Specific Release Research Articles

Experimental Study on the Inhibition Effect of the Inhibitor on Coal Spontaneous Combustion Under Critical Temperature.

At present, related research on inhibitors has been gradually improved, but there is still a lack of research on the inhibition characteristics at specific release temperatures and the mechanism of inhibiting coal spontaneous combustion. Based on this, In this study, the inhibition characteristics of adding inhibitor to coal under critical temperature (R70) are studied in depth. In the experiment, lignite was selected as the research object, and four different types of inhibitors, MgCl2, triphenyl phosphite (TPPI), Phytic acid (PA), and melatonin, were applied to coal samples at room temperature and 70 °C, respectively. The temperature-programmed-gas chromatography test and Fourier infrared spectroscopy experiment were carried out, and the oxidation kinetic parameters were calculated to study the oxidation characteristics and micromechanism of the coal samples in the process of spontaneous combustion. The experimental results show that the amount of CO gas release and oxygen consumption rate are lower, and the inhibition rate and apparent activation energy are higher when the inhibitor is added under R70 than at room temperature. Under R70, the content of oxygen-containing functional group -COOH with higher activity of inhibitor is reduced, the generation of active sites is inhibited, the concentration of active center is reduced, the path of mutual transformation between active sites and oxygen-containing functional groups is blocked, and the active groups are promoted to form a relatively stable inert oxygen-containing ether bond, which reduces the spontaneous combustion tendency of coal.

The state-of-art polyurethane nanoparticles for drug delivery applications.

Nowadays, polyurethanes (PUs) stand out as a promising option for drug delivery owing to their versatile properties. PUs have garnered significant attention in the biomedical sector and are extensively employed in diverse forms, including bulk devices, coatings, particles, and micelles. PUs are crucial in delivering various therapeutic agents such as antibiotics, anti-cancer medications, dermal treatments, and intravaginal rings. Effective drug release management is essential to ensure the intended therapeutic impact of PUs. Commercially available PU-based drug delivery products exemplify the adaptability of PUs in drug delivery, enabling researchers to tailor the polymer properties for specific drug release patterns. This review primarily focuses on the preparation of PU nanoparticles and their physiochemical properties for drug delivery applications, emphasizing how the formation of PUs affects the efficiency of drug delivery systems. Additionally, cutting-edge applications in drug delivery using PU nanoparticle systems, micelles, targeted, activatable, and fluorescence imaging-guided drug delivery applications are explored. Finally, the role of artificial intelligence and machine learning in drug design and delivery is discussed. The review concludes by addressing the challenges and providing perspectives on the future of PUs in drug delivery, aiming to inspire the design of more innovative solutions in this field.

DNA Cryogels with Anisotropic Mechanical and Responsive Properties for Specific Cell Capture and Release.

Due to their programmable stimuli-responsiveness, excellent biocompatibility, and water-rich and soft structures similar to biological tissues, smart DNA hydrogels hold great promise for biosensing and biomedical applications. However, most DNA hydrogels developed to date are composed of randomly oriented and isotropic polymer networks, and the resulting slow response to biotargets and lack of anisotropic properties similar to those of biological tissues have limited their extensive applications. Herein, anisotropic DNA hydrogels consisting of unidirectional void channels internally oriented up to macroscopic length scales were constructed by a directional cryopolymerization method, as exemplified by a DNA-incorporated covalently cross-linked DNA cryogel and a DNA duplex structure noncovalently cross-linked DNA cryogel. Results showed that the formation of unidirectional channels significantly improved the responsiveness of the gel matrix to biomacromolecular substances and further endowed the DNA cryogels with anisotropic properties, including anisotropic mechanical properties, anisotropic swelling/shrinking behaviors, and anisotropic responsiveness to specific biotargets. Moreover, the abundant oriented and long macroporous channels in the gel matrix facilitated the migration of cells, and through the introduction of aptamer structures and thermosensitive polymers, an anisotropic DNA cryogel-based platform was further constructed to achieve the highly efficient capture and release of specific cells. These anisotropic DNA hydrogels may provide new opportunities for the development of anisotropic separation and biosensing systems.

Modular design of cyclic peptide – polymer conjugate nanotubes for delivery and tunable release of anti-cancer drug compounds

High aspect-ratio nanomaterials have recently emerged as promising drug delivery vehicles due to evidence of strong cellular association and prolonged in vivo circulation times. Cyclic peptide - polymer conjugate nanotubes are excellent candidates due to their elongated morphology, their supramolecular composition and high degree of pliability due to the versatility in manipulating amino acid sequence and polymer type. In this work, we explore the use of a nanotube structure on which a potent anti-cancer drug, camptothecin, is attached alongside hydrophilic or amphiphilic RAFT polymers, which shield the cargo. We show that subtle modifications to the cleavable linker type and polymer architecture have a dramatic influence over the rate of drug release in biological conditions. In vitro studies revealed that multiple cancer cell lines in 2D and 3D models responded effectively to the nanotube treatment, and analogous fluorescently labelled materials revealed key mechanistic information regarding the degree of cellular uptake and intracellular fate. Importantly, the ability to instruct specific drug release profiles indicates a potential for these nanomaterials as vectors which can provide sustained drug concentrations for a maximal therapeutic effect.

Metformin‐Mediated Immunosuppressive Microenvironment Remodeling in Combination with Chemotherapy via a Spatial‐Specific Multi‐Responsive Carrier‐Free Self‐Assembled Nanoparticle

AbstractThe complex tumor immune pathology requires a precise spatial‐control release of the combination drugs, but most multi‐drug loaded nanoparticles release all drugs simultaneously in the tumor microenvironment (TME), making them difficult to reach the exact action site. To address the spatial specific release of drugs, a carrier‐free self‐assembled multi‐responsive nanodrug delivery system is designed, in which p‐phthalaldehyde (p‐APA) and dithiodipropionic acid are used to connect metformin (MET) and 7‐ethyl‐10‐hydroxycamptothecin (SN38) through a matrix metalloproteinase‐2 (MMP‐2) responsive peptide, and dipyridamole (DIP) is further loaded (MA‐GPLGVRGDK‐SS‐SN38@DIP, MR NPs). The MR NPs first target tumor by enhanced permeability and retention effect, then the highly expressed MMP‐2 at tumor site cleaves GPLGVRGDK, breaking the nanoparticle into three parts—DIP, MA‐GPLG, and VRGDK‐SS‐SN38. DIP automatically binds with platelets in TME, inhibiting their function and restraining tumor metastasis. MA‐GPLG releases MET in response to the acidic TME to reverse the immunosuppressive networks through PD‐L1 downregulation and M2‐like macrophages repolarization. Moreover, VRGDK‐SS‐SN38 binds to the overexpressed integrin αvβ3 receptor to achieve tumor cells specific delivery and precise killing. Overall, this study offers an intelligent spatial‐specific multi‐responsive carrier‐free drug delivery system in breast cancer, which releases drug spatial specifically, therefore reverses the tumor immunosuppressive microenvironment and inhibits metastasis.

Binder jetting 3D printing in fabricating pharmaceutical solid products for precision medicine.

Current treatment strategies are moving towards patient-centricity, which emphasizes the need for new solutions allowing for medication tailored to a patient. This can be realized by precision medicine where patient diversity is considered during treatment. However, the broader use of precision medicine is restricted by the current technological solutions and rigid manufacturing of pharmaceutical products by mass production principles. Additive manufacturing of pharmaceutical products can provide a feasible solution to this challenge. In this review, a particular subtype of additive manufacturing, that is, binder jetting 3D printing, is introduced as a solution for fabricating pharmaceutical solid products that can be considered as precision medicine. Technical aspects, practical applications, unique advantages and challenges related to this technique are discussed, indicating that binder jetting 3D printing possesses the potential for fabricating already new product prototypes, where diversity in patient treatment in terms of the needs for specific drug type, dose and drug release can be accounted. To further advance this type of mass customization of pharmaceuticals, multidisciplinary research initiatives are needed not only to cover the engineering aspects but also to bridge these innovations with patient-centric perspectives.

Development and evaluation of ciprofloxacin local controlled release materials based on molecularly imprinted polymers

The aim of this study was the molecular imprinting polymers (MIPs) assessment as a controlled release system of ciprofloxacin. The MIPs synthesis was performed by three different methods: emulsion, bulk, and co-precipitation. Lactic acid (LA) and methacrylic acid (MA) were used as functional monomers and ethylene glycol dimethacrylate as crosslinker. Also, nonimprinted polymers (NIPs) were synthesized. MIPs and NIPs were characterized by scanning electron microscopy, Fourier Transform Infrared Reflection, specific surface area, pore size, and release kinetics. Their efficiency against Staphylococcus aureus and Escherichia coli, and their cytotoxicity in dermal fibroblast cells were proven. Results show that MIPs are mesoporous materials with a pore size between 10 and 20 nm. A higher adsorption with the co-precipitation MIP with MA as a monomer was found. The release kinetics proved that a non-Fickian process occurred and that the co-precipitation MIP with LA presented the highest release rate (90.51 mg/L) in 8 h. The minimum inhibitory concentration was found between 0.031 and 0.016 mg/L for Staphylococcus aureus and between 0.004 and 0.031 mg/L for the Escherichia coli. No cytotoxicity in cellular cultures was found; also, cellular growth was favored. This study demonstrated that MIPs present promising properties for drug administration and their application in clinical practice.

Use of UMFNPs/Ce6@MBs in multimodal imaging-guided sono-photodynamic combination therapy for hepatocellular carcinoma.

Early diagnosis of liver cancer and appropriate treatment options are critical for obtaining a good prognosis. However, due to technical limitations, it is difficult to make an early and accurate diagnosis of liver cancer, and the traditional imaging model is relatively simple. Therefore, we synthesized multifunctional diagnostic/therapeutic nanoparticles, UMFNPs/Ce6@MBs, loaded with ultra-small manganese ferrite nanoparticles (UMFNPs) and chlorin e6 (Ce6). This nanoplatform can take full advantage of hypoxia, acidic pH (acidosis) and increased levels of reactive oxygen species (e.g. H2O2) in the tumor microenvironment (TME). Specific imaging and drug release can also enhance tumor therapy by modulating the hypoxic state of the TME to achieve the combined effect of sonodynamic therapy and photodynamic therapy (SPDT). In addition, the prepared UMFNPs/Ce6@MBs have H2O2 and pH-sensitive biodegradability and can release UMFNPs and photosensitizer Ce6 in the TME while producing O2 and Mn2+. The obtained Mn2+ ion nanoparticles can be used for T1 magnetic resonance imaging of tumor-bearing mice, and the released Ce6 can provide fluorescence imaging function at the same time. Because UMFNPs/Ce6@MB ultrasonic microbubbles show good ultrasonic imaging results, UMFNPs/Ce6@MBs can simultaneously provide multi-modal imaging functions for magnetic resonance imaging (MRI), ultrasound and fluorescence imaging. In conclusion, UMFNPs/Ce6@MBs realize the synergistic treatment of SDT and PDT under multi-mode near-infrared fluorescence imaging and CEUS monitoring, demonstrating its great potential in tumor precision medicine.

NANOSPONGE FOR ENHANCING SOLUBILITY AND BIOAVAILABILITY OF ORAL DRUGS: REVIEW

New developments in nanoparticle-based oral medicine have resulted in a profusion of studies to improve the solubility, permeability, and chemical stability of various medications. Nanosponges (NSs) are one type of carriers utilized in this many carrier systems. NSs are nanosized carriers with a sponge-like shape. They have hydrophilic cavities and hydrophobic branches, which aid in the loading of both hydrophilic and hydrophobic medicines. Nano-sponges have a 3-dimensional network and a nanometric cavity size. NSs are very porous, with the capacity to entrap active moieties and the advantage of controlled release. These tiny sponges circulate in the body to reach a specific place and release the medicine in a controlled and predictable manner, assisting in the resolution of numerous issues such as drug toxicity and low bioavailability. One of their significant impacts is the ability to enhance oral absorption and bioavailability. The primary goal of this review is to provide brief updates on NSs for increasing medicine oral absorption as well as their evolutions in loading drugs for enhancing their oral deliverability and treatment of a variety of diseases.

Hyaluronic Acid-Bilirubin Nanoparticles as a Tumor Microenvironment Reactive Oxygen Species-Responsive Nanomedicine for Targeted Cancer Therapy.

The tumor microenvironment (TME) has attracted considerable attention as a potential therapeutic target for cancer. High levels of reactive oxygen species (ROS) in the TME may act as a stimulus for drug release. In this study, we have developed ROS-responsive hyaluronic acid-bilirubin nanoparticles (HABN) loaded with doxorubicin (DOX@HABN) for the specific delivery and release of DOX in tumor tissue. The hyaluronic acid shell of the nanoparticles acts as an active targeting ligand that can specifically bind to CD44-overexpressing tumors. The bilirubin core has intrinsic anti-cancer activity and ROS-responsive solubility change properties. DOX@HABN showed the HA shell-mediated targeting ability, ROS-responsive disruption leading to ROS-mediated drug release, and synergistic anti-cancer activity against ROS-overproducing CD44-overexpressing HeLa cells. Additionally, intravenously administered HABN-Cy5.5 showed remarkable tumor-targeting ability in HeLa tumor-bearing mice with limited distribution in major organs. Finally, intravenous injection of DOX@HABN into HeLa tumor-bearing mice showed synergistic anti-tumor efficacy without noticeable side effects. These findings suggest that DOX@HABN has significant potential as a cancer-targeting and TME ROS-responsive nanomedicine for targeted cancer treatment.

A dual-responsive polyurethane nanocarrier for drug release triggered by intracellular GSH and NQO1 enzyme

A dual-responsive polyurethane nanocarrier was developed to achieve specific and efficient drug release triggered by elevated glutathione levels and the NQO1 enzyme unique to tumor sites.

Thermo-responsive cascade antimicrobial platform for precise biofilm removal and enhanced wound healing.

Bacterial infection, tissue hypoxia and inflammatory response can hinder infected wound repair. This study aimed to develop a multifunctional specific therapeutic photo-activated release nanosystem [HMPB@MB@AuNPs@PMB@HA (HMAPH)] by loading photosensitizer methylene blue (MB) into hollow mesoporous Prussian blue nanostructures and modifying the surface with gold particles, polymyxin B (PMB) and hydrophilic hyaluronic acid. The HMAPH was characterized using transmission electron microscopy, UV-vis, Fourier-transform infrared spectroscopy, X-ray diffraction and X-ray photon spectroscopy. The photothermal performance, iron ion release and free radical generation of the HMAPH were measured under different conditions to investigate its thermo-responsive cascade reaction. The antibacterial ability of HMAPH was investigated using live/dead fluorescence tests. The morphology and membrane integrity of Pseudomonas aeruginosa (P. aeruginosa) were investigated using transmission electron microscopy. The anti-biofilm activity of HMAPH was evaluated using crystal violet and SYBR Green I staining. Finally, we established a mouse model of a skin wound infected by P. aeruginosa to confirm the in vivo effectiveness of HMAPH. We used immunofluorescent staining, hematoxylin-eosin staining, Masson staining and enzyme-linked immunosorbent assay to examine whether HMAPH promoted wound healing and reduced inflammatory damage. In this study, hyaluronic acid was decomposed under the action of hyaluronidase. Also, the exposed nanomaterials specifically bound to the outer membrane of P. aeruginosa through PMB to increase the membrane sensitivity to photodynamic treatment. Under dual-light irradiation, a large amount of iron ions released by HMAPH underwent a Fenton reaction with H2O2 in bacteria to generate hydroxyl radicals (•OH), enabling direct killing of cells by hyperthermia. Additionally, the photodynamic activity of MB released by photo-induced activation led to the generation of reactive oxygen species, achieving synergistic and effective inhibition of P. aeruginosa. HMAPH also inhibited biofilm formation and downregulated the expression of virulence factors. In vivo experiments revealed that HMAPH accelerated the healing of P. aeruginosa-infected wounds by promoting angiogenesis and skin regeneration, inhibiting the inflammatory response and promoting M1 to M2 polarization. Our study proposed a strategy against bacteria and biofilms through a synergistic photothermal-photodynamic-Fenton reaction, opening up new prospects for combating biofilm-associated infections.

Accelerated screening of carbon dioxide capture by liquid sorbents

The sustainability potential of carbon capture, concentration, and utilization technologies motivates accelerated discovery of carbon dioxide sorbents, for which we present a high throughput screening instrument.

Brad Ligament Maneuver increases the thickness of the endometrium by more than 500%: case report

Background: Infertility affects more than one in 10 couples worldwide, but it is not well understood. Myofascial release techniques emerge as promising, but there are no studies. Aims: To describe the performance of a specific intracavitary myofascial release technique for the deep pelvis on endometrial growth. Method: The Broad Ligament Maneuver (BLM) was performed during five 10-minute sessions on consecutive days. Endometrial thickness was measured by transvaginal ultrasound and magnetic resonance imaging, before and after the intervention. Results: The thickness of the endometrium was previously 3.0 and 3.7 mm. After the intervention it increased to 18.7 mm (505.4% increase). Symptoms of endometriosis, dysmenorrhea, constipation, painful urination and sexual pain disappeared after the intervention. Conclusion: The BLM produced a 500% growth of the endometrium and eliminated the symptoms of endometriosis, dysmenorrhea, constipation, sexual and urinary pain. Most of the current idiopathic pelvic diseases must simply be of myofascial origin, a problem for which there is already effective treatment. New studies on this matter are urgently needed.

Roles of immune microenvironment in the female reproductive maintenance and regulation: novel insights into the crosstalk of immune cells.

Female fertility decline is an accumulative consequence caused by complex factors, among them, the disruption of the immune profile in female reproduction stands out as a crucial contributor. Presently, the effects of immune microenvironment (IME) on the female reproductive process have attracted increasing attentions for their dynamic but precisive roles. Immunocytes including macrophages, dendritic cells, T cells, B cells and neutrophils, with diverse subpopulations as well as high plasticity functioned dynamically in the process of female reproduction through indirect intercellular communication via specific cytokine release transduced by molecular signal networks or direct cell-cell contact to maintain the stability of the reproductive process have been unveiled. The immune profile of female reproduction in each stage has also been meticulously unveiled. Especially, the application of single-cell sequencing (scRNA-seq) technology in this process reveals the distribution map of immune cells, which gives a novel insight for the homeostasis of IME and provides a research direction for better exploring the role of immune cells in female reproduction. Here, we provide an all-encompassing overview of the latest advancements in immune modulation within the context of the female reproductive process. Our approach involves structuring our summary in accordance with the physiological sequence encompassing gonadogenesis, folliculogenesis within the ovaries, ovulation through the fallopian tubes, and the subsequent stages of embryo implantation and development within the uterus. Our overarching objective is to construct a comprehensive portrayal of the immune microenvironment (IME), thereby accentuating the pivotal role played by immune cells in governing the intricate female reproductive journey. Additionally, we emphasize the pressing need for heightened attention directed towards strategies that focus on immune interventions within the female reproductive process, with the ultimate aim of enhancing female fertility.

Assessment of calcium alginate gels as wall materials for encapsulation systems.

Calcium alginate gels are widely used to encapsulate active compounds. Some characteristic parameters of these gels are necessary to describe the release of active compounds through mechanistic mathematical models. In this work, transport and kinetics properties of calcium alginate gels were determined through simple experimental techniques. The weight-average molecular weight ( = 192 × 103 Da) and the fraction of residues of α-l-guluronic acid ( = 0.356) of sodium alginate were determined by capillary viscometry and 1 H-nuclear magnetic resonance at 25 °C, respectively. Considering the half egg-box model, both values were used to estimate the molecular weight of calcium alginate as = 2.02 × 105 Da. An effective diffusion coefficient of water ( = 2.256 × 10-9 m2 s-1 ) in calcium alginate was determined using a diffusion cell at 37 °C. Finally, a kinetics constant of depolymerization ( = 9.72 × 10-9 m3 mol-1 s-1 ) of calcium alginate was obtained considering dissolution of calcium to a medium under intestinal conditions. The experimental techniques used are simple and easily reproducible. The obtained values may be useful in the design, production, and optimization of the alginate-based delivery systems that require specific release kinetics of the encapsulated active compounds. © 2023 Society of Chemical Industry.

Smart hybrid copolymer-coated silica nanosystems with dual responsiveness as a carrier for positive charged molecules

Smart nanosystems consisting of inorganic particles and responsive polymers display significant and remarkable aspects. Such combined work exploits a facile path for multifunctional nanomaterials and facilitates various novel technological applications due to “live” polymer components. Here, we report the design and synthesis of a new platform of smart hybrid nanosystems (SHN) for positively charged probe loading and specific release under pH and temperature-controlled conditions. The SHN was prepared by a simple sequential method that produced an integrated core–shell nanomaterial with a dual stimulus response and excellent colloidal stability. Further, we demonstrate by crossing DLS and NMR results that these core–shell nanosystems present transduction from both stimuli to a mechanical shrinkage of the polymeric shell, leading to a remote-controlled dual response that can be synthetically tuned by controlling the molar ratio between monomers. Finally, we studied the potential of these SHN as molecular carriers and demonstrated that they are useful for selective ionic encapsulation of positively charged molecules, which release is controlled by the dual responsiveness. We successfully extended this concept to doxorubicin release triggered by T and pH changes, which opens possibilities of using these SHN improving results and patient compliance in chemotherapy treatments.

Effect of irradiation on thermal stability of nitric acid solutions of acetohydroxamic acid

Thermal analysis of non-irradiated and irradiated to doses of 100, 250 and 500 kGy solutions of acetohydroxamic acid in 3 or 7 mol/L HNO3 has been carried out. The temperatures of transition of oxidative processes to the autocatalytic mode ranged from 315 to 333 K. The onset temperature of the exothermic reaction, its duration and rate have been determined. The parameters characterizing the intensity of the exothermic reaction (specific heat release, self-heating value, pressure increase) decrease with increasing radiation dose, especially for solutions of acetohydroxamic acid in 7 mol/L HNO3.

FISSION PRODUCT RELEASE FROM HIGH AND LOW-ENRICHED URANIUM FUELS OF THE IVG.1M RESEARCH REACTOR

The research involved conducting resource tests on two experimental water-cooled technological channels (WCTCs) utilizing low-enriched uranium (LEU) fuel within the IVG1.M research reactor. This testing was a crucial step in the reactor's conversion from highly enriched uranium (HEU) fuel to LEU. The research focused on two key parameters, namely the specific activity and the relative release of fission products (FPs) into the coolant, to evaluate the tightnessof the fuel element cladding.A gamma-spectrometric sampling method was proposed to determine the relative releaseof FPs, which involved assessing the specific activity of the coolant, calculating the release rate (Release), the born rate (Born), and the R/B ratio of FPs. Comparative gamma-spectrometric measurements were conducted to analyze the content of FPs and activation products (AP) in the coolant of WCTCs utilizing both LEU and HEU during the tests.From the comprehensive list of detected radionuclides in the IVG.1M reactor coolant, well-identified reference radionuclides recommended for monitoringfuel element cladding tightness were carefully selected. The results of the study provided insights into the specific activity and relative release of FPs, demonstrating that quantitative values for the relative release of FPs from WCTCs using LEU and HEU fuel were comparable.

Comparison of cow's milk allergy models highlighted higher humoral and Th2 immune responses in BALB/c than C3H/HeNCrl mice

Cow's milk allergy (CMA) is common in early childhood and the incidence is increasing. However, its mechanisms of action are still not fully understood due to the range of different clinical symptoms. So far, the development of different mouse models has been the best choice to study the molecular mechanisms triggering allergy. However, the selection of suitable strains for the establishment of animal models truly representative of associated human pathologies is still a challenge. Hence, we focused on both C3H/HeNCrl and BALB/c mice to characterize their susceptibility to CMA. After intraperitoneal sensitization, BALB/c and C3H/HeNCrl strains were challenged with β-lactoglobulin (BLG), and compared in allergic symptoms and active immune response, which assessed by specific antibody production and cytokine release. At first, both groups exhibited anaphylaxis, showed specific BLG-related IgE, Th2 response and seemed both suitable for the development of CMA models. However, a detailed analysis revealed that BALB/c had both stronger humoral and Th2 immune responses, producing more antibodies (IgE and IgG/IgG1/IgG2a), and releasing higher levels of Th2-associated cytokines (IL-4, IL-5, IL-13) compared to C3H/HeNCrl mice. Therefore, BALB/c strain would represent a preferential choice in the establishment of CMA models. This study highlights the subtle differences and major outcomes in the selection of mouse strains for the development of suitable food allergy models.