The eye is a complex structure with a variety of anatomical barriers and clearance mechanisms, so the provision of safe and effective ophthalmic drug delivery technology is a major challenge.
Myocardial infarction (MI) has become one of the serious diseases threatening human life and health. However, traditional treatment methods for MI have some limitations, such as irreversible myocardial necrosis and cardiac dysfunction. Fortunately, recent endeavors have shown that hydrogel materials can effectively prevent negative remodeling of the heart and improve the heart function and long-term prognosis of patients with MI due to their good biocompatibility, mechanical properties, and electrical conductivity. Therefore, this review aims to summarize the research progress of injectable hydrogel in the treatment of MI in recent years and to introduce the rational design of injectable hydrogels in myocardial repair. Finally, the potential challenges and perspectives of injectable hydrogel in this field will be discussed, in order to provide theoretical guidance for the development of new and effective treatment strategies for MI.
A typical prescription of traditional Chinese medicine (TCM) contains up to a few hundreds of prototype components. Studying their absorption, metabolism, distribution and elimination (ADME) represents great challenges. The objective of this study was to develop a practical approach for investigating ADME of individual prototypes in TCM. An active fraction of Xiao-Xu-Ming Decoction (AF-XXMD) as a model TCM prescription was orally administered to rats. AF-XXMD-related components in plasma, urine, bile and feces were detected using high resolution mass spectrometry and background subtraction, an untargeted data-mining tool, and structurally characterized based on MSn spectral data. Connection of detected AF-XXMD metabolites to their precursor species, either prototypes or upstream metabolites, were determined based on mass spectral similarity and the matching of biotransformation reactions. As a result, 247 AF-XXMD-related components were detected and structurally characterized in rats, 134 of which were metabolites. Among 198 AF-XXMD prototypes dosed, 65 were fully or partially absorbed and 13 prototypes and 34 metabolites were found in the circulation. Glucuronidation, isomerization and deglycosylation followed by biliary and urinary excretions and direct elimination of prototypes via kidney and liver were major clearance pathways of AF-XXMD prototypes. As an example, the ADME profile of H56, the single major AF-XXMD component in rat plasma, was elucidated based on profiles of H56-related components in plasma and excreta. The results demonstrate that the new analytical approach is a useful tool for rapid and comprehensive detection and characterization of TCM components in biological matrix and study of ADME of a TCM prescription in vivo.
Reducing L‐lactate levels in tumors is crucial for alleviating immunosuppression and enhancing treatment efficacy. Recently, bacteria have great potential in improving lactate levels in the tumor microenvironment due to their physiological properties, tumor tropism, and immunogenicity. However, developing bacterial‐based lactate regulation platforms is still facing great challenges due to bacterial modification impacts on activity, macrophage phagocytosis, and complex tumor microenvironment. Herein, an engineered Lactobacillus acidophilus (LH@LA) is developed, armed with a polymeric stealth coating that co‐loads lactate oxidase (LOx) and horseradish peroxidase (HRP). This coating protects bacteria from macrophage phagocytosis, maintaining their activity for deep tumor drug delivery. And then, LOx and HRP can consume much L‐lactate in the tumor site through an enzyme cascade reaction to improve the immunosuppressive environment, while causing oxidative stress and reduced ATP supply, thereby reversing AKT‐mTOR metabolic pathway activation to inhibit tumor growth. More interestingly, LA not only acts as a natural enzyme's carrier, but also induces anti‐inflammatory M2 macrophages to polarize into pro‐inflammatory M1 macrophages by secreting D‐lactate, enhancing antitumor immunotherapy. This engineered probiotic design provides a new idea for building a safe and efficient live bacteria delivery platform, providing a reference for developing cancer treatment strategies with clinical translation prospects.
7 January 2022 in Journal of Pharmaceutical and Biomedical Analysis