Synthesis and real-time characterization of self-healing, injectable, fast-gelling hydrogels based on alginate multi-reducing end polysaccharides (MREPs).

Polysaccharide-based hydrogels are promising for many biomedical applications including drug delivery, wound healing, and tissue engineering. We illustrate herein self-healing, injectable, fast-gelling hydrogels prepared from multi-reducing end polysaccharides, recently introduced by the Edgar group. Simple condensation of reducing ends from multi-reducing end alginate (M-Alg) with amines from polyethylene imine (PEI) in water affords a dynamic, hydrophilic polysaccharide network. Trace amounts of acetic acid can accelerate the gelation time from hours to seconds. The fast-gelation behavior is driven by rapid Schiff base formation and strong ionic interactions induced by acetic acid. A cantilever rheometer enables real-time monitoring of changes in viscoelastic properties during hydrogel formation. The reversible nature of these crosslinks (imine bonds, ionic interactions) provides a hydrogel with low toxicity in cell studies as well as self-healing and injectable properties. Therefore, the self-healing, injectable, and fast-gelling M-Alg/PEI hydrogel holds substantial promise for biomedical, agricultural, controlled release, and other applications.

Injectable conductive hydrogel remodeling microenvironment and mimicking neuroelectric signal transmission after spinal cord injury.

Severe spinal cord injury (SCI) leads to dysregulated neuroinflammation and cell apoptosis, resulting in axonal die-back and the loss of neuroelectric signal transmission. While biocompatible hydrogels are commonly used in SCI repair, they lack the capacity to support neuroelectric transmission. To overcome this limitation, we developed an injectable silk fibroin/ionic liquid (SFMA@IL) conductive hydrogel to assist neuroelectric signal transmission after SCI in this study. The hydrogel can form rapidly in situ under ultraviolet (UV) light. The mechanical supporting and neuro-regenerating properties are provided by silk fibroin (SF), while the conductive capability is provided by the designed ionic liquid (IL). SFMA@IL showed attractive features for SCI repair, such as anti-swelling, conductivity, and injectability. In vivo, SFMA@IL hydrogel used in rats with complete transection injuries was found to remodel the microenvironment, reduce inflammation, and facilitate neuro-fiber outgrowth. The hydrogel also led to a notable decrease in cell apoptosis and the achievement of scar-free wound healing, which saved 45.6 ± 10.8 % of spinal cord tissue in SFMA@IL grafting. Electrophysiological studies in rats with complete transection SCI confirmed SFMA@IL's ability to support sensory neuroelectric transmission, providing strong evidence for its signal transmission function. These findings provide new insights for the development of effective SCI treatments.

Patient preferences for prophylactic regimens requiring regular injections in children and adolescents: a systematic review and thematic analysis.

BACKGROUND: At present, limited literature exists exploring patient preferences for prophylactic treatment of acute rheumatic fever (ARF) and rheumatic heart disease (RHD). Given low treatment completion rates to this treatment in Australia, where the burden of disease predominantly affects Aboriginal and Torres Strait Islander people, an improved understanding of factors driving patient preference is required to improve outcomes. Due to limited available literature, this review sought to explore treatment preferences for conditions for which the findings might be generalisable to the ARF/RHD context. OBJECTIVE: Explore treatment preferences of patients, parents/caregivers and healthcare providers towards regular injection regimens in paediatric and adolescent populations for any chronic condition. Findings will be applied to the development of benzathine penicillin G (BPG) prophylactic regimens that are informed by treatment preferences of patients and their caregivers. This in turn should contribute to optimisation of successful BPG delivery. METHODS: A systematic review of databases (Medline, Embase and Global Health) was conducted using a search strategy developed with expert librarian input. Studies were selected using a two-stage process: (1) title and abstract screen and (2) full text review. Data were extracted using a reviewer-developed template and appraised using the JBI Critical Appraisal tool. Data were synthesised according to a thematic analytical framework. RESULTS: 1725 papers were identified by the database search, conducted between 12 February 2022 and 8 April 2022, and 25 were included in the review. Line-by-line coding to search for concepts generated 20 descriptive themes. From these, five overarching analytical themes were derived inductively: (1) ease of use, (2) tolerability of injection, (3) impact on daily life, (4) patient/caregiver agency and (5) home/healthcare interface. CONCLUSIONS: The findings of this review may be used to inform the development of preference-led regular injection regimens for paediatric and adolescent patient cohorts-specifically for BPG administration in ARF/RHD secondary prophylaxis. TRIAL REGISTRATION NUMBER: Patient, parent and health personnel preferences towards regular injection regimes in paediatric and adolescent populations-a protocol for a systematic review. PROSPERO 2021 CRD42021284375. Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021284375.

Development and approval of novel injectables: enhancing therapeutic innovations.

INTRODUCTION: Novel injectables possess applications in both local and systemic therapeutics delivery. The advancement in utilized materials for the construction of complex injectables has tremendously upgraded their safety and efficacy. AREAS COVERED: This review focuses on various strategies to produce novel injectables, including oily dispersions, in situ forming implants, injectable suspensions, microspheres, liposomes, and antibody-drug conjugates. We herein present a detailed description of complex injectable technologies and their related drug formulations permitted for clinical use by the United States Food and Drug Administration (USFDA). The excipients used, their purpose and the challenges faced during manufacturing such formulations have been critically discussed. EXPERT OPINION: Novel injectables can deliver therapeutic agents in a controlled way at the desired site. However, several challenges persist with respect to their genericization. Astronomical costs incurred by innovator companies during product development, complexity of the product itself, supply limitations with respect to raw materials, intricate manufacturing processes, patent evergreening, product life-cycle extensions, relatively few and protracted generic approvals contribute to the exorbitant prices and access crunch. Moreover, regulatory guidance are grossly underdeveloped and significant efforts have to be directed toward development of effective characterization techniques.

Injection therapy for carpal tunnel syndrome: A systematic review and network meta-analysis of randomized controlled trials.

Various injectants are available for the treatment of carpal tunnel syndrome. This systematic review and network meta-analysis was conducted to investigate the effectiveness of different injection therapies in alleviating the symptoms of carpal tunnel syndrome. Various databases were searched for relevant studies from inception until May 10, 2023. Eligible studies were identified using the patient (P), intervention (I), comparison (C), and outcomes (O) model, which involved (P) participants with carpal tunnel syndrome, (I) an intervention based on injection therapy, (C) the use of placebo or another injectant as a control treatment, and (O) the measurement of clinical and electrodiagnostic outcomes of interest. A total of 18 studies were included in the analysis. The network meta-analysis revealed that platelet-rich plasma is effective in the treatment of carpal tunnel syndrome in terms of symptom and pain relief and functional improvement in both the short and long term, whereas steroids are effective only in the short term. Additionally, injections of dextrose solution may offer long-term pain relief as well as short- and long-term symptom alleviation and functional improvement. The study findings suggest that platelet-rich plasma should be used as the first-line treatment for carpal tunnel syndrome, with dextrose and steroids serving as alternative treatment options.

Beneficial Effects of Concomitant Long-Acting Injectable Antipsychotics on Time to Rehospitalization in Patients With Treatment-Resistant Schizophrenia Receiving Clozapine: A Retrospective Cohort Study.

Introduction: This study aimed to assess the association between long-acting injectable (LAI) antipsychotic prescription and the risk of psychiatric hospitalization in patients with treatment-resistant schizophrenia (TRS) receiving clozapine.Methods: In this retrospective cohort study at a single tertiary psychiatric center, we analyzed rehospitalization hazard ratios (HRs) in refractory schizophrenia patients, classified by DSM-IV-TR and DSM-5 criteria. We examined various psychotropic regimens-clozapine with or without other oral antipsychotics (OAPs) or LAI antipsychotics. Subgroups were stratified by daily clozapine dosage and previous admissions.Results: A total of 719 patients were included in the study. Analyses were conducted on all the patients over 3- month, 6-month, and 1-year periods. Patients treated with a combination of clozapine and LAI antipsychotics (CLO + LAI) had a significantly higher number of previous hospitalizations (P = .003), and a higher daily dose of clozapine (P < .001) was found in the CLO + OAP group than in the CLO (monotherapy) group and the CLO + LAI group. Patients treated with LAI antipsychotic comedication had significantly lower HRs for rehospitalization in 1 year among 3 studied groups. Moreover, the protective effects of LAI antipsychotics were observed in all the subgroups stratified by daily clozapine dosage and number of previous admissions to represent disease severity.Conclusion: The combination of clozapine and LAI antipsychotics was associated with a significantly lower risk of rehospitalization compared to both the combination of clozapine and OAPs and clozapine monotherapy. The use of LAI antipsychotics should be considered to prevent rehospitalization in patients with TRS who are already being treated with clozapine.

Comparison of growth factor levels in injectable platelet-rich fibrin obtained from healthy individuals and patients with chronic periodontitis: a pilot study.

BACKGROUND: This study aimed to assess and compare the concentrations of growth factors, white blood cells (WBCs), and platelets in injectable platelet-rich fibrin (i-PRF) derived from people with healthy periodontal conditions and those with chronic periodontitis. METHODS: Venous blood samples were obtained from 30 patients diagnosed with chronic periodontitis (test group) and 30 participants with healthy periodontal conditions (control group). The i-PRF was then acquired from centrifuged blood. The growth factors (VEGF, IGF-1, TGF-ß1, PDGF-BB and EGF) released from the i-PRF samples were compared between groups with ELISA testing. The amounts of WBCs and platelets were also compared. RESULTS: No significant differences in the concentrations of growth factors were found between the groups (the mean values for the control and test groups were, respectively: IGF: 38.82, 42.46; PDGF: 414.25, 466.28; VEGF: 375.69, 412.18; TGF-ß1: 21.50, 26.21; EGF: 138.62, 154.82). The test group exhibited a significantly higher WBC count than the control group (8.80 vs. 6.60, respectively). However, the platelet count did not show a statistically significant difference between the groups (control group 242.0 vs. test group 262.50). No significant correlation was observed between WBC count and growth factor level in either group. CONCLUSIONS: The growth factor levels in i-PRFs did not exhibit significant difference between the two groups. This suggests that the levels of these growth factors may be unaffected by the periodontal disease.

Administering injectable medications prescribed in the anticipation of the end of life in the community: A mixed-methods observational study.

BACKGROUND: The prescription of injectable anticipatory medications ahead of possible need for last-days-of-life symptom relief is established community practice internationally. Healthcare teams and policy makers view anticipatory medication as having a key role in optimising effective and timely symptom control. However, how these medications are subsequently administered (used) is unclear and warrants detailed investigation to inform interdisciplinary practice and guidance. OBJECTIVE: To identify the frequency, timing and recorded circumstances of the administration of injectable end-of-life anticipatory medications prescribed for patients living at home and in residential care. DESIGN: A retrospective mixed-methods observational study using general practitioner (family doctor) and community nursing held clinical records. SETTING(S): Community-based care in two English counties. PARTICIPANTS: 167 deceased adult patients (aged 18+) registered with eleven general practitioner practices and two associated community nursing services. These were patients prescribed anticipatory medications, identified from the 30 most recent deaths per practice. Patients died between 1 March 2017 and 25 September 2019, from any cause except trauma, sudden death or suicide. METHODS: Patient characteristics, anticipatory medication discussions, recorded administration contexts and decision-making, medication details, recorded symptom control and comfort at death were collected from clinical records. Data analysis combined quantitative and qualitative analyses in a mixed methods approach. RESULTS: Anticipatory medications were administered to 59.9 % (100/167) patients, commenced between 0 and 586 days before death (median 3 days). Their usage was similar for patients who died from cancer and non-cancer conditions. Anticipatory medications were almost universally started and titrated by visiting nurses. Eleven patients had medications started between 59 days and 586 days before death for recorded reversible non-end-of-life care conditions. Only 5 % (5/100) of patient records contained detailed accounts of patient participation in decisions to start medications: four were recorded as being reluctant to commence medications but agreed to trial injections to relieve symptoms. Crucially, there was recurrent under-recording of the effectiveness of injectable medications and patient comfort. CONCLUSIONS: Prescribed medications were commonly administered by visiting community nurses to help manage last-days-of-life symptoms. However, patient records infrequently referred to the effectiveness of administered medication and perceived patient comfort. Most recorded references to patient and family preferences for involvement in anticipatory medication decision-making and their experiences of care were brief and perfunctory. More detailed information should be routinely recorded in clinical records to enable assessment of the appropriate and effective use of anticipatory medicines and how inter-professional collaboration and services could be developed to provide adequate twenty-four-hour cover. TWEETABLE ABSTRACT: Effectiveness of injectable end-of-life symptom control medications and patient comfort often under-recorded @Ben_Bowers__ @PELi_Cam @TheQNI.

Vantris vs. deflux for treatment of paediatric vesicoureteral reflux: Efficacy and obstruction risk.

INTRODUCTION: The aim was to compare the efficacy of polyacrylate polyalcohol copolymer (PPC) injections and dextranomer/hyaluronic acid (Dx/Ha) injections for the endoscopic treatment of vesicoureteral reflux in children. MATERIAL: This retrospective cohort study included 189 young patients who had endoscopic treatment for vesicoureteral reflux from January 2012 to December 2019 in our center. Among them, 101 had PCC injections and 88 had Dx/Ha injections. Indications for treatment were vesicoureteral reflux with breakthrough urinary tract infection or vesicoureteral reflux with renal scarring on dimercaptosuccinic acid (DMSA) renal scan. Endoscopic injection was performed under the ureteral meatus. Early complications, recurrence of febrile urinary tract infection and vesicoureteral reflux after endoscopic injection, ureteral obstruction and reintervention were evaluated and compared between groups. RESULTS: Endoscopic treatment was successful in 90.1% of patients who had PPC injection and in 82% of patients who had Dx/Ha injection. Four patients presented a chronic ureteral obstruction after PPC injection, one with a complete loss of function of the dilated kidney. One patient in the Dx/Ha group presented a postoperative ureteral dilatation after 2 injections. CONCLUSION: Despite a similar success rate after PPC and Dx/Ha injections for endoscopic treatment of VUR, there may be a greater risk of postoperative ureteral obstruction after PPC injections. The benefit of using PPC to prevent febrile UTI and renal scarring in children with low-grade VUR does not seem to outweigh the risk of chronic ureteral obstruction.

Cognitive Outcomes in Nonacute Patients With Schizophrenia Treated With Long-Acting Injectable Antipsychotics Versus Oral Antipsychotics.

BACKGROUND: Patients with schizophrenia often face challenges related to cognitive function, affecting their daily functioning and overall quality of life. The choice of antipsychotic treatment may play a crucial role in determining cognitive outcomes. STUDY QUESTION: Our study aimed to investigate whether there was a difference in cognitive ability between the patients with schizophrenia receiving oral antipsychotics (OAP) versus long-acting injectable antipsychotics (LAI-APs). STUDY DESIGN: We conducted a cross-sectional study using analytical methods between January 1, 2020, and January 1, 2022. Participants were divided into 2 groups: patients undergoing treatment with OAP and patients undergoing treatment with LAI-AP. All participants underwent version A of Brief Assessment of Cognition in Schizophrenia (BACS). MEASURES AND OUTCOMES: The primary objective was to compare cognitive function in patients with schizophrenia treated with LAI antipsychotics versus OAP using BACS. Primary outcome measures include overall BACS score, with secondary measures focusing on specific cognitive domains. This study contributes to the understanding of the cognitive effects of different antipsychotic formulations in schizophrenia treatment. RESULTS: Although there was a slightly higher intelligence quotient in the LAI-AP group (102.2 vs. 101.32, P = 0.5401), it was not statistically significant. Olanzapine was the most commonly prescribed antipsychotic, with 48% of patients in the LAI-AP group and 40% in the OAP group. The LAI-AP group outperformed in all BACS evaluations. The most notable difference was in the token motor task (57.78 ± 17.03 vs. 50.04 ± 18.82, P = 0.0335), while the Tower of London test showed the smallest difference (17.26 ± 2.61 vs. 15.48 ± 3.47, P = 0.0046). Regression analysis revealed no significant variance in intelligence quotient scores; however, a significant discrepancy in BACS scores was evident, favoring the LAI treatment for better cognitive outcomes. CONCLUSIONS: The use of long-acting antipsychotic treatment in individuals with schizophrenia offers promising advantages in preserving cognitive function.

Consideration of the diameter of superficial temporal arteries related to filler injections in the temporal region.

BACKGROUND: The concavity of the temple due to adipose tissue atrophy from aging accentuates the zygomatic arch and lateral orbital rim, leading to an aged appearance. The use of hyaluronic acid filler in the temporal region has gained popularity due to its procedural simplicity and consistent outcomes. OBJECTIVE: To evaluate the safety of administering hyaluronic acid filler in the temporal region concerning the frontal branch of the superficial temporal artery, which is at risk of injury. METHODS: Empirical observations were conducted on the internal diameter of the frontal branch of the superficial temporal artery, a critical anatomical site for potential injury. RESULTS: A significant proportion of the artery segments exhibited an internal diameter below 1 mm. Given that the outer diameter of an 18-gauge cannula is 1.27 mm, this method can be considered a relatively secure approach for enhancing the temporal region. CONCLUSION: The use of an 18-gauge cannula for hyaluronic acid filler administration in the temporal region appears to be a safe and effective method, with the potential risk to the frontal branch of the superficial temporal artery being minimal.

Effectiveness and Safety of a New Hyaluronic Acid Injectable for Augmentation and Correction of Chin Retrusion.

BACKGROUND: A hyaluronic acid (HA) filler intended for non-surgical improvement of chin appearance should ideally be of high strength/firmness (high G') to allow for deep injections on the bone. HASHA (Restylane Shaype) is a new hyaluronic acid (HA) injectable with high G' and high HA concentration (25 mg/mL), engineered by the new NASHA-HD (High Definition) technology. HASHA is suitable to be placed periosteally, aiming to mimic the natural shape of the bony chin. This pivotal clinical investigation evaluated effectiveness and safety of HASHA for augmentation and correction of chin retrusion.  Methods: Subjects 18 years or older with mild or moderate chin retrusion by the Galderma Chin Retrusion Scale (GCRS), were randomized 3:1 to HASHA (n=103) or no treatment (n=37). Assessments included GCRS (blinded evaluator), aesthetic improvement (Global Aesthetic Improvement Scale [GAIS]), subject satisfaction, and safety.  Results: GCRS responder rate (1-grade or greater improvement from baseline) was significantly higher for HASHA (83.3%) versus controls (10.8%) at month 3 (P<0.001) and maintained through month 12 (P<0.001). Aesthetic improvement was high throughout the study in the HASHA group, according to investigators (97% or greater) and subjects (89% or greater). Overall, subject satisfaction was high at month 3 and maintained at month 12. Product- or injection-related adverse events were mostly mild or moderate and transient. No product- or injection-related serious adverse events were reported. CONCLUSIONS: HASHA, a new NASHA-HD injectable with extra strength/firmness, was safe and effective for chin augmentation and correction of chin retrusion, with high aesthetic improvement and subject satisfaction throughout 12 months. J Drugs Dermatol. 2024;23(4):255-261.     doi:10.36849/JDD.8145.

Intrathecal Vector Delivery in Juvenile Rats via Lumbar Cistern Injection.

Gene therapy is a powerful technology to deliver new genes to a patient for the treatment of disease, be it to introduce a functional gene, inactivate a toxic gene, or provide a gene whose product can modulate the biology of the disease. The delivery method for the therapeutic vector can take many forms, ranging from intravenous infusion for systemic delivery to direct injection into the target tissue. For neurodegenerative disorders, it is often desirable to skew transduction towards the brain and/or spinal cord. The least invasive approach to target the entire central nervous system involves injection into the cerebrospinal fluid (CSF), allowing the therapeutic to reach a large fraction of the central nervous system. The safest approach to deliver a vector into the CSF is the lumbar intrathecal injection, where a needle is introduced into the lumbar cistern of the spinal cord. This technique, also known as a lumbar puncture, has been widely used in neonatal and adult rodents and in large animal models. While the technique is similar across species and developmental stages, subtle differences in size, structure, and elasticity of tissues surrounding the intrathecal space require accommodations in the approach. This article describes a method for performing lumbar puncture in juvenile rats to deliver an adeno-associated serotype 9 vector. Here, 25-35 µL of vector were injected into the lumbar cistern, and a green fluorescent protein (GFP) reporter was used to evaluate the transduction profile resulting from each injection. The benefits and challenges of this approach are discussed.

Risk of Cardiovascular Events in Schizophrenic Patients Treated with Paliperidone Palmitate Once-Monthly Injection (PP1M): A Population-Based Retrospective Cohort Study in Taiwan.

BACKGROUND: Schizophrenia is one of the leading causes of disability. Paliperidone palmitate once-monthly injection (PP1M) was developed to provide consistent drug delivery and improve medication adherence for maintenance treatment. It is well known that patients with schizophrenia have higher cardiovascular risks, however little is known about the cardiovascular risks of patients with schizophrenia treated with PP1M in Asia. OBJECTIVE: This study aimed to estimate the incidence of cardiovascular events after initiating PP1M treatment and evaluate the cardiovascular risk associations compared with oral second-generation antipsychotics (SGAs). METHODS: Data from Taiwan's National Health Insurance Research Database were used to identify a cohort of adult patients with schizophrenia who received any SGAs from 1 March 2012 to 31 December 2018. Patients who initiated PP1M treatment were enrolled for descriptive analysis of incidence rates. PP1M patients were propensity matched 1:1 to patients initiating a new oral SGA, for comparative analysis based on demographics, clinical characteristics and treatment history at baseline, in three-step matching procedures, following the prevalent new-user design to enhance comparability. Follow-up ended at the end of the treatment episode of index drug, death, last record available, or end of the study (31 December 2019). Study endpoints included serious cardiovascular events (including severe ventricular arrhythmia and sudden death), expanded serious cardiovascular events (which further included acute myocardial infarction and ischemic stroke), and cardiovascular hospitalizations. Risks of study endpoints between matched cohorts were compared using Cox regression. RESULTS: Overall, 11,023 patients initiating PP1M treatment were identified (49.5% were females; mean age of 43.2 [12.2] years). Overall incidences for serious cardiovascular events, expanded serious cardiovascular events, and cardiovascular hospitalizations were 3.92, 7.88 and 51.96 per 1000 person-years, respectively. In matched cohort analysis (N = 10,115), the hazard ratios (HRs) between initiating PP1M and a new oral SGA for serious cardiovascular events, expanded serious cardiovascular events, and cardiovascular hospitalizations were 0.86 (95% confidence interval [CI] 0.55-1.36), 0.88 (95% CI 0.63-1.21), and 0.78 (95% CI 0.69-0.89), respectively. CONCLUSION: This study reported the population-based incidence of cardiovascular events in schizophrenic patients initiating PP1M treatment. PP1M was not associated with increased risks of serious cardiovascular events but was potentially associated with lower risks of cardiovascular hospitalizations compared with oral SGAs.

Injectable composite hydrogels embedded with gallium-based liquid metal particles for solid breast cancer treatment via chemo-photothermal combination.

Photothermal therapy (PTT) holds great promise as a cancer treatment modality by generating localized heat at the tumor site. Among various photothermal agents, gallium-based liquid metal (LM) has been widely used as a new photothermal-inducible metallic compound due to its structural transformability. To overcome limitations of random aggregation and dissipation of administrated LM particles into a human body, we developed LM-containing injectable composite hydrogel platforms capable of achieving spatiotemporal PTT and chemotherapy. Eutectic gallium-indium LM particles were first stabilized with 1,2-Distearoyl-sn­glycero-3-phosphoethanolamine (DSPE) lipids. They were then incorporated into an interpenetrating hydrogel network composed of thiolated gelatin conjugated with 6-mercaptopurine (MP) chemodrug and poly(ethylene glycol)-diacrylate. The resulted composite hydrogel exhibited sufficient capability to induce MDA-MB-231 breast cancer cell death through a multi-step mechanism: (1) hyperthermic cancer cell death due to temperature elevation by near-infrared laser irradiation via LM particles, (2) leakage of glutathione (GSH) and cleavage of disulfide bonds due to destruction of cancer cells. As a consequence, additional chemotherapy was facilitated by GSH, leading to accelerated release of MP within the tumor microenvironment. The effectiveness of our composite hydrogel system was evaluated both in vitro and in vivo, demonstrating significant tumor suppression and killing. These results demonstrate the potential of this injectable composite hydrogel for spatiotemporal cancer treatment. In conclusion, integration of PTT and chemotherapy within our hydrogel platform offers enhanced therapeutic efficacy, suggesting promising prospects for future clinical applications. STATEMENT OF SIGNIFICANCE: Our research pioneers a breakthrough in cancer treatments by developing an injectable hydrogel platform incorporating liquid metal (LM) particle-mediated photothermal therapy and 6-mercaptopurine (MP)-based chemotherapy. The combination of gallium-based LM and MP achieves synergistic anticancer effects, and our injectable composite hydrogel acts as a localized reservoir for specific delivery of both therapeutic agents. This platform induces a multi-step anticancer mechanism, combining NIR-mediated hyperthermic tumor death and drug release triggered by released glutathione from damaged cancer populations. The synergistic efficacy validated in vitro and in vivo studies highlights significant tumor suppression. This injectable composite hydrogel with synergistic therapeutic efficacy holds immense promise for biomaterial-mediated spatiotemporal treatment of solid tumors, offering a potent targeted therapy for triple negative breast cancers.

Injectable, anti-collapse, adhesive, plastic and bioactive bone graft substitute promotes bone regeneration by moderating oxidative stress in osteoporotic bone defect.

The treatment of osteoporotic bone defect remains a big clinical challenge because osteoporosis (OP) is associated with oxidative stress and high levels of reactive oxygen species (ROS), a condition detrimental for bone formation. Anti-oxidative nanomaterials such as selenium nanoparticles (SeNPs) have positive effect on osteogenesis owing to their pleiotropic pharmacological activity which can exert anti-oxidative stress functions to prevent bone loss and facilitate bone regeneration in OP. In the current study a strategy of one-pot method by introducing Poly (lactic acid-carbonate) (PDT) and ß-Tricalcium Phosphate (ß-TCP) with SeNPs, is developed to prepare an injectable, anti-collapse, shape-adaptive and adhesive bone graft substitute material (PDT-TCP-SE). The PDT-TCP-SE bone graft substitute exhibits sufficient adhesion in biological microenvironments and osteoinductive activity, angiogenic effect and anti-inflammatory as well as anti-oxidative effect in vitro and in vivo. Moreover, the PDT-TCP-SE can protect BMSCs from erastin-induced ferroptosis through the Sirt1/Nrf2/GPX4 antioxidant pathway, which, in together, demonstrated the bone graft substitute material as an emerging biomaterial with potential clinical application for the future treatment of osteoporotic bone defect. STATEMENT OF SIGNIFICANCE: Injectable, anti-collapse, adhesive, plastic and bioactive bone graft substitute was successfully synthesized. Incorporation of SeNPs with PDT into ß-TCP regenerated new bone in-situ by moderating oxidative stress in osteoporotic bone defects area. The PDT-TCP-SE bone graft substitute reduced high ROS levels in osteoporotic bone defect microenvironment. The bone graft substitute could also moderate oxidative stress and inhibit ferroptosis via Sirt1/Nrf2/GPX4 pathway in vitro. Moreover, the PDT-TCP-SE bone graft substitute could alleviate the inflammatory environment and promote bone regeneration in osteoporotic bone defect in vivo. This biomaterial has the advantages of simple synthesis, biocompatibility, anti-collapse, injectable, and regulation of oxidative stress level, which has potential application value in bone tissue engineering.

Developing an AI-based prediction model for anaphylactic shock from injection drugs using Japanese real-world data and chemical structure-based analysis.

BACKGROUND: This study aims to develop an AI-based prediction model for injection drugs that cause anaphylactic shock using Japanese Real-World Data (JADER database) and chemical structure-based analysis. METHODS: Data sourced from the JADER database included adverse drug reaction reports from April 2004 to December 2020. Only drugs with an adverse reaction named "anaphylactic shock" were selected for analysis. For model building, various models were constructed to predict anaphylactic shock-inducing drugs, such as logistic regression, LASSO, XGBoost, RF, SVM, and NNW. These models used chemical properties and structural similarities as feature variables. Dimension reduction was applied using principal component analysis. The dataset was split into training (80%) and validation (20%) sets. Six different models were trained and optimized through fivefold cross-validation. RESULTS: From April 2004 to December 2020, 947 drugs with the adverse reaction name "anaphylactic shock" were extracted from the JADER database. 320 drugs were excluded due to analytical challenges, and another 400 were removed due to their administration route. 227 drugs were finalized as target medicines. For model validation, the performance of each model was evaluated based on metrics like AUCs of ROC curve, sensitivity, and specificity. Additionally, two ensemble models, constructed from the six models were assessed using bootstrap sampling. Interestingly, it was identified that mepivacaine structural similarity had the highest importance in the final model. CONCLUSIONS: The study successfully developed an AI-based prediction model for anaphylactic shock inducing-injection drugs. The model would offer potential for drug safety evaluation and anaphylactic shock risk assessment.