Abiraterone acetate is a prodrug of abiraterone used in combination with prednisone as a standard therapeutic strategy for hormone-resistant prostate cancer (mCRPC). Due to the poor solubility and permeability, the release and absorption of abiraterone acetate are low and reduce its bioavailability. In this project, abiraterone acetate tablets prepared using nanocrystal technology were developed to overcome the drawbacks of normal tablets by enhancing in vitro dissolution rate and oral bioavailability. The abiraterone acetate nanocrystal suspensions were prepared by top-down wet milling method using a planetary ball mill with the mixture of Poloxamer 407 and Poloxamer 188 as the optimized stabilizer at a ratio of 7:1. The optimized nanocrystals were freeze-dried and characterized using DLS, TEM, DSC, and XRD. The abiraterone acetate nanocrystal tablets significantly improve the in vitro dissolution rate of abiraterone acetate compared to raw materials. Although exhibiting a similar dissolution rate compared to the Zytiga^® tablets, the nanocrystal tablets significantly improve the oral bioavailability with C_max and AUC_0–t being 3.51-fold and 2.80-fold higher, respectively, in the pharmacokinetic study. The present data indicate that nanocrystal is a promising strategy for improving the dissolution and bioavailability of abiraterone acetate.

Ferroptosis, a regulated form of cell death driven by iron-dependent lipid peroxidation, has emerged as a promising strategy for cancer therapy.

Chronic obstructive pulmonary disease (COPD), a respiratory disorder characterized by airway remodeling within a chronic inflammatory microenvironment, affects millions worldwide. Cigarette smoke, the primary etiological factor, triggers chronic pulmonary inflammation and respiratory epithelial cell senescence, rendering anti-inflammatory strategies pivotal for alleviating COPD progression and pulmonary aging. This study demonstrates that A33, a highly selective phosphodiesterase 4B inhibitor, potently attenuates chronic inflammation by suppressing nuclear factor kappa-B (NF-κB) activation in damaged epithelial cells and reducing the secretion of pro-inflammatory cytokines. Additionally, A33 exhibits senolytic potential by regulating the senescence-associated secretory phenotype (SASP) in senescent cells. A33 encapsulated liposomes decorated with mPEG (incorporating 5% DSPE-mPEG in the formulations) exhibited satisfactory stability and enhanced respiratory mucus penetration ability, successfully improving the effective pulmonary epithelial delivery of A33. Both in vitro and in vivo experiments show that mPEG-decorated A33-encapsulated liposomes enhance pulmonary mucus penetration and enable efficient intracellular delivery. In a cigarette smoke extract-induced mouse model, A33 treatment significantly inhibited COPD progression and improved pulmonary senescence, validating its therapeutic efficacy. Collectively, these findings introduce a promising local treatment strategy for COPD.

Cardiovascular diseases induced by arterial thrombosis, such as myocardial infarction and ischemic stroke, have gradually emerged as critical threats to human life and health. Sequentially targeted delivery systems are highly desired to be developed to improve the delivery of thrombolytics and anti-inflammatory medications to the site of the thrombus, respectively, to pursue a maximized combinational effect. Herein, we developed a probiotic-platelet hybrid vesicle-targeted drug delivery system (Fer-1@PLevs-C&U) to achieve sequential anti-thrombolytic delivery against thrombus and prevent its recurrence. The hybrid vesicles (PLevs) were prepared by mixing platelet membrane with Lactobacillus plantarum-derived bacterial extracellular vesicles (Levs) and further decorated with DSPE-PEG₂₀₀₀-CREKA, achieving “point-to-point” multi-covalent targeting of thrombus components. After targeted localization to the arterial thrombotic site, Fer-1@PLevs-C&U gradually releases the thrombolytic drug urokinase-type plasminogen activator (UPA) and Ferroptosis inhibitor (Fer-1) to facilitate thrombus dissolution and regulate the inflammatory microenvironment. By enhancing the eNOS expression and reducing the secretion of inflammatory factors TNF-α and IL-6, Fer-1@PLevs-C&U significantly reduced the inflammatory microenvironment and inhibited recurrent thrombus. Therefore, Fer-1@PLevs-C&U constitutes a novel biomimetic drug delivery platform with promising therapeutic potential and practical applicability.