advanced drug delivery technologies, including microspheres, liposomes, oil solutions/suspensions, in situ-forming gels, and implants to achieve extended drug release. Biodegradable polymers such as poly(lactic-co-glycolic acid) (PLGA), and polycaprolactone (PCL) have been approved by the USFDA and are widely employed in the development of various LAIs, offering controlled drug release and minimizing the side effects. Various classes of veterinary medicines, including non-steroidal anti-inflammatory drugs (NSAIDs), antibiotics, and reproductive hormones, have been successfully formulated as LAIs. Some remarkable LAI products, such as ProHeart^® (moxidectin), Excede^® (ceftiofur), and POSILACTM (recombinant bovine somatotropin), show clinical relevance and commercial success. This review provides comprehensive information on the formulation strategies currently being used and the emerging technologies in LAIs for veterinary purposes. Additionally, challenges in characterization, in vitro testing, in vitro in vivo correlation (IVIVC), and safety concerns regarding biocompatibility are discussed, along with the prospects for next-generation LAIs. Continued advancement in the field of LAI in veterinary medicine is essential for improving animal health. Full article

Foam and hydrogel profile control are commonly utilized water-blocking and profile modification techniques in oil fields. This study integrates a foam system with a gel system, employing an organic titanium crosslinking agent to crosslink polyvinyl alcohol, thereby forming a gel system. Concurrently, a gas-evolving agent is incorporated into the system to induce in situ foaming, thereby creating an environmentally benign foam gel system. The fundamental constituents of this system comprise 2 wt% to 5 wt% polyvinyl alcohol, 2 wt% to 4 wt% crosslinker, and 0.3 wt% to 0.9 wt% gas-generating agent. By varying the amounts of each component, the strength grade, gelation time, and foaming volume of the foam gel can be effectively adjusted. The results of the temperature resistance performance evaluation indicate that within the temperature range of 80 °C to 130 °C, the gelation performance of the foam gel is stable and good. At 90 °C, the foam gel can remain stable for 340 days with minimal strength variation. The plugging experiments indicate that the formulated foam gel system exhibits superior injectability and can effectively seal the sand-filled tube model, achieving a blocking efficiency of up to 96.36%. Full article

Cellulose acetate butyrate is a biodegradable cellulose ester bioplastic produced from plentiful natural plant-based resources. Solvent-exchange-induced in situ gels are particularly promising for periodontitis therapy, as this dosage form allows for the direct delivery of high concentrations of antimicrobial agents to the localized periodontal pocket. This study developed an in situ gel for periodontitis treatment, incorporating a combination of metronidazole and doxycycline hyclate, with cellulose acetate butyrate serving as the matrix-forming agent. Consequently, assessments were conducted on the physicochemical properties, gel formation, drug permeation, drug release, morphological topography, and antimicrobial activities of the formulation. The formulation demonstrated an increased slope characteristic of Newtonian flow at higher bioplastic concentrations. The adequate polymer concentration facilitated swift phase inversion, resulting in robust, solid-like matrices. The mechanical characteristics of the transformed in situ gel typically exhibit an upward trend as the polymer concentration increased. The utilization of sodium fluorescein and Nile red as fluorescent probes effectively tracked the interfacial solvent–aqueous movement during the phase inversion of in situ gels, confirming that the cellulose acetate butyrate matrix delayed the solvent exchange process. The initial burst release of metronidazole and doxycycline hyclate was minimized, achieving a sustained release profile over 7 days in in situ gels containing 25% and 40% cellulose acetate butyrate, primarily governed by a diffusion-controlled release mechanism. Metronidazole showed higher permeation through the porcine buccal membrane, while doxycycline hyclate exhibited greater tissue accumulation, both influenced by polymer concentration. The more highly concentrated polymeric in situ gel formed a uniformly porous structure. Metronidazole and doxycycline hyclate-loaded in situ gels showed synergistic antibacterial effects against S. aureus and P. gingivalis. Over time, the more highly concentrated polymeric in situ gel showed superior retention of antibacterial efficacy due to its denser cellulose acetate butyrate matrix, which modulated drug release and enhanced synergistic effects, making it a promising injectable treatment for periodontitis, particularly against P. gingivalis. Full article

Injectable, in situ-forming hydrogels, both biocompatible and biodegradable, have garnered significant attention in tissue engineering due to their potential for creating adaptable scaffolds. The adaptability of these hydrogels, made from natural proteins and polysaccharides, opens up a world of possibilities. In this study, sodium alginate was used to synthesize alginate di-aldehyde (ADA) through periodate oxidation, resulting in a lower molecular weight and reduced viscosity, with different degrees of oxidation (54% and 70%). The dual-crosslinking mechanism produced an injectable in situ hydrogel. Initially, physical crosslinking occurred between ADA and borax via borax complexation, followed by chemical crosslinking with gelatin through a Schiff’s base reaction, which takes place between the amino groups of gelatin and the aldehyde groups of ADA, without requiring an external crosslinking agent. The formation of Schiff’s base was confirmed by Fourier-transform infrared (FT-IR) spectroscopy. At the same time, the aldehyde groups in ADA were characterized using FT-IR, proton nuclear magnetic resonance (¹H NMR), and gel permeation chromatography (GPC), which determined its molecular weight. Furthermore, borax complexation was validated through boron-11 nuclear magnetic resonance (¹¹B NMR). The hydrogel formulation containing 70% ADA, polyethylene glycol (PEG), and 9% gelatin exhibited a decreased gelation time at physiological temperature, attributed to the increased gelatin content and higher degree of oxidation. Rheological analysis mirrored these findings, showing a correlation with gelation time. The swelling capacity was also enhanced due to the increased oxidation degree of PEG and the system’s elevated gelatin content and hydrophilicity. The hydrogel demonstrated an average pore size of 40–60 µm and a compressive strength of 376.80 kPa. The lower molecular weight and varied pH conditions influenced its degradation behavior. Notably, the hydrogel’s syringeability was deemed sufficient for practical applications, further enhancing its potential in tissue engineering. Given these properties, the 70% ADA/gelatin/PEG hydrogel is a promising candidate and a potential game-changer for injectable, self-crosslinking applications in tissue engineering. Its potential to revolutionize the field is inspiring and should motivate further exploration. Full article

Implantable drug delivery systems formed upon injection offer a host of advantages, including localized drug administration, sustained release, minimized side effects, and enhanced patient compliance. Among the various techniques utilized for the development of in situ forming drug implants, solvent-induced phase inversion emerges as a particularly promising approach. However, synthetic polymer-based implants have been associated with undesirable effects arising from polymer degradation. In response to this challenge, a novel category of drug delivery systems, known as phospholipids-based phase separation gels (PPSGs), has emerged. These gels, characterized by their low initial viscosity, exhibit injectability and undergo rapid transformation into in situ implants when exposed to an aqueous environment. A typical PPSG formulation comprises biodegradable components, such as phospholipids, pharmaceutical oil, and a minimal amount of ethanol. The minimized organic solvents in the composition show good biocompatibility. And the relatively simple composition holds promise for industrial-scale manufacturing. This comprehensive review provides an overview of the principles and advancements in PPSG systems, with specific emphasis on their suitability as drug delivery systems for a wide range of active pharmaceutical ingredients (APIs), spanning from small molecules to peptides and proteins. Additionally, we explore the critical parameters and underlying principles governing the formulation of PPSG-based drug delivery strategies, offering valuable insights on optimization strategies. Full article