Drug delivery strategies through 3D-printed calcium phosphate.

3D printing has revolutionized bone tissue engineering (BTE) by enabling the fabrication of patient- or defect-specific scaffolds to enhance bone regeneration. The superior biocompatibility, customizable bioactivity, and biodegradability have enabled calcium phosphate (CaP) to gain significance as a bone graft material. 3D-printed (3DP) CaP scaffolds allow precise drug delivery due to their porous structure, adaptable structure-property relationship, dynamic chemistry, and controlled dissolution. The effectiveness of conventional scaffold-based drug delivery is hampered by initial burst release and drug loss. This review summarizes different multifunctional drug delivery approaches explored in controlling drug release, including polymer coatings, formulation integration, microporous scaffold design, chemical crosslinking, and direct extrusion printing for BTE applications. The review also outlines perspectives and future challenges in drug delivery research, paving the way for next-generation bone repair methodologies.

Application of slow-controlled release fertilizer coordinates the carbon flow in carbon-nitrogen metabolism to effect rice quality.

Slow-controlled release fertilizers are experiencing a popularity in rice cultivation due to their effectiveness in yield and quality with low environmental costs. However, the underlying mechanism by which these fertilizers regulate grain quality remains inadequately understood. This study investigated the effects of five fertilizer management practices on rice yield and quality in a two-year field experiment: CK, conventional fertilization, and four applications of slow-controlled release fertilizer (UF, urea formaldehyde; SCU, sulfur-coated urea; PCU, polymer-coated urea; BBF, controlled-release bulk blending fertilizer). In 2020 and 2021, the yields of UF and SCU groups showed significant decreases when compared to conventional fertilization, accompanied by a decline in nutritional quality. Additionally, PCU group exhibited poorer cooking and eating qualities. However, BBF group achieved increases in both yield (10.8 t hm-2 and 11.0 t hm-2) and grain quality reaching the level of CK group. The adequate nitrogen supply in PCU group during the grain-filling stage led to a greater capacity for the accumulation of proteins and amino acids in the PCU group compared to starch accumulation. Intriguingly, BBF group showed better carbon-nitrogen metabolism than that of PCU group. The optimal nitrogen supply present in BBF group suitable boosted the synthesis of amino acids involved in the glycolysis/ tricarboxylic acid cycle, thereby effectively coordinating carbon-nitrogen metabolism. The application of the new slow-controlled release fertilizer, BBF, is advantageous in regulating the carbon flow in the carbon-nitrogen metabolism to enhance rice quality.

Controlled release of manganese and magnesium ions by microsphere-encapsulated hydrogel enhances cancer immunotherapy.

Despite the considerable potential of immune checkpoint blockade (ICB) therapy in treating various cancer types, it faces several challenges, of which the constrained objective response rate and relatively short duration of response observed in patients with cancer are the most important. This study introduces an injectable temperature-sensitive hydrogel, Pluronic F-127 (PF-127)@MnCl2/ alginate microspheres (ALG-MS)@MgCl2, that enhances the therapeutic efficacy of programmed cell death-ligand 1 (PD-L1) in cancer cells. The hydrogel material used in this study facilitated the rapid release of a significant amount of manganese ions (Mn2+) and the gradual and sustained release of magnesium ions (Mg2+) within the tumor microenvironment. This staged release profile promotes an immune microenvironment conducive to the cytotoxicity of CD8+ T cells and natural killer cells, thereby enhancing the efficacy of ICB therapy. Furthermore, the PF-127@MnCl2/ALG-MS@MgCl2 composite hydrogel exhibits the ability to convert drug-resistant tumor ("cold tumor") with a low PD-L1 response to a "hot tumor" with a high PD-L1 response. In summary, the PF-127@MnCl2/ALG-MS@MgCl2 hydrogel manipulates the immune microenvironment through the precise discharge of Mg2+ and Mn2+, thus, augmenting the efficacy of ICB therapy.

Green synthesized lignin nanoparticles for the sustainable delivery of pyraclostrobin to control strawberry diseases caused by Botrytis cinerea.

Lignin, renowned for its renewable, biocompatible, and environmentally benign characteristics, holds immense potential as a sustainable feedstock for agrochemical formulations. In this study, raw dealkaline lignin (DAL) underwent a purification process involving two sequential solvent extractions. Subsequently, an enzyme-responsive nanodelivery system (Pyr@DAL-NPs), was fabricated through the solvent self-assembly method, with pyraclostrobin (Pyr) loaded into lignin nanoparticles. The Pyr@DAL-NPs shown an average particle size of 250.4 nm, demonstrating a remarkable loading capacity of up to 54.70 % and an encapsulation efficiency of 86.15 %. Notably, in the presence of cellulase and pectinase at a concentration of 2 mg/mL, the release of Pyr from the Pyr@DAL-NPs reached 92.66 % within 120 h. Furthermore, the photostability of Pyr@DAL-NPs was significantly improved, revealing a 2.92-fold enhancement compared to the commercially available fungicide suspension (Pyr SC). Bioassay results exhibited that the Pyr@DAL-NPs revealed superior fungicidal activity against Botrytis cinerea over Pyr SC, with an EC50 value of 0.951 mg/L. Additionally, biosafety assessments indicated that the Pyr@DAL-NPs effectively declined the acute toxicity of Pyr towards zebrafish and posed no negative effects on the healthy growth of strawberry plants. In conclusion, this study presents a viable and promising strategy for developing environmentally friendly controlled-release systems for pesticides, offering the unique properties of lignin.

Triple Encapsulation and Controlled Release of Vancomycin, Rifampicin and Silver from Poly (Methyl Methacrylate) or Poly (Lactic-Co-Glycolic Acid) Nanofibers.

Although the incidence of infections in orthopedic surgeries, including periprosthetic surgeries, remains low at approximately 1-2%, the number of surgeries and the incidence of drug-resistant bacteria is increasing. The cost and morbidity associated with revision surgeries are huge. More effective drug combinations and delivery methods are urgently needed. In this paper, three anti-infective drugs (vancomycin, rifampicin, and silver sulfadiazine) have been jointly and effectively electrospun in thin (0.1 mm) flexible nanofiber mats of either poly (methyl methacrylate) (PMMA) or poly (lactic-co-glycolic acid) (PLGA). The inclusion of poly (ethylene glycol) (PEG) enabled optimal drug release with a reduced water contact angle for wetting. The controlled release of these three agents from 20% PEG (w/w to polymer)-blended PMMA or PLGA nanofiber mats may allow for the prophylactical prevention of implant-related infections or provide methods to treat orthopedic infections at the time of revision surgeries. These combinations of drugs provide excellent additive or synergistic antibiotic action against a broader spectrum of bacteria than each drug alone.

Machine learning in drug delivery.

For decades, drug delivery scientists have been performing trial-and-error experimentation to manually sample parameter spaces and optimize release profiles through rational design. To enable this approach, scientists spend much of their career learning nuanced drug-material interactions that drive system behavior. In relatively simple systems, rational design criteria allow us to fine tune release profiles and enable efficacious therapies. However, as materials and drugs become increasingly sophisticated and their interactions have non-linear and compounding effects, the field is suffering the Curse of Dimensionality which prevents us from comprehending complex structure-function relationships. In the past, we have embraced this complexity by implementing high-throughput screens to increase the probability of finding ideal compositions. However, this brute force method was inefficient and led many to abandon these fishing expeditions. Fortunately, methods in data science including artificial intelligence / machine learning (AI/ML) are providing ideal analytical tools to model this complex data and ascertain quantitative structure-function relationships. In this Oration, I speak to the potential value of data science in drug delivery with particular focus on polymeric delivery systems. Here, I do not suggest that AI/ML will simply replace mechanistic understanding of complex systems. Rather, I propose that AI/ML should be yet another useful tool in the lab to navigate complex parameter spaces. The recent hype around AI/ML is breathtaking and potentially over inflated, but the value of these methods is poised to revolutionize how we perform science. Therefore, I encourage readers to consider adopting these skills and applying data science methods to their own problems. If done successfully, I believe we will all realize a paradigm shift in our approach to drug delivery.

Impact of Fibrin Gel Architecture on Hepatocyte Growth Factor Release and Its Role in Modulating Cell Behavior for Tissue Regeneration.

A novel scaffold design has been created to enhance tissue engineering and regenerative medicine by optimizing the controlled, prolonged release of Hepatocyte Growth Factor (HGF), a powerful chemoattractant for endogenous mesenchymal stem cells. We present a new stacked scaffold that is made up of three different fibrin gel layers, each of which has HGF integrated into the matrix. The design attempts to preserve HGF's regenerative properties for long periods of time, which is necessary for complex tissue regeneration. These multi-layered fibrin gels have been mechanically evaluated using rheometry, and their degradation behavior has been studied using D-Dimer ELISA. Understanding the kinetics of HGF release from this novel scaffold configuration is essential for understanding HGF's long-term sustained bioactivity. A range of cell-based tests were carried out to verify the functionality of HGF following extended incorporation. These tests included 2-photon microscopy using phalloidin staining to examine cellular morphology, SEM analysis for scaffold-cell interactions, and scratch and scatter assays to assess migration and motility. The analyses show that the novel stacking scaffold promotes vital cellular processes for tissue regeneration in addition to supporting HGF's bioactivity. This scaffold design was developed for in situ tissue engineering. Using the body as a bioreactor, the scaffold should recruit mesenchymal stem cells from their niche, thus combining the regenerative abilities of HGF and MSCs to promote tissue remodeling and wound repair.

Release and Transport of Nanomaterials from Hydrogels Controlled by Temperature.

Understanding the transport of nanoparticles from and within hydrogels is a key issue for the design of nanocomposite hydrogels for drug delivery systems and tissue engineering. To investigate the translocation of nanocarriers from and within hydrogel networks triggered by changes of temperature, ultrasmall (8 nm) and small (80 nm) silica nanocapsules are embedded in temperature-responsive hydrogels and non-responsive hydrogels. The ultrasmall silica nanocapsules are released from temperature-responsive hydrogels to water or transported to other hydrogels upon direct activation by heating or indirect activation by Joule heating; while, they are not released from non-responsive hydrogel. Programmable transport of nanocarriers from and in hydrogels provides insights for the development of complex biomedical devices and soft robotics.

Stepwise dual-release microparticles of BMP-4 and SCF in induced pluripotent stem cell spheroids enhance differentiation into hematopoietic stem cells.

Recently, the formation of three-dimensional (3D) cell aggregates known as embryoid bodies (EBs) grown in media supplemented with HSC-specific morphogens has been utilized for the directed differentiation of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), into clinically relevant hematopoietic stem cells (HSCs). However, delivering growth factors and nutrients have become ineffective in inducing synchronous differentiation of cells due to their 3D conformation. Moreover, irregularly sized EBs often lead to the formation of necrotic cores in larger EBs, impairing differentiation. Here, we developed two gelatin microparticles (GelMPs) with different release patterns and two HSC-related growth factors conjugated to them. Slow and fast releasing GelMPs were conjugated with bone morphogenic factor-4 (BMP-4) and stem cell factor (SCF), respectively. The sequential presentation of BMP-4 and SCF in GelMPs resulted in efficient and effective hematopoietic differentiation, shown by the enhanced gene and protein expression of several mesoderm and HSC-related markers, and the increased concentration of released HSC-related cytokines. In the present study, we were able to generate CD34+, CD133+, and FLT3+ cells with similar cellular and molecular morphology as the naïve HSCs that can produce colony units of different blood cells, in vitro.

Construction of mitochondrial-targeting nano-prodrug for enhanced Rhein delivery and treatment for osteoarthritis in vitro.

Rhein, a natural anthraquinone compound derived from traditional Chinese medicine, exhibits potent anti-inflammatory properties via modulating the level of Reactive oxygen or nitrogen species (RONS). Nevertheless, its limited solubility in water, brief duration of plasma presence, as well as its significant systemic toxicity, pose obstacles to its in vivo usage, necessitating the creation of a reliable drug delivery platform to circumvent these difficulties. In this study, an esterase-responsive and mitochondria-targeted nano-prodrug was synthesized by conjugating Rhein with the polyethylene glycol (PEG)-modified triphenyl phosphonium (TPP) molecule, forming TPP-PEG-RH, which could spontaneously self-assemble into RPT NPs when dispersed in aqueous media. The TPP outer layer of these nanoparticles enhances their pharmacokinetic profile, facilitates efficient delivery to mitochondria, and promotes cellular uptake, thereby enabling enhanced accumulation in mitochondria and improved therapeutic effects in vitro. The decline in RONS was observed in IL-1ß-stimulated chondrocyte after RPT NPs treating. RPT NPs also exert excellent anti-inflammatory (IL-1ß, TNF-α, IL-6 and MMP-13) and antioxidative effects (Cat and Sod) via the Nrf2 signalling pathway, upregulation of cartilage related genes (Col2a1 and Acan). Moreover, RPT NPs shows protection of mitochondrial membrane potential and inhibition of chondrocyte apoptosis. Moreover, These findings suggest that the mitochondria-targeted polymer-Rhein conjugate may offer a therapeutic solution for patients suffering from chronic joint disorders, by attenuating the progression of osteoarthritis (OA).

Determination of antifungal efficacy and phytotoxicity of a unique silica coated porous zinc oxide nanocomposite medium for slow-release agrochemicals.

AIMS: In this study, the antifungal efficacy and phytotoxicity of silica coated porous zinc oxide nanoparticle (SZNP) were analyzed as this nanocomposite was observed to be a suitable platform for slow release fungicides and has the promise to bring down the dosage of other agrochemicals as well. METHODS AND RESULTS: Loading and release kinetics of tricyclazole, a potent fungicide, were analyzed by measuring surface area (SBET) using Brunauer-Emmett-Teller (BET) isotherm and liquid chromatography tandem mass spectrometry (LC-MS/MS), respectively. The antifungal efficacy of ZnO nanoparticle (ZNP) and SZNP was investigated on two phytopathogenic fungi (Alternaria solani and Aspergillus niger). The morphological changes to the fungal structure due to ZNP and SZNP treatment were studied by field emission-scanning electron microscopy. Nanoparticle mediated elevation of reactive oxygen species (ROS) in fungal samples was detected by analyzing the levels of superoxide dismutase, catalase, thiol content, lipid peroxidation, and by 2,7-dichlorofluorescin diacetate assay. The phytotoxicity of these two nanostructures was assessed in rice plants by measuring primary plant growth parameters. Further, the translocation of the nanocomposite in the same plant model system was examined by checking the presence of fluorescein isothiocyanate tagged SZNP within the plant tissue. CONCLUSIONS: ZNP had superior antifungal efficacy than SZNP and caused the generation of more ROS in the fungal samples. Even then, SZNP was preferred as an agrochemical delivery vehicle because, unlike ZNP alone, it was not toxic to plant system. Moreover, as silica in nanoform is entomotoxic in nature and nano ZnO has antifungal property, both the cargo (agrochemical) and the carrier system (silica coated porous nano zinc oxide) will have a synergistic effect in crop protection.

Lignin microcapsules prepared on the basis of flexible skeleton with high foliar retention and UV shielding properties.

Lignin-based microcapsules are extremely attractive for their biodegradability and photolysis resistance. However, the water-soluble all-lignin shells were unsatisfactory in terms of rainfall and foliar retention, and lacked the test of agricultural production practices. Herein, a novel microcapsule based on a flexible skeleton formed by interfacial polymerization and absorbed with lignin particles (LPMCs) was prepared in this study. Further analysis demonstrated that the shell was formed by cross-linking the two materials in layers and showed excellent flexibility and photolysis resistance. The pesticide loaded LPMCs showed about 98.68 % and 73.00 % improvement in scour resistance and photolysis resistance, respectively, as compared to the bare active ingredient. The foliar retention performance of LPMCs was tested in peanut plantations during the rainy season. LPMCs loaded with pyraclostrobin (Pyr) and tebuconazole (Teb) exhibited the best foliar disease control and optimum plant architecture, resulting in an increase in yield of about 5.36 %. LPMCs have a promising application prospect in the efficient pesticide utilization, by controlling its deformation, adhesion and release, an effective strategy for controlling diseases and managing plant growth was developed.

Highly swellable, cytocompatible and biodegradeable guar gum-based hydrogel system for controlled release of bioactive components of liquorice (Glycyrrhiza glabra L.): Synthesis and evaluation.

Glycyrrhiza glabra Linn (liquorice) has been widely used for therapeutic purposes to treat digestive disorders, immunomodulatory disorders, inflammatory disorders, diabetes, viral infections, and cancer. Liquorice contains a wide variety of bioactive compounds, including glycyrrhizin, flavonoids, and terpenoids. Several factors compromise their therapeutic efficacy, such as poor pharmacokinetic profiles and physicochemical properties. Therefore, to improve its overall effectiveness, liquorice solid dispersion (LSD) was incorporated into biopolymer-based guar gum-grafted-2-acrylamido-2-methylpropane sulfonic acid (Guar gum-g-AMPS) hydrogels designed for controlled delivery via the oral route and characterized. The qualitative analysis of LSD revealed 51 compounds. Hydrogel structural properties were assessed for their effect on swelling and release. The highest swelling ratio (6413 %) and drug release (84.12 %) occurred at pH 1.2 compared to pH 7.4 (swelling ratio of 2721 % and drug release of 79.36 %) in 48 h. The hydrogels exhibited high porosity (84.23 %) and biodegradation (9.30 % in 7 days). In vitro hemolysis tests have demonstrated the compatibility of the hydrogel with blood. CCK-8 assay confirmed the biocompatibility of the synthesized hydrogel using osteoblasts and RIN-m5f cells. LSD exhibited good anti-inflammatory activity when loaded into hydrogels after being subjected to protein denaturation experiments. Moreover, LSD-loaded hydrogels have good antioxidant and antibacterial properties.

Preparation of chitosan-hyaluronic acid microcapsules and its dynamic release behavior analysis in a 3D-printed microchannel system: Exploration and verification.

This research focuses on the challenges of efficiently constructing drug carriers and evaluating their dynamic release in vitro simulation. By using pickering emulsion and layer-by-layer self-assembly methods. The microcapsules had tea tree oil as the core material, SiO2 nanoparticles as stabilizers, and chitosan and hyaluronic acid as shell materials. The microencapsulation mechanism, as well as the effects of core-shell mass ratio and stirring, were discussed. Specifically, a dynamic circulation simulation microchannel system was designed and manufactured based on 3D printing technology. In this simulation system, the release rate of microcapsules is accelerated and the trend changes, with its behavior aligning with the Boltzmann model. The study demonstrates the advantages of self-assembled inorganic-organic drug-loaded microcapsules in terms of controllable fabrication and ease of functional modification, and shows the potential of 3D printed cyclic microchannel systems in terms of operability and simulation fidelity in drug and physiological analysis.

Remediation of petroleum-contaminated site soil by bioaugmentation with immobilized bacterial pellets stimulated by a controlled-release oxygen composite.

Bioaugmentation techniques still show drawbacks in the cleanup of total petroleum hydrocarbons (TPHs) from petroleum-contaminated site soil. Herein, this study explored high-performance immobilized bacterial pellets (IBPs) embed Microbacterium oxydans with a high degrading capacity, and developed a controlled-release oxygen composite (CROC) that allows the efficient, long-term release of oxygen. Tests with four different microcosm incubations were performed to assess the effects of IBPs and CROC on the removal of TPHs from petroleum-contaminated site soil. The results showed that the addition of IBPs and/or CROC could significantly promote the remediation of TPHs in soil. A CROC only played a significant role in the degradation of TPHs in deep soil. The combined application of IBPs and CROC had the best effect on the remediation of deep soil, and the removal rate of TPHs reached 70%, which was much higher than that of nature attenuation (13.2%) and IBPs (43.0%) or CROC (31.9%) alone. In particular, the CROC could better promote the degradation of heavy distillate hydrocarbons (HFAs) in deep soil, and the degradation rates of HFAs increased from 6.6% to 33.2%-21.0% and 67.9%, respectively. In addition, the IBPs and CROC significantly enhanced the activity of dehydrogenase, catalase, and lipase in soil. Results of the enzyme activity were the same as that of TPH degradation. The combined application of IBPs and CROC not only increased the microbial abundance and diversity of soil, but also significantly enhanced the enrichment of potential TPH-biodegrading bacteria. M. oxydans was dominant in AP (bioaugmentation with addition of IBPs) and APO (bioaugmentation with the addition of IBPs and CROC) microcosms that added IBPs. Overall, the IBPs and CROC developed in this study provide a novel option for the combination of bioaugmentation and biostimulation for remediating organic pollutants in soil.

Nanofiber-reinforced self-healing polysaccharide-based hydrogel dressings for pH discoloration monitoring and treatment of infected wounds.

The escalating global health concern arises from chronic wounds induced by bacterial infections, posing a significant threat to individuals. Consequently, an imperative exist for the development of hydrogel dressings to facilitate prompt wound monitoring and efficacious wound management. To this end, pH-sensitive bromothymol blue (BTB) and pH-responsive drug tetracycline hydrochloride (TH) were introduced into the polysaccharide-based hydrogel to realize the integration of wound monitoring and controlled treatment. Polysaccharide-based hydrogels were formed via a Schiff base reaction by cross-linking carboxymethyl chitosan (CMCS) on an oxidized sodium alginate (OSA) skeleton. BTB was used as a pH indicator to monitor wound infection through visual color changes visually. TH could be dynamically released through the pH response of the Schiff base bond to provide effective treatment and long-term antibacterial activity for chronically infected wounds. In addition, introducing polylactic acid nanofibers (PLA) enhanced the mechanical properties of hydrogels. The multifunctional hydrogel has excellent mechanical, self-healing, injectable, antibacterial properties and biocompatibility. Furthermore, the multifaceted hydrogel dressing under consideration exhibits noteworthy capabilities in fostering the healing process of chronically infected wounds. Consequently, the research contributes novel perspectives towards the advancement of intelligent and expeditious bacterial infection monitoring and dynamic treatment platforms.

Spider minor ampullate silk protein nanoparticles: an effective protein delivery system capable of enhancing systemic immune responses.

Spider silk proteins (spidroins) are particularly attractive due to their excellent biocompatibility. Spider can produce up to seven different types of spidroins, each with unique properties and functions. Spider minor ampullate silk protein (MiSp) might be particularly interesting for biomedical applications, as the constituent silk is mechanically strong and does not super-contract in water, attributed to its amino acid composition. In this study, we evaluate the potential of recombinant nanoparticles derived from Araneus ventricosus MiSp as a protein delivery carrier. The MiSp-based nanoparticles were able to serve as an effective delivery system, achieving nearly 100% efficiency in loading the model protein lysozyme, and displayed a sustained release profile at physiological pH. These nanoparticles could significantly improve the delivery efficacy of the model proteins through different administration routes. Furthermore, nanoparticles loaded with model protein antigen lysozyme after subcutaneous or intramuscular administration could enhance antigen-specific immune responses in mouse models, through a mechanism involving antigen-depot effects at the injection site, long-term antigen persistence, and efficient uptake by dendritic cells as well as internalization by lymph nodes. These findings highlight the transnational potential of MiSp-based nanoparticle system for protein drug and vaccine delivery.

Encapsulation in Alginates Hydrogels and Controlled Release: An Overview.

This review aims to gather the current state of the art on the encapsulation methods using alginate as the main polymeric material in order to produce hydrogels ranging from the microscopic to macroscopic sizes. The use of alginates as an encapsulation material is of growing interest, as it is fully bio-based, bio-compatible and bio-degradable. The field of application of alginate encapsulation is also extremely broad, and there is no doubt it will become even broader in the near future considering the societal demand for sustainable materials in technological applications. In this review, alginate's main properties and gelification mechanisms, as well as some factors influencing this mechanism, such as the nature of the reticulation cations, are first investigated. Then, the capacity of alginate gels to release matter in a controlled way, from small molecules to micrometric compounds, is reported and discussed. The existing techniques used to produce alginates beads, from the laboratory scale to the industrial one, are further described, with a consideration of the pros and cons with each techniques. Finally, two examples of applications of alginate materials are highlighted as representative case studies.

Nanomaterials in Drug Delivery: Strengths and Opportunities in Medicine.

There is a myriad of diseases that plague the world ranging from infectious, cancer and other chronic diseases with varying interventions. However, the dynamism of causative agents of infectious diseases and incessant mutations accompanying other forms of chronic diseases like cancer, have worsened the treatment outcomes. These factors often lead to treatment failure via different drug resistance mechanisms. More so, the cost of developing newer drugs is huge. This underscores the need for a paradigm shift in the drug delivery approach in order to achieve desired treatment outcomes. There is intensified research in nanomedicine, which has shown promises in improving the therapeutic outcome of drugs at preclinical stages with increased efficacy and reduced toxicity. Regardless of the huge benefits of nanotechnology in drug delivery, challenges such as regulatory approval, scalability, cost implication and potential toxicity must be addressed via streamlining of regulatory hurdles and increased research funding. In conclusion, the idea of nanotechnology in drug delivery holds immense promise for optimizing therapeutic outcomes. This work presents opportunities to revolutionize treatment strategies, providing expert opinions on translating the huge amount of research in nanomedicine into clinical benefits for patients with resistant infections and cancer.

Comparison of Sub-Ppm Instrument Response Suggests Higher Detection Limits Could Be Used to Quantify Methane Emissions from Oil and Gas Infrastructure.

Quantifying and controlling fugitive methane emissions from oil and gas facilities remains essential for addressing climate goals, but the costs associated with monitoring millions of production sites remain prohibitively expensive. Current thinking, supported by measurement and simple dispersion modelling, assumes single-digit parts-per-million instrumentation is required. To investigate instrument response, the inlets of three trace-methane (sub-ppm) analyzers were collocated on a facility designed to release gas of known composition at known flow rates between 0.4 and 5.2 kg CH4 h-1 from simulated oil and gas infrastructure. Methane mixing ratios were measured by each instrument at 1 Hertz resolution over nine hours. While mixing ratios reported by a cavity ring-down spectrometer (CRDS)-based instrument were on average 10.0 ppm (range 1.8 to 83 ppm), a mid-infrared laser absorption spectroscopy (MIRA)-based instrument reported short-lived mixing ratios far larger than expected (range 1.8 to 779 ppm) with a similar nine-hour average to the CRDS (10.1 ppm). We suggest the peaks detected by the MIRA are likely caused by a micrometeorological phenomenon, where vortex shedding has resulted in heterogeneous methane plumes which only the MIRA can observe. Further analysis suggests an instrument like the MIRA (an optical-cavity-based instrument with cavity size ≤10 cm3 measuring at ≥2 Hz with air flow rates in the order of ≤0.3 slpm at distances of ≤20 m from the source) but with a higher detection limit (25 ppm) could detect enough of the high-concentration events to generate representative 20 min-average methane mixing ratios. Even though development of a lower-cost, high-precision, high-accuracy instrument with a 25 ppm detection threshold remains a significant problem, this has implications for the use of instrumentation with higher detection thresholds, resulting in the reduction in cost to measure methane emissions and providing a mechanism for the widespread deployment of effective leak detection and repair programs for all oil and gas infrastructure.