Background/Objectives: Connective tissue disease-associated interstitial lung disease (CTD-ILD) is linked to substantial morbidity and mortality. While nintedanib (NTB) slows lung function decline in progressive pulmonary fibrosis (PPF), real-world data—particularly regarding radiographic outcomes—remain limited. We aimed to evaluate the real-world effectiveness and tolerability of antifibrotic therapy—predominantly NTB—on radiographic and functional outcomes in a Hungarian CTD-ILD cohort. Methods: We conducted a retrospective observational cohort study including 72 patients with progressive CTD-ILD who initiated antifibrotic therapy at two Hungarian tertiary centers between January 2021 and June 2025. The primary endpoint was the proportion of patients without significant radiographic progression at 6–12 months, based on blinded assessment of paired high-resolution computed tomography (HRCT) scans by two thoracic radiologists. Secondary endpoints included changes in forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO) at 6 and 12 months, safety and tolerability, and correlations between lung function and disease-related factors. Results: The cohort comprised systemic sclerosis–ILD (n = 25), rheumatoid arthritis–ILD (n = 23), and other CTD-ILD (n = 24). Radiographic stability was observed in 65.8–78.9% of patients, with improvement most commonly seen in ground-glass opacities, while traction bronchiectasis remained largely unchanged. Radiographic disease extent showed the strongest inverse correlation with baseline FVC and DLCO (p < 0.05). Significant improvements in FVC and DLCO were observed at 6 and 12 months (p < 0.001). Antifibrotic therapy was well tolerated, including in combination with immunosuppressive treatment. Conclusions: These real-world data support the effectiveness and safety of NTB in PPF–CTD-ILD and highlight radiologic disease burden as a key determinant of functional impairment.

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease characterized by chronic pulmonary fibrosis, irreversible lung function decline, and high mortality rate. Oral nintedanib (NTB) is one of the rare anti-fibrotic drugs clinically available for managing the condition but suffers from poor bioavailability and lung delivery efficiency as well as numerous off-target adverse effects. To address these critical limitations, we developed a nanosuspension (NS) formulation of NTB (NTB-NS) for inhaled treatment of IPF. The formulation is composed entirely of FDA-approved materials, including NTB and polysorbate 80, a surfactant approved for respiratory use in a clinic, and can be freeze-dried to a powder form for long-term storage and remote shipping without perturbing the physicochemical properties and drug activity. NTB-NS locally administered via oropharyngeal administration exhibited favorable pharmacokinetics over the standard oral administration of nintedanib esylate (NTB-esy), resulting in comprehensive anti-inflammatory and anti-fibrotic effects in a mouse model of bleomycin-induced pulmonary fibrosis. Notably, locally administered NTB-NS, but not oral NTB-esy, normalized several key lung function parameters in the model despite the use of 60-fold and 3-fold lower dose and dosing frequency, respectively. The findings here may open a new avenue for the treatment of IPF and potentially other fibrotic lung diseases in the clinic.

PurposeTo investigate the effect of topical nintedanib (NTD) eye drops on alkali burn–induced corneal neovascularization (CNV) and the mechanisms involved.MethodsThe effects of NTD on the proliferation, migration, and tube-like structure formation assays were evaluated in human umbilical vein endothelial cells (HUVECs). RNA sequencing was performed to identify differentially expressed genes following NTD treatment. The expression of the RAP1A/MEK/HIF-1α axis was assessed by immunofluorescence (IF) and western blotting in HUVECs after NTD treatment. A CNV mouse model was established, and topically administered NTD eye drops three times daily for 10 consecutive days. Hematoxylin and eosin staining and IF were performed on days 3 and 7 after modeling. CNV was quantitatively analyzed after cardiac perfusion on day 10.ResultsIn vitro, NTD inhibited the proliferation, migration, and tube-like structure formation of HUVECs. RAP1 and MAPK signaling pathways were enriched by RNA sequencing analysis. NTD downregulated the expressions of RAP1A, p-MEK, p-ERK1/2, HIF-1α, VEGFA, and VEGFR2 in VEGF-stimulated HUVECs. In vivo, NTD eye drops demonstrated appropriate osmolarity and pH values. Compared to the control and vehicle groups, NTD eye drops suppressed CNV, inflammation, and the expression of LYVE1, CD31, VEGFA, and RAP1 in the cornea.ConclusionsTopical NTD administration effectively reduced alkali burn–induced CNV, which was related to the RAP1/MEK/ERK pathway. NTD could be an effective treatment strategy for CNV post-alkali injury.

Nintedanib (NTD) is an inhibitor of several tyrosine kinases whose role in the pathogenesis of idiopathic pulmonary fibrosis (IPF) is well recognized. Therefore, NTD was approved for the management of IPF about ten years ago. NTD has been demonstrated to have immunomodulatory effects in vitro. We now evaluated the effects of NTD on monocyte/macrophage phenotype isolated from IPF patients treated with NTD. Monocytes were isolated from IPF patients naïve for treatments and used as such or differentiated into M1- and M2-like macrophages. The cellular phenotype (characterized by the expression pro- and anti-fibrotic surface markers) and responsiveness (characterized by oxidative stress and cytokine expression/release) were evaluated, at T0 (before treatment starts) and after 6 months of treatment with a 150 mg capsule of NTD twice a day (T1). Following differentiation, both M1 and M2 macrophage populations, derived from monocytes isolated from patients treated with NTD, present a higher percentage of cells positive for anti-fibrotic CD80/CD86 and expressing less profibrotic CD206/CD163. Importantly, gene expression and release of the pro-fibrotic factor TGF-β were significantly decreased at T1. These results show that although it does not have a direct effect on monocyte phenotype/responsiveness, NTD in vivo appears to prime monocytes to differentiate preferentially towards an anti-fibrotic macrophage phenotype, suggesting that it has an immunomodulatory effect on macrophage polarization. This data leads us to hypothesize that NTD could also induce this change in vivo, thus contributing to the improvement of the patient's fibrotic state.

Pulmonary fibrosis (PF) is a progressive interstitial lung disease characterized by high morbidity and limited treatment options. Current antifibrotic agents, such as pirfenidone and nintedanib (NIN), are restricted by systemic toxicity and insufficient pulmonary targeting. This study aimed to develop an inhalable human serum albumin (HSA)-based nanoparticle system co-delivering NIN and dihydroartemisinin (DHA), termed DHA/NIN@HSA, to achieve efficient lung-targeted combinational therapy against PF. DHA/NIN@HSA nanoparticles were prepared via a self-assembly strategy and characterized for morphology, particle size, and drug-loading efficiency. Pulmonary deposition and retention profiles after airway inhalation were evaluated using in vivo fluorescence imaging. The antifibrotic efficacy and safety of DHA/NIN@HSA were further assessed in a bleomycin-induced PF mouse model. DHA/NIN@HSA nanoparticles exhibited uniform particle size (125 ± 5 nm) and excellent pulmonary deposition, ensuring prolonged lung retention and reduced systemic exposure. Airway administration of DHA/NIN@HSA every 48h significantly mitigated fibrosis progression, improved survival, and restored alveolar architecture. Mechanistically, NIN inhibited fibroblast proliferation and myofibroblast differentiation, while DHA suppressed transforming growth factor-β1 (TGF-β1)/Smad2/3 signaling and inflammatory cytokines expression. Notably, DHA showed antifibrotic efficacy comparable to NIN with superior anti-inflammatory activity, highlighting its therapeutic potential in PF. Airway co-delivery of DHA/NIN@HSA achieved maximal antifibrotic efficacy, precise lung targeting, and favorable safety, providing a translatable nanotherapeutic platform for combinational therapy of PF.

Epidural fibrosis (EF) is a major contributor to postoperative morbidity following laminectomy. This study investigated the antifibrotic, anti-inflammatory, and anti-angiogenic effects of nintedanib (NIN), a multi-tyrosine kinase inhibitor, in a rat model of post-laminectomy EF. Twenty-one male Wistar albino rats were assigned to three groups: Control, Laminectomy (LAM), and Laminectomy + Nintedanib (NIN). The laminectomy procedure was performed at the L3 level. NIN administration, following laminectomy, was administered orally at a dose of 50 mg/kg/day for 28 days. Histopathological evaluations included hematoxylin-eosin staining for dura mater thickness and fibroblast density, and Masson's trichrome staining for collagen deposition and adhesion grading. α-smooth muscle actin (α-SMA) expression was evaluated using immunohistochemistry and RT-qPCR. Gene expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), vascular endothelial growth factor (VEGF), platelet-derived growth factor receptor (PDGFR), and transforming growth factor-β1 (TGF-β1) was quantified to characterize inflammatory, angiogenic, and fibrogenic responses. Statistical comparisons were conducted using one-way ANOVA or Kruskal-Wallis tests with appropriate post hoc analyses. The LAM group exhibited marked post-laminectomy changes, including increased dura mater thickness (8.20 ± 0.23 µm vs. 3.93 ± 0.08 µm in controls, p < 0.0001), elevated fibroblast density (p = 0.0006), severe collagen deposition, and high-grade epidural adhesions (Grade 3, p = 0.0006). NIN treatment attenuated these alterations, reducing dura mater thickness (4.80 ± 0.20 µm, p < 0.0001 vs. LAM), fibroblast density (p < 0.01), and adhesion grade (Grade 1, p = 0.0012). α-SMA immunoreactivity was high in LAM (Grade 3, p < 0.0001), whereas NIN significantly suppressed myofibroblast activation (Grade 1, p = 0.0012). NIN also significantly downregulated inflammatory mediators TNF-α (p < 0.001) and IL-1β (p < 0.001), as well as angiogenic markers VEGF (p < 0.001) and PDGF (p < 0.001), and fibrogenic mediators TGF-β1 (p < 0.001) and α-SMA (p < 0.01). These findings indicate that NIN suppresses fibroblast activation, extracellular matrix accumulation, and myofibroblast differentiation, thereby limiting epidural adhesion and scar maturation. Nintedanib effectively mitigated epidural fibrosis after laminectomy through combined antifibrotic, anti-inflammatory, and anti-angiogenic actions. By improving the dural structure and reducing key molecules that contribute to scar formation, NIN shows significant promise as a treatment to prevent postoperative epidural adhesions. Future studies with extended follow-up may help clarify its clinical relevance.

Background: Nintedanib (NIN), an intracellular inhibitor of tyrosine kinases that inhibits processes fundamental to the progression of pulmonary fibrosis (PPF), is used in the treatment of patients with PPF associated with systemic sclerosis. During NIN therapy, adverse events lead to a permanent dose reduction and treatment discontinuation. Therapeutic drug monitoring (TDM) can be used to manage and optimize drug administration based on the measurement of drug concentrations. Therefore, TDM can be helpful in minimizing the impact of adverse events and help patients remain in therapy. The aim of this study was to develop and validate a new bioanalytical UPLC-MS/MS method enabling the determination of NIN and its active metabolite in the plasma of patients with PPF associated with systemic sclerosis. Methods: Sample preparation was carried out using protein precipitation with an extraction mixture: acetonitrile neutralized with 2 M sodium carbonate. Analytes and the internal standard (intedanib-d3) were monitored using mass spectrometry (MS) and positive-ion-mode electrospray ionization by MRM. Chromatographic analysis was performed on a Zorbax SB-C18 column kept at 40 °C using isocratic elution. The mobile phase contained 0.1% formic acid in water; acetonitrile (35:65 v/v) was pumped at a flow rate of 0.3 mL/min. The analysis time was 5 min. Results: The method was verified according to the EMA guidelines over a concentration range of 2.00–200.00 ng/mL. The correlation coefficients for the calibration curves were found to be 0.9991 and 0.9957 for NIN and its metabolite BIBF 1202, respectively. The within- and between-run precision and accuracy of LLOQ were evaluated for NIN and BIBF 1202 to be within RSD 2.96%, 4.53%, 5.51%, and 6.72% and in the ranges of 102.2–107.3%, 98.0–101.8%, 104.3–114.2%, and 99.1–104.9, respectively. The stability of the analytes in plasma after 4 h at 30 °C was found to be satisfactory, meeting the assumed bias criteria below 15%. Conclusions: The proposed method was successfully applied to analyze two active compounds—NIN and BIBF 1202—in plasma samples at two time points: trough (pre-dose concentration) and 2–3 h (maximum concentration) after the administration of NIN.

Quantitative HRCT as a surrogate outcome measure for nintedanib treatment in systemic sclerosis-interstitial lung disease and idiopathic pulmonary fibrosis.

Background. Nintedanib (NTD) has been shown to be useful to slow functional decline of progressive fibrosing interstitial lung disease also in Autoimmune Systemic Diseases (ASDs) beside systemic sclerosis (SSc) and rheumatoid arthritis (RA) after the positive results of the INBUILD trial. Here we describe the effectiveness and safety of NTD in ASDs in a real-life setting. Materials and Methods. The clinical data of ASDs patients with ILD (excluded SSc and RA) treated with NTD from 17 Italian centres were retrospectively evaluated at 12 months prior to NTD introduction; at baseline, and at 12 months after NTD introduction. The following parameters were recorded: ASD clinical features, NTD tolerability, pulmonary function tests (PFTs). Progressors were defined as a drop in %pFVC &gt;= 5 and/or %pDLCO &gt;= 10 within 12 months. Results. 114 ASD-ILD patients (46.5% male, mean age 69 ± 10 years, median disease duration 5.5 (2-12) years) treated with NTD were identified. Disease features are summarized in Table 1. The most common ASD was anti-synthetase syndrome (31, 27.2%) and the most common antibody was anti-Ro52 (44, 38.6%), most (57.9%) had been previously treated with immunosuppressants. At baseline, 107 (93.9%) patients were on immunosuppressants (see Table 1), with 74 (64.9%) patients on steroid with a median dose of 5 (1.25 – 7.5). Baseline HRCT was available in 109 patients and it showed an UIP pattern in 43 (39.4%) and a NSIP pattern in 66 (60.6%) patients. A significant decline in %pFVC and in %pDLCO was observed in the 12 months prior to NTD introduction (82.4 ± 21 versus 71 ± 16, p &lt;0.001 and 51 ± 17 versus 44 ± 13, p &lt;0.001, respectively) with 54 (69%) being classified as progressors. At 12 months after NTD introduction, follow-up data were available for 54 patients and they showed an improvement in both %pFVC (72 ± 15 to 75 ± 17, p &lt; 0.001) and %pDLCO (43 ± 15 to 45 ± 17; p &lt; 0.001); moreover, the percentage of progressors was significantly lower (69% versus 26%, p &lt; 0.001). The dosage of NTD was reduced to 100 mg BID in 44 (38.6%) patients after a median time of 5 (3 – 9) months, and suspended in 19 (16.7%) patients after a median time of 3 (1-8) months, see Figure 1. During the follow-up, 10 (8.8%) patients died. Conclusions. In a real-life clinical scenario, NTD, in combination with immunosuppressants, may improve lung function in patients with ASDs. NTD seems to be well-tolerated and the rate of drug suspension is low. Our data support early evaluation of ILD in wide range of ASDs in order to identify patients eligible for antifibrotic drug in association to immunosuppressants.

Evaluating the bioavailability and therapeutic efficacy of nintedanib-loaded novasomes as a therapy for non-small cell lung cancer.

Evaluating the efficacy of nintedanib-invasomes as a therapy for non-small cell lung cancer.

Synergistic effects of heterophyllin B with nintedanib against experimental pulmonary fibrosis in mice.

Abstract Rationale: Nintedanib (NIN) is to date used for treatment of idiopathic pulmonary fibrosis ( IPF) for more than 10 years. This tyrosine-kinase inhibitor showed effect on both, lung function decline, in clinical trials, and on overall survival, in real world. However there is a lack of data on the long-term effect of NIN on survival in patients with IPF with different phenotypes. We investigated the outcome associated with NIN in a large multicentre real-world observational cohort of IPF patients. The different phenotypes were defined by the following patient characteristics at the start of follow-up: age, sex, FVC and dyspnoea by NYHA functional class. Methods: The analysis included IPF patients treated with nintedanib (NIN) and those not receiving antifibrotic treatment (NAF); both groups were enrolled into the EMPIRE registry in 2015-2020. The patients were stratified according to sex, age (&amp;lt;60, 60-70 and &amp;gt;70 years), FVC predicted (&amp;gt;80%; 50-80% and &amp;lt;50%) and dyspnoea (NYHA FC). All-cause mortality was the main endpoint. Cox proportional hazard models were built for overall survival (OS) with treatment (NIN vs NAF) as the dependent variable. Sex, age, FVC predicted, and dyspnoea were analysed as effect-modifying variables. Using this model, survival for different subgroups was estimated.Results: A total of 869 NIN and 691 NAF patients were eligible for the analysis. NIN therapy reduced the overall risk of mortality in the total cohort by 60 % (adjusted hazard ratio [HR] 0.40; 95% CI 0.30 to 0.53, p &amp;lt; 0.001). The most significant difference between NIN and NAF in OS rates was seen in patients with higher age (&amp;gt;70 years) and functionally advanced disease (FVC&amp;lt;50%) and NYHA FC of III or IV (HRs for mortality in subgroups ranging between 0.20 to 0.37 for men and 0.33 to 0.61 in women).Conclusions: We observed that NIN therapy significantly reduced differences in OS between the subgroups of IPF patients. This survival difference was most marked in men, elderly patients presenting with low FVC and worse dyspnoea at the time of diagnosis. These observational data indicate that NIN might be particularly beneficial for the patients with severely impaired functional status (lung function, NYHA); however, interpretation must be cautious due to the possibility of diagnostic bias or selection bias.Trial registration: EMPIRE was registered as a non-interventional post-registration study at the State Institute for Drug Control of the Czech Republic under ID 1412080000 on 8 December 2014.

Abstract Rationale: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease characterized by progressive scarring of the lung and associated with a high burden of disease and early death. Under pathologic conditions and in the presence of transforming growth factor beta 1 (TGF-β1), fibroblasts accumulate in areas of damage and differentiate into myofibroblasts that secrete collagen, markers of myofibroblast differentiation and fibrogenesis, and ECM markers for pulmonary fibrosis development. Previous in vitro data showed that Lactobacilli treatment attenuated key biomarkers TGFβ1, COL1A1, COL1A2, ɑ-SMA, and fibronectin in LL29 lung fibroblasts, human bronchial epithelial cells, and PMA-differentiated THP1 monocytes, suggesting potential beneficial effect in slowing IPF development. As Lactobacilli are lactic acid producers, we hypothesized that lactic acid would alter signatures of lung fibrosis in an IPF mouse model. Methods: Bleomycin mouse model: 10–12-week-old wild-type C57BL/6 mice were exposed to a PBS control or bleomycin (0.02 IU/mouse) intratracheally on Day 1 and Day 4. Each group n=6. Starting on Day 11, the mice were treated with PBS or lactide (LA) intratracheally every other day for 2 weeks along the IPF anti-fibrotic nintedanib (NIB) individually or in combination. On Day 21, the mice were euthanized for tissue harvest. Bronchopulmonary lavage (BAL) fluid and serum were collected for TGFβ1 ELISA. Histology was performed on half lung (H&amp;E staining) and RNA and protein extracted from the other half lung for downstream analysis (qPCR, Western blots). Standardized quantification of pulmonary fibrosis was done in histological samples by Ashcroft score (grade of fibrosis scale 0-8). Results: Lactic acid treatment was more effective ([asterisk][asterisk][asterisk]p&amp;lt;0.001) in reducing fibrosis markers (TGFβ1, COL1A1, COL1A2 mRNA) compared to NIB ([asterisk]p&amp;lt;0.05) or NIB+LA ([asterisk][asterisk]p&amp;lt;0.01) combination, respectively. Reduced fibrosis (mild, grade 3) was observed in LA-treated mice as compared to total fibrosis (grade 8) and healthy lungs (grade 0). Statistical analysis was performed using one-way ANOVA with Tukey's multiple comparison test (GraphPad Prism version 9.2). Data was reported as mean ± standard deviation, and representative of at least two independent experiments. Conclusion: Lung fibrosis severity and key biomarkers like TGFβ1, COL1A1 and COL1A2 were attenuated by LA treatment, suggesting potential beneficial effect in IPF development.

PurposeIdiopathic pulmonary fibrosis (IPF) is a life-threatening, progressive lung disease with limited therapeutic options, often resulting in poor patient outcomes. Current treatments, such as Nintedanib (NTB) and Pirfenidone (PFD), require frequent administration, leading to adverse effects and low patient adherence. The purpose of this study was to investigate a sustained-release drug delivery system utilizing microparticles (MPs) composed of insoluble beta-cyclodextrin (β-CD) polymers to enhance the bioavailability and extend the release of NTB and PFD.MethodsA multidisciplinary approach, including in silico modeling, in vitro assays, and in vivo studies, was employed to assess the efficacy of β-CD-polymer MPs as drug carriers.ResultsMolecular docking simulations and surface plasmon resonance studies demonstrated a stronger binding affinity of NTB to β-CD-polymer MPs compared to PFD, suggesting an extended delivery profile for NTB over PFD. Pharmacokinetic analysis in healthy mice confirmed sustained-release profiles for both drugs, with NTB maintaining therapeutic plasma concentrations for over 70 h. In a bleomycin-induced IPF mouse model, NTB-loaded β-CD-polymer MPs significantly reduced pro-inflammatory markers and required fewer injections than the standard daily NTB regimen.ConclusionThese findings indicate that β-CD-polymer MPs may serve as a promising platform for reducing dosing frequency of NTB and enhancing therapeutic outcomes in the treatment of IPF.

Purpose To investigate the efficacy of nanoparticles in treating proliferative vitreoretinopathy (PVR) through clinical observation, histology, and immunohistochemistry, despite unsatisfactory surgical outcomes and failed therapies for the current PVR treatment Design Twelve rabbits were divided into control and nintedanib (NTB) groups. The rabbits underwent weekly ophthalmologic examinations over a period of four weeks. Methods At the end of the fourth week, the rabbits’ eyes were removed for histological and immunohistochemical evaluation. Three additional rabbits outside the PVR model were administered a 0.5% NTB-loaded liposomal formulation in one eye. The drug concentrations in the vitreous samples were determined using high-pressure liquid chromatography on days 1, 7, 14, and 35. Results The PVR stages were low in the NTB group, and there was no significant difference between the NTB and control groups (p = 0.108). However, it is worth noting that the group treated with NTB had significantly fewer epiretinal membrane formations during the histological evaluation. In addition, the corrected fluorescence intensity measurement of the subjects for collagen-1 in the NTB group was significantly lower than that in the control group (p = 0.004). Most importantly, no significant adverse effects were observed. Conclusions Our study has provided preclinical support for a liposomal formulation containing NTB that, with single-dose administration, has the potential to be effective in vivo in preventing the development of PVR and its correlated pathologies without causing any significant side effects.

ObjectiveThe aim of this study is to assess the efficacy and safety of nintedanib (NTD) therapy in a real world population of patients with connective tissue diseases related interstitial lung disease (CTDs-ILD).MethodsOur multicenter retrospective study included patients with a CTD-ILD diagnosis who started NTD treatment due to the development of PPF during follow-up. The results of the percentage predicted forced vital capacity (%pFVC) and percentage predicted diffusion capacity (%pDLCO) of patients before NTD treatment and 6, 12 and 18 months after the start of NTD treatment were evaluated. In addition, the patients were divided into two groups, SSc-ILD and other CTDs-ILD, and compared in terms of the efficacy and safety of the NTD.ResultsIn all patients (n = 66), %pFVC and %pDLCO values stabilised after 6, 12 and 18 months compared to baseline values. All patients received at least one immunosuppressive therapy in combination with NTD treatment. The most common side effect after NTD treatment was diarrhoea (n = 20, 30.3%). When we divided the patients into two groups, SSc-ILD (n = 35) and other CTDs-ILDs (n = 31), no significant difference was found between the groups in the change in %pFVC (p values = 0.498, 0.595 and 0.376, respectively) and in the change in %pDLCO (p values = 0.817, 0.185 and 0.399, respectively) at 6, 12 and 18 months follow-up. Again, there was no statistically significant difference between the two groups in terms of adverse events and safety data after NTD treatment (p > 0.05).ConclusionIn summary, the use of NTD in combination with immunosuppressive therapies was effective and safe in SSc-ILD patients as well as in other CTDs-ILD patients.Key Points• This multicenter study provides real-world data on the use of nintedanib in patients with connective tissue disease-interstitial lung disease.• Nintedanib treatment is as effective and safe in patients with other connective tissue disease as in patients with systemic sclerosis.

To investigate the efficacy of nanoparticles in treating proliferative vitreoretinopathy (PVR) through clinical observation, histology, and immunohistochemistry, despite unsatisfactory surgical outcomes and failed therapies for the current PVR treatment. Twelve rabbits were divided into control and nintedanib (NTB) groups. The rabbits underwent weekly ophthalmologic examinations over a period of four weeks. At the end of the fourth week, the rabbits' eyes were removed for histological and immunohistochemical evaluation. Three additional rabbits outside the PVR model were administered a 0.5% NTB-loaded liposomal formulation in one eye. The drug concentrations in the vitreous samples were determined using high-pressure liquid chromatography on days 1, 7, 14, and 35. The PVR stages were low in the NTB group, and there was no significant difference between the NTB and control groups (p = 0.108). However, it is worth noting that the group treated with NTB had significantly fewer epiretinal membrane formations during the histological evaluation. In addition, the corrected fluorescence intensity measurement of the subjects for collagen-1 in the NTB group was significantly lower than that in the control group (p = 0.004). Most importantly, no significant adverse effects were observed. Our study has provided preclinical support for a liposomal formulation containing NTB that, with single-dose administration, has the potential to be effective in vivo in preventing the development of PVR and its correlated pathologies without causing any significant side effects.

Monitoring nintedanib (NTB) using reliable analytical methods is essential for ensuring safe dosing, minimizing toxicity, assessing drug–drug interactions, and supporting quality control in personalized cancer therapy. In this work, we present a cost-effective and energy-efficient hydrothermal strategy for synthesizing nitrogen-doped carbon dots (CDs) from disposable plastic syringes. The process, carried out at 200 °C following a calcination pretreatment, not only provides a sustainable route for valorizing biomedical waste but also addresses pressing environmental challenges. The as-prepared CDs exhibited intense green fluorescence, outstanding photostability, and a high quantum yield of 46.42%, reflecting their superior optical performance. Upon exposure to NTB, a concentration-dependent quenching response at 470 nm was observed, primarily mediated by the inner filter effect (IFE). This mechanism enabled highly sensitive NTB detection, with an ultralow detection limit of 2.5 nM (S/N = 3). The probe demonstrated remarkable selectivity, showing negligible interference from common coexisting ions, biomolecules, and anticancer drugs. Analytical accuracy was validated by recovery studies in spiked serum and urine samples, which ranged from 97.6% to 103.2%, while RSD values below 3.48% confirmed excellent precision and reproducibility. These findings establish the proposed CD-based probe as a robust, reproducible, and clinically relevant tool for NTB quantification. By demonstrating the conversion of discarded medical plastics into high-value nanomaterials, this work presents a strategy that aligns with the goals of green nanotechnology and delivers a practical platform for bioanalytical sensing, therapeutic drug monitoring, and pharmacokinetic studies. The dual focus on waste repurposing and clinical utility underscores the potential the potential of syringe plastic-derived CDs for translation into next-generation biomedical diagnostics.

Background/objectives: Idiopathic pulmonary fibrosis (IPF) is a prevalent interstitial lung disease that typically progresses gradually, leading to respiratory failure and ultimately death. IPF can be treated with the tyrosine kinase inhibitor, nintedanib (NTD), owing to its anti-fibrotic properties, which ameliorate the impairment of lung function. This study aimed to formulate, optimize, and assess NTD-loaded ufasomes (NTD-UFSs) as a nanosystem for its pulmonary targeting to snowball the bioavailability and therapeutic efficacy of the drug. Methods: To investigate the influence of numerous factors on NTD-UFSs assembly and to determine the optimal formulation, Box-Behnken statistical design was implemented with the assistance of Design-Expert® software. The thin-film hydration strategy was employed to fabricate NTD-UFSs. The optimum NTD-UFSs formulation was subsequently selected and subjected to additional evaluations. Also, using a rat model, a comparative pharmacokinetic analysis was scrutinized. Results: The optimal NTD-UFSs elicited an accumulative release of 65.57% after 24 h, an encapsulation efficiency of 62.51%, a zeta potential of -36.07 mV, and a vesicular size of 364.62 nm. In addition, it disclosed remarkable stability and a continuous cumulative release pattern. In vivo histopathological studies ascertained the tolerability of NTD-UFSs administered intratracheally. According to the pharmacokinetic studies, intratracheal NTD-UFSs administration manifested a significantly higher AUC0-∞ value than oral and intratracheal NTD suspensions, by approximately 5.66- and 3.53-fold, respectively. Conclusions: The findings of this study proposed that UFSs might be a promising nanoparadigm for the non-invasive pulmonary delivery of NTD.