Intra-articular injection of an extended-release flavopiridol formulation represents a potential alternative to other intra-articular medications for treating equine joint disease.

OBJECTIVE: To establish the pharmacokinetics of the cyclin-dependent kinase-9 inhibitor flavopiridol in equine middle carpal joints, using an extended-release poly lactic-co-glycolic acid (PLGA) microparticle formulation. ANIMALS: 4 healthy horses without evidence of forelimb lameness. METHODS: A 6-week longitudinal pharmacokinetic study was conducted in 2 phases (6 weeks each) in 4 healthy horses. The PLGA microparticles containing 122 µg flavopiridol in 3 mL saline were administered by intra-articular injection into 1 middle carpal joint, with empty PLGA microparticles injected into the contralateral joint as a control. Synovial fluid and plasma were collected at time points out to 6 weeks, and drug concentrations in synovial fluid and plasma were determined using validated protocols. Synovial fluid total protein and total nucleated cell count and differential, CBC, serum biochemistry, and lameness exams were performed at each of the time points. RESULTS: Synovial fluid flavopiridol averaged 19 nM at week 1, gradually reduced to 1.4 nM by 4 weeks, and was generally below the detection limit at 5 and 6 weeks. There was no detectable flavopiridol in the plasma samples, and no adverse effects were observed at any time point. CLINICAL RELEVANCE: Intra-articular injection of PLGA microparticle-encapsulated flavopiridol was well tolerated in horses, with detectable levels of flavopiridol in the synovial fluid out to 4 weeks with negligible systemic exposure. Flavopiridol is a cyclin-dependent kinase-9 inhibitor with potent anti-inflammatory and analgesic activity. The extended-release microparticle formulation promotes intra-articular retention of the drug and it may be an alternative to other intra-articular medications for treatment of equine joint disease.

Current trends in the prevention of adhesions after zone 2 flexor tendon repair.

Treating flexor tendon injuries within the digital flexor sheath (commonly referred to as palmar hand zone 2) presents both technical and logistical challenges. Success hinges on striking a delicate balance between safeguarding the surgical repair for tendon healing and initiating early rehabilitation to mitigate the formation of tendon adhesions. Adhesions between tendon slips and between tendons and the flexor sheath impede tendon movement, leading to postoperative stiffness and functional impairment. While current approaches to flexor tendon repair prioritize maximizing tendon strength for early mobilization and adhesion prevention, factors such as pain, swelling, and patient compliance may impede postoperative rehabilitation efforts. Moreover, premature mobilization could risk repair failure, necessitating additional surgical interventions. Pharmacological agents offer a potential avenue for minimizing inflammation and reducing adhesion formation while still promoting normal tendon healing. Although some systemic and local agents have shown promising results in animal studies, their clinical efficacy remains uncertain. Limitations in these studies include the relevance of chosen animal models to human populations and the adequacy of tools and measurement techniques in accurately assessing the impact of adhesions. This article provides an overview of the clinical challenges associated with flexor tendon injuries, discusses current on- and off-label agents aimed at minimizing adhesion formation, and examines investigational models designed to study adhesion reduction after intra-synovial flexor tendon repair. Understanding the clinical problem and experimental models may serve as a catalyst for future research aimed at addressing intra-synovial tendon adhesions following zone 2 flexor tendon repair.

Biomimetic Bone-Like Composite Hydrogel Scaffolds Composed of Collagen Fibrils and Natural Hydroxyapatite for Promoting Bone Repair.

Bone is a complex organic-inorganic composite tissue composed of ∼30% organics and ∼70% hydroxyapatite (HAp). Inspired by this, we used 30% collagen and 70% HAp extracted from natural bone using the calcination method to generate a biomimetic bone composite hydrogel scaffold (BBCHS). In one respect, BBCHS, with a fixed proportion of inorganic and organic components similar to natural bone, exhibits good physical properties. In another respect, the highly biologically active and biocompatible HAp from natural bone effectively promotes osteogenic differentiation, and type I collagen facilitates cell adhesion and spreading. Additionally, the well-structured porosity of the BBCHS provides sufficient growth space for bone marrow mesenchymal stem cells (BMSCs) while promoting substance exchange. Compared to the control group, the new bone surface of the defective location in the B-HA70+Col group is increased by 3.4-fold after 8 weeks of in vivo experiments. This strategy enables the BBCHS to closely imitate the chemical makeup and physical structure of natural bone. With its robust biocompatibility and osteogenic activity, the BBCHS can be easily adapted for a wide range of bone repair applications and offers promising potential for future research and development.

Allergen Immunotherapy for Asthma.

Allergen immunotherapy is a disease-modifying treatment for IgE-mediated allergies reducing disease burden and symptoms in patients with allergic rhinitis, with or without asthma. The growing evidence that allergen immunotherapy also has the potential to facilitate achieving asthma control in patients with allergic asthma resulted in its acknowledgment by international bodies (Global Initiative for Asthma and European Academy of Allergy and Clinical Immunology) as add-on treatment for mild/moderate asthma. Although there have been promising developments in biomarkers for patient selection and for allergen immunotherapy efficacy evaluation in patients with asthma, a lot more data are still required.

Solar-Driven Continuous CO2 Reduction to CO and CH4 using Heterogeneous Photothermal Catalysts: Recent Progress and Remaining Challenges.

The urgent need to reduce the carbon dioxide level in the atmosphere and keep the effects of climate change manageable has brought the concept of carbon capture and utilization to the forefront of scientific research. Amongst the promising pathways for this conversion, sunlight-powered photothermal processes, synergistically using both thermal and non-thermal effects of light, have gained significant attention. Research in this field focuses both on the development of catalysts and continuous-flow photoreactors, which offer significant advantages over batch reactors, particularly for scale-up. Here, we focus on sunlight-driven photothermal conversion of CO2 to chemical feedstock CO and CH4 as synthetic fuel. This review provides an overview of the recent progress in the development of photothermal catalysts and continuous-flow photoreactors and outlines the remaining challenges in these areas. Furthermore, it provides insight in additional components required to complete photothermal reaction systems for continuous production (e. g., solar concentrators, sensors and artificial light sources). In addition, our review emphasizes the necessity of integrated collaboration between different research areas, like chemistry, material science, chemical engineering, and optics, to establish optimized systems and reach the full potential of this technology.

Unraveling the universality of chemical fear communication: evidence from behavioral, genetic, and chemical analyses.

Abundant evidence indicates that humans can communicate threat-related information to conspecifics through their body odors. However, prior research has been primarily conducted on Western (WEIRD) samples. In this study, we aimed to investigate whether threat-related information can be transmitted by individuals of East Asian descent who carry a single-nucleotide polymorphism (SNP) 538G → A in the ABCC11 gene, which significantly reduces (noticeable) body odor. To examine this, we recruited 18 self-identified male East Asian AA-homozygotes and 18 self-identified male Western individuals who were carriers of the functional G-allele. We collected samples of their fear-related and neutral body odors. Subsequently, we conducted a double-blind behavioral experiment in which we presented these samples to 69 self-identified female participants of Western Caucasian and East Asian backgrounds. The participants were asked to rate faces that were morphed between expressions of fear and disgust. Notably, despite the "odorless" phenotypical expression of the ABCC11-mutation in East Asians, their fear odor caused a perceptual fear bias in both East Asian and Caucasian receivers. This finding leaves open the possibility of universal fear chemosignaling. Additionally, we conducted exploratory chemical analysis to gain initial insights into the chemical composition of the body odors presented. In a subsequent pre-registered behavioral study (N = 33), we found that exposure to hexadecanoic acid, an abundant compound in the fear and neutral body odor samples, was sufficient to reproduce the observed behavioral effects. While exploratory, these findings provide insight into how specific chemical components can drive chemical fear communication.

CircGNB1 drives osteoarthritis pathogenesis by inducing oxidative stress in chondrocytes.

BACKGROUND: Circular RNAs (circRNAs) have risen to prominence as important regulators of biological processes. This study investigated whether circGNB1 functions as a competitive endogenous RNA to regulate the pathological process of oxidative stress in age-related osteoarthritis (OA). METHODS: The relationship between circGNB1 expression and oxidative stress/OA severity was determined in cartilages from OA patients at different ages. The biological roles of circGNB1 in oxidative stress and OA progression, and its downstream targets were determined using gain- and loss-of-function experiments in various biochemical assays in human chondrocytes (HCs). The in vivo effects of circGNB1 overexpression and knockdown were also determined using a destabilization of the medial meniscus (DMM) mouse model. RESULTS: Increased circGNB1 expression was detected in HCs under oxidative and inflammatory stress and in the cartilage of older individuals. Mechanistically, circGNB1 sponged miR-152-3p and thus blocked its interaction with its downstream mRNA target, ring finger protein 219 (RNF219), which in turn stabilized caveolin-1 (CAV1) by preventing its ubiquitination at the K47 residue. CircGNB1 inhibited IL-10 signalling by antagonizing miR-152-3p-mediated RNF219 and CAV1 inhibition. Consequently, circGNB1 overexpression promoted OA progression by enhancing catabolic factor expression and oxidative stress and by suppressing anabolic genes in vitro and in vivo. Furthermore, circGNB1 knockdown alleviated the severity of OA, whereas circGNB1 overexpression had the opposite effect in a DMM mouse model of OA. CONCLUSION: CircGNB1 regulated oxidative stress and OA progression via the miR-152-3p/RNF219/CAV1 axis. Modulating circGNB1 could be an effective strategy for treating OA.

More (corrective) consecutive saccades after a lesion to the posterior parietal cortex.

To reach a target, primary saccades (S1s) are often followed by (corrective) consecutive saccades (S2, and potentially S3, S4, S5), which are based on retinal and extraretinal feedback. Processing these extraretinal signals was found to be significantly impaired by lesions to the posterior parietal cortex (PPC). Recent studies, however, added a more nuanced view to the role of the PPC, where patients with PPC lesions still used extraretinal signals for S2s and perceptual judgements (Fabius et al., 2020; Rath-Wilson & Guitton, 2015). Hence, it seems that a PPC lesion is not disrupting extraretinal processing per se. Yet, a lesion might still result in less reliable processing of extraretinal signals. Here, we investigated whether this lower reliability manifests as decreased or delayed S2 initiation. Patients with PPC lesions (n = 7) and controls (n = 26) performed a prosaccade task where the target either remained visible or was removed after S1 onset. When S1 is removed, accurate S2s (corrections of S1 error) rely solely on extraretinal signals. We analysed S2 quantity and timing using linear mixed-effects modelling and additive hazards analyses. Patients demonstrated slower S1 execution and lower S1 amplitudes than controls, but their S2s still compensated the S1 undershoot, also when they only relied on extraretinal information. Surprisingly, patients showed an increased amount of S2s. This deviation from control behaviour can be seen as suboptimal, but given the decreased accuracy of the primary saccade, it could be optimal for patients to employ more (corrective) consecutive saccades to overcome this inaccuracy.

Covid-19 affects taste independent of taste-smell confusions: results from a combined chemosensory home test and online survey from a large global cohort.

People often confuse smell loss with taste loss, so it is unclear how much gustatory function is reduced in patients self-reporting taste loss. Our pre-registered cross-sectional study design included an online survey in 12 languages with instructions for self-administering chemosensory tests with 10 household items. Between June 2020 and March 2021, 10,953 individuals participated. Of these, 5,225 self-reported a respiratory illness and were grouped based on their reported COVID test results: COVID-positive (COVID+, N = 3,356), COVID-negative (COVID-, N = 602), and COVID unknown for those waiting for a test result (COVID?, N = 1,267). The participants who reported no respiratory illness were grouped by symptoms: sudden smell/taste changes (STC, N = 4,445), other symptoms excluding smell or taste changes (OthS, N = 832), and no symptoms (NoS, N = 416). Taste, smell, and oral irritation intensities and self-assessed abilities were rated on visual analog scales. Compared to the NoS group, COVID+ was associated with a 21% reduction in taste (95% confidence interval (CI): 15-28%), 47% in smell (95% CI: 37-56%), and 17% in oral irritation (95% CI: 10-25%) intensity. There were medium to strong correlations between perceived intensities and self-reported abilities (r = 0.84 for smell, r = 0.68 for taste, and r = 0.37 for oral irritation). Our study demonstrates that COVID-19-positive individuals report taste dysfunction when self-tested with stimuli that have little to none olfactory components. Assessing the smell and taste intensity of household items is a promising, cost-effective screening tool that complements self-reports and may help to disentangle taste loss from smell loss. However, it does not replace standardized validated psychophysical tests.

Bilateral increase in MEG planar gradients prior to saccade onset.

Every time we move our eyes, the retinal locations of objects change. To distinguish the changes caused by eye movements from actual external motion of the objects, the visual system is thought to anticipate the consequences of eye movements (saccades). Single neuron recordings have indeed demonstrated changes in receptive fields before saccade onset. Although some EEG studies with human participants have also demonstrated a pre-saccadic increased potential over the hemisphere that will process a stimulus after a saccade, results have been mixed. Here, we used magnetoencephalography to investigate the timing and lateralization of visually evoked planar gradients before saccade onset. We modelled the gradients from trials with both a saccade and a stimulus as the linear combination of the gradients from two conditions with either only a saccade or only a stimulus. We reasoned that any residual gradients in the condition with both a saccade and a stimulus must be uniquely linked to visually-evoked neural activity before a saccade. We observed a widespread increase in residual planar gradients. Interestingly, this increase was bilateral, showing activity both contralateral and ipsilateral to the stimulus, i.e. over the hemisphere that would process the stimulus after saccade offset. This pattern of results is consistent with predictive pre-saccadic changes involving both the current and the future receptive fields involved in processing an attended object, well before the start of the eye movement. The active, sensorimotor coupling of vision and the oculomotor system may underlie the seamless subjective experience of stable and continuous perception.

Acute bone loss following SARS-CoV-2 infection in mice.

The novel coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has infected more than 650 million people worldwide. Approximately 23% of these patients developed lasting "long-haul" COVID symptoms, including fatigue, joint pain, and systemic hyperinflammation. However, the direct clinical impact of SARS-CoV-2 infection on the skeletal system including bone and joint health has not been determined. Utilizing a humanized mouse model of COVID-19, this study provides the first direct evidence that SARS-CoV-2 infection leads to acute bone loss, increased osteoclast number, and thinner growth plates. This bone loss could decrease whole-bone mechanical strength and increase the risk of fragility fractures, particularly in older patients, while thinner growth plates may create growth disturbances in younger patients. Evaluating skeletal health in patients that have recovered from COVID-19 will be crucial to identify at-risk populations and develop effective countermeasures.

Added Value of Abnormal Lymph Nodes Detected with FDG-PET/CT in Suspected Vascular Graft Infection.

Vascular graft and endograft infections (VGEI) cause a serious morbidity and mortality burden. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) imaging is frequently used in the diagnostic workup, but the additional value of abnormal (18F-FDG active and/or enlarged) locoregional lymph nodes is unknown. In this retrospective study, the additional diagnostic value of abnormal locoregional lymph nodes on 18F-FDG PET/CT imaging for VGEI was evaluated, including 54 patients with a culture-proven VGEI (defined according to the Management of Aortic Graft Infection [MAGIC] group classification) and 25 patients without VGEI. 18F-FDG PET/CT was qualitatively and quantitatively assessed for tracer uptake and pattern at the location of the vascular graft, and locoregional lymph node uptake and enlargement (>10 mm). 18F-FDG uptake intensity and pattern independently predicted the presence of VGEI by logistic regression (Χ2: 46.19, p < 0.001), with an OR of 7.38 (95% CI [1.65, 32.92], p = 0.009) and 18.32 (95% CI [3.95, 84.88], p < 0.001), respectively. Single visual assessment of abnormal locoregional lymph nodes predicted the presence of VGEI with a sensitivity of 35%, specificity of 96%, PPV of 95%, and NPV of 41%. The visual assessment of abnormal lymph nodes after qualitative assessment of 18F-FDG uptake intensity and pattern at the vascular graft location did not independently predict the presence of VGEI by logistic regression (Χ2: 3.60, p = 0.058; OR: 8.25, 95% CI [0.74, 63.37], p = 0.096). In conclusion, detection of abnormal locoregional lymph nodes on 18F-FDG PET/CT has a high specificity (96%) and PPV (95%) for VGEI. However, it did not add to currently used 18F-FDG PET/CT interpretation criteria.

Covid-19 affects taste independently of smell: results from a combined chemosensory home test and online survey from a global cohort (N=10,953).

People often confuse smell loss with taste loss, so it is unclear how much gustatory function is reduced in patients self-reporting taste loss. Our pre-registered cross-sectional study design included an online survey in 12 languages with instructions for self-administering chemosensory tests with ten household items. Between June 2020 and March 2021, 10,953 individuals participated. Of these, 3,356 self-reported a positive and 602 a negative COVID-19 diagnosis (COVID+ and COVID-, respectively); 1,267 were awaiting test results (COVID?). The rest reported no respiratory illness and were grouped by symptoms: sudden smell/taste changes (STC, N=4,445), other symptoms excluding smell or taste loss (OthS, N=832), and no symptoms (NoS, N=416). Taste, smell, and oral irritation intensities and self-assessed abilities were rated on visual analog scales. Compared to the NoS group, COVID+ was associated with a 21% reduction in taste (95% Confidence Interval (CI): 15-28%), 47% in smell (95%-CI: 37-56%), and 17% in oral irritation (95%-CI: 10-25%) intensity. In all groups, perceived intensity of smell (r=0.84), taste (r=0.68), and oral irritation (r=0.37) was correlated. Our findings suggest most reports of taste dysfunction with COVID-19 were genuine and not due to misinterpreting smell loss as taste loss (i.e., a classical taste-flavor confusion). Assessing smell and taste intensity of household items is a promising, cost-effective screening tool that complements self-reports and helps to disentangle taste loss from smell loss. However, it does not replace standardized validated psychophysical tests.

The Influence of Endplate Morphology on Cage Subsidence in Patients With Stand-Alone Oblique Lateral Lumbar Interbody Fusion (OLIF).

STUDY DESIGN: A retrospective study of prospectively collected radiographic and clinical data. OBJECTIVE: This study aims to investigate the relationship between endplate morphology parameters and the incidence of cage subsidence in patients with mini-open single-level oblique lateral lumbar interbody fusion (OLIF). METHODS: We included 119 inpatients who underwent OLIF from February 2015 to December 2017. A total of 119 patients with single treatment level of OLIF were included. Plain anteroposterior and lateral radiograph were taken preoperatively, postoperatively, and during follow-up. The correlation between disc height, endplate concave angle/depth, cage position and cage subsidence were investigated. Functional rating index (Visual Analogue Scale for pain, and Roland Morris Disability Questionnaire) were employed to assess clinical outcomes. RESULTS: Cage subsidence was more commonly seen at the superior endplates (42/119, 35.29%) than at the inferior endplates (6/119, 5.04%) (p < 0.01). More importantly, cage subsidence was significantly less in patients with superior endplates that were without concave angle (3/20, 15%) than with concave angle (37/99, 37.37%) (p < 0.05). Cage subsidence correlated negatively with preoperative anterior disc height (r = -0.21, p < 0.05), but positively with disc distraction rate (r = 0.27, p < 0.01). Lastly, the distance of cage to the anterior edges of the vertebral body showed a positive correlation (r = 0.26, p < 0.01). CONCLUSIONS: This study for the first time demonstrated that endplate morphology correlates with cage subsidence after OLIF. Since relatively flat endplates with smaller concave angle significantly diminish the incidence of subsidence, the morphology of cage surface should be taken into consideration when designing the next generation of cage. In addition, precise measurement of the disc height to avoid over-distraction, and more anteriorly placement of the cage is suggested to reduce subsidence.

Efficacy and safety of dupilumab as add-on therapy for patients with severe asthma: A real-world Dutch cohort study.

BACKGROUND: Dupilumab as add-on treatment for severe uncontrolled asthma (SA) has shown to be effective and safe by phase-III-trials. Real-world data on clinical efficacy and safety is limited. OBJECTIVE: We aim to investigate the efficacy and safety of dupilumab as add-on therapy for SA in a real-world cohort. MATERIAL AND METHODS: The primary endpoint was annually exacerbation-rate (AER). Secondary outcomes were maintenance oral corticosteroid (mOCS) dependency, asthma control (ACQ-5), pulmonary function (FEV1), quality of life (AQLQ) and frequency of reported adverse events (AEs). RESULTS: Overall, 148 patients were included. Median AER [IQR] reduced from 4.00 [2.00-5.00] at baseline to 1.00 [0.00-2.00] at 12 months (p < 0.001). mOCS-dependency reduced from 39.9% of the patients at baseline, to 20.3% at 6 months and to 14.9% at 12 months (p < 0.001). Median ACQ improved from 3.00 [2.00-3.80] at baseline to 1.80 [0.60-2.95] after 6 months and to 1.40 [0.20-2.60] after 12 months (p < 0.001). Median FEV1 (L) improved from 2.21 [1.58-2.85] to 2.50 [2.00-3.06] at 6 months and to 2.51 [1.88-3.04] after 12 months (p < 0.001). The outcomes improved most in subgroups with high eosinophils (≥300/µL) or FeNO (≥50 ppb) at baseline. AEs were reported by 45.3% (67/148), of which headache was most frequent. CONCLUSIONS: This study indicates that dupilumab as add-on therapy for SA is associated with significant improvements in exacerbation-rate, mOCS-dependency, asthma control, pulmonary function, and quality of life. These results are in line with those of previous phase-III-trials.

A two-stage digestion of whole murine knee joints for single-cell RNA sequencing.

Objective: Single-cell RNA sequencing (scRNA-seq) is a powerful technology that can be applied to the cells populating the whole knee in the study of joint pathology. The knee contains cells embedded in hard structural tissues, cells in softer tissues and membranes, and immune cells. This creates a technical challenge in preparing a viable and representative cell suspension suitable for use in scRNA-seq in minimal time, where under-digestion may exclude cells in hard tissues, over-digestion may damage soft tissue cells, and prolonged digestion may induce phenotypic drift. We developed a rapid two-stage digestion protocol to overcome these difficulties. Design: A two-stage digest consisting of first collagenase IV, an intermediate cell recovery, then collagenase II on the remaining hard tissue. Cells were sequenced on the 10x Genomics platform. Results: We observed consistent cell numbers and viable single cell suspensions suitable for scRNA-seq analysis. Comparison of contralateral knees and separate mice showed reproducible cell yields and gene expression patterns by similar cell-types. A diverse collection of structural and immune cells were captured with a majority from immune origins. Two digestions were necessary to capture all cell-types. Conclusions: The knee contains a diverse mixture of stromal and immune cells that may be crucial for the study of osteoarthritis. The two-stage digestion presented here reproducibly generated highly viable and representative single-cell suspension for sequencing from the whole knee. This protocol facilitates transcriptomic studies of the joint as a complete organ.

Topographic organization of eye-position dependent gain fields in human visual cortex.

The ability to move has introduced animals with the problem of sensory ambiguity: the position of an external stimulus could change over time because the stimulus moved, or because the animal moved its receptors. This ambiguity can be resolved with a change in neural response gain as a function of receptor orientation. Here, we developed an encoding model to capture gain modulation of visual responses in high field (7 T) fMRI data. We characterized population eye-position dependent gain fields (pEGF). The information contained in the pEGFs allowed us to reconstruct eye positions over time across the visual hierarchy. We discovered a systematic distribution of pEGF centers: pEGF centers shift from contra- to ipsilateral following pRF eccentricity. Such a topographical organization suggests that signals beyond pure retinotopy are accessible early in the visual hierarchy, providing the potential to solve sensory ambiguity and optimize sensory processing information for functionally relevant behavior.

A Fresh Look on Old Clothes: Laundry Smell Boosts Second-Hand Store Sales.

The clothing industry is one of the biggest polluters impacting the environment. Set in a sustainable environment, this study addresses whether certain ambient odors can influence the purchase of second-hand clothing. This study fulfilled three aims, increasing methodological, statistical, and theoretical rigor. First, replicating the finding that fresh laundry odor can boost purchasing behavior in a second-hand store-this time in a larger sample, using a fully counterbalanced design, in a pre-registered study. Second, assessing the effectiveness of another cleanliness priming control condition (citrus odor) unrelated to the products at hand, to test hypotheses from a hedonic vs. utilitarian model. Third, combining questionnaire data tapping into psychological processes with registered sales. The results (316 questionnaires, 6781 registered transactions) showed that fresh laundry odor significantly increased the amount of money spent by customers compared to the no smell condition, (replication) and compared to citrus odor (extension). Arguably, fresh laundry odor boosts the utilitarian value of the product at (second) hand by making it smell like non-used clothing, ultimately causing customers to purchase far greater amounts in this sustainable setting.

Production of Inhalable Ultra-Small Particles for Delivery of Anti-Inflammation Medicine via a Table-Top Microdevice.

A table-top microdevice was introduced in this work to produce ultrasmall particles for drug delivery via inhalation. The design and operation are similar to that of spray-drying equipment used in industry, but the device itself is much smaller and more portable in size, simpler to operate and more economical. More importantly, the device enables more accurate control over particle size. Using Flavopiridol, an anti-inflammation medication, formulations have been developed to produce inhalable particles for pulmonary delivery. A solution containing the desired components forms droplets by passing through an array of micro-apertures that vibrate via a piezo-electrical driver. High-purity nitrogen gas was introduced and flew through the designed path, which included the funnel collection and cyclone chamber, and finally was pumped away. The gas carried and dried the micronized liquid droplets along the pathway, leading to the precipitation of dry solid microparticles. The formation of the cyclone was essential to assure the sufficient travel path length of the liquid droplets to allow drying. Synthesis parameters were optimized to produce microparticles, whose morphology, size, physio-chemical properties, and release profiles met the criteria for inhalation. Bioactivity assays have revealed a high degree of anti-inflammation. The above-mentioned approach enabled the production of inhalable particles in research laboratories in general, using the simple table-top microdevice. The microparticles enable the inhalable delivery of anti-inflammation medicine to the lungs, thus providing treatment for diseases such as pulmonary fibrosis and COVID-19.