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Nanoparticles for Cardiovascular Medicine: Trends in Myocardial Infarction Therapy
Published in Harishkumar Madhyastha, Durgesh Nandini Chauhan, Nanopharmaceuticals in Regenerative Medicine, 2022
Fujiwara et al. also targeted the inflammatory response in MI injury using PLGA nanoparticles (Fujiwara et al. 2019). The researchers loaded PLGA with TAK-242, a toll-like receptor 4 (TLR4) inhibitor. TAK-242-loaded PLGA nanoparticles attenuated MI through targeting monocytes/macrophages present within the spleen, blood, and heart. The nanoparticles inhibited Ly-6Chigh monocytes recruitment to infarcts but did not affect infarct size in TLR4/CCR2-deficient mice, indicating a TLR4-specific mechanism and monocyte/macrophage-mediated inflammation were primary therapeutic targets of TAK-242-PLGA nanoparticles in regulating MI in mice. Tokutome et al. focused on peroxisome proliferator-activated receptor-γ (PPARγ) (Tokutome et al. 2019). Binding of pioglitazone to PPARγ induces receptor heterodimerisation with retinoid X receptor (RXR). The PPARγ/RXR heterodimer complex binds PPAR response elements to regulate gene expression associated with adipogenesis, lipid/glucose metabolism (Ahmadian et al. 2013; Libby and Plutzky 2007), chemokine expression, and macrophage infiltration (Ricote and Glass 2007). In monocytes/macrophages, PPARγ activation drives pro-healing M2 polarisation of macrophages (Odegaard et al. 2007). Pioglitazone administered orally before I/R reduced infarct size in mouse and rat MI models (Ye et al. 2008); however, intraperitoneal injection of pioglitazone at the time of reperfusion resulted in lost effect (Honda et al. 2008). Cardioprotective agents are typically administered during reperfusion. Tokutome et al. determined that it was essential to use a carrier to facilitate pioglitazone delivery to effector cells in I/R injury (Tokutome et al. 2019). In lieu of reports that PLGA nanoparticles accumulate in I/R myocardium and were taken up by circulating macrophages (Nagaoka et al. 2015; Gustafson et al. 2015), researchers developed PLGA nanoparticles as carriers for pioglitazone and showed that they exerted an antiinflammatory effect, which in turn limited the infarct size in I/R mouse and porcine models. The rationale to target PPARγ was supported by the work of Nakano et al., which employed irbesartan as a therapeutic agent for MI (Nakano et al. 2016). Irbesartan blocks angiotensin II type 1 receptor and conveys a partial agonistic effect on PPARγ, and an irbesartan derivative was shown to reduce myocardial inflammation by reducing proinflammatory cytokine expression by cardiomyocytes after MI and conveyed an antihypertensive effect (Ugdutt et al. 2010). Thus, Nakano et al. developed PLGA nanoparticle-mediated delivery of irbesartan, which accumulated at the MI site when administered intravenously at the time of reperfusion, where the enhanced permeability and retention effect improved vascular permeability (Acharya and Sahoo 2011) and subsequently allowed nanoparticles to be rapidly taken up by mononuclear and phagocytic cells that had infiltrated the MI site. The mechanism of action was shown to be through irbesartan antagonising the additional recruitment of Ly6ChighCCR2+ inflammatory monocytes into the MI site.
Transformation of PPCPs in the environment: Review of knowledge and classification of pathways according to parent molecule structures
Published in Critical Reviews in Environmental Science and Technology, 2023
Kevin Bonnot, Pierre Benoit, Laure Mamy, Dominique Patureau
The Cluster 4 was the one with the highest number of molecules (34), but which were poorly discriminated by specific characteristics (Table S5, supplementary material). The main fragments or descriptors were aliphatic or aromatic carbon chains that were also present in all clusters. This group gathered compounds of several use families: six of the seven NSAID molecules, bisphenol A and tetrabromobisphenol A, antihypertensives (irbesartan and valsartan), and the antimicrobials triclosan and triclocarban.