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10.1016/j.jconrel.2021.05.035 http://scihub22266oqcxt.onion/10.1016/j.jconrel.2021.05.035 34058271!ä!34058271 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 261.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 261.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 261.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 261.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 294.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       J+Control+Release 2021 ; 335 (ä): 527-540 Nephropedia Template TP {{tp|p=34058271|t=2021. Systemic dendrimer nanotherapies for targeted suppression of choroidal inflammation and neovascularization in age-related macular degeneration |pdf=|usr=}}{{34058271}} gab.com Text Systemic dendrimer nanotherapies for targeted suppression of choroidal inflammation and neovascularization in age-related macular degeneration JO: J Control Release http://www.kidney.de/pget.php?&tw=1&pmid=34058271 #FOAvip Inflammation and neovascularization are key pathological events in human age-related macular degeneration (AMD). Activated microglia/macrophages (mi/ma) and retinal pigmented epithelium (RPE) play an active role in every stage of disease progression. Systemic therapies that can target these cells and address both inflammation and neovascularization will broaden the impact of existing therapies and potentially open new avenues for early AMD where there are no viable therapies. Utilizing a clinically relevant rat model of AMD that mirrors many aspects that of human AMD pathological events, we show that systemic hydroxyl-terminated polyamidoamine dendrimer-triamcinolone acetonide conjugate (D-TA) is selectively taken up by the injured mi/ma and RPE (without the need for targeting ligands). D-TA suppresses choroidal neovascularization significantly (by >80%, >50-fold better than free drug), attenuates inflammation in the choroid and retina, by limiting macrophage infiltration in the pathological area, significantly suppressing pro-inflammatory cytokines and pro-angiogenic factors, with minimal side effects to healthy ocular tissue and other organs. In ex vivo studies on human postmortem diabetic eyes, the dendrimer is also taken up into choroidal macrophages. These results suggest that the systemic hydroxyl dendrimer-drugs can offer new avenues for therapies in treating early/dry AMD and late/neovascular AMD alone, or in combination with current anti-VEGF therapies. This hydroxyl dendrimer platform but conjugated to a different drug is undergoing clinical trials for severe COVID-19, potentially paving the way for faster clinical translation of similar compounds for ocular and retinal disorders. Twit Text FOAVip Systemic dendrimer nanotherapies for targeted suppression of choroidal inflammation and neovascularization in age-related macular degeneration ????J Control Release http://www.kidney.de/pget.php?&tw=1&pmid=34058271 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=34058271 #FOAvip English Wikipedia <ref>{{Cite pmid|34058271}}</ref> Systemic dendrimer nanotherapies for targeted suppression of choroidal inflammation and neovascularization in age-related macular degeneration #MMPMID34058271 Kambhampati SP; Bhutto IA; Wu T; Ho K; McLeod DS; Lutty GA; Kannan RM J Control Release 2021[Jul]; 335 (ä): 527-540 PMID34058271show ga Inflammation and neovascularization are key pathological events in human age-related macular degeneration (AMD). Activated microglia/macrophages (mi/ma) and retinal pigmented epithelium (RPE) play an active role in every stage of disease progression. Systemic therapies that can target these cells and address both inflammation and neovascularization will broaden the impact of existing therapies and potentially open new avenues for early AMD where there are no viable therapies. Utilizing a clinically relevant rat model of AMD that mirrors many aspects that of human AMD pathological events, we show that systemic hydroxyl-terminated polyamidoamine dendrimer-triamcinolone acetonide conjugate (D-TA) is selectively taken up by the injured mi/ma and RPE (without the need for targeting ligands). D-TA suppresses choroidal neovascularization significantly (by >80%, >50-fold better than free drug), attenuates inflammation in the choroid and retina, by limiting macrophage infiltration in the pathological area, significantly suppressing pro-inflammatory cytokines and pro-angiogenic factors, with minimal side effects to healthy ocular tissue and other organs. In ex vivo studies on human postmortem diabetic eyes, the dendrimer is also taken up into choroidal macrophages. These results suggest that the systemic hydroxyl dendrimer-drugs can offer new avenues for therapies in treating early/dry AMD and late/neovascular AMD alone, or in combination with current anti-VEGF therapies. This hydroxyl dendrimer platform but conjugated to a different drug is undergoing clinical trials for severe COVID-19, potentially paving the way for faster clinical translation of similar compounds for ocular and retinal disorders. |*COVID-19[MESH] |*Dendrimers[MESH] |*Wet Macular Degeneration[MESH] |Angiogenesis Inhibitors[MESH] |Animals[MESH] |Choroid[MESH] |Humans[MESH] |Inflammation/drug therapy[MESH] |Rats[MESH] |SARS-CoV-2[MESH] |Vascular Endothelial Growth Factor A[MESH]Systemic dendrimer nanotherapies for targeted suppression of choroidal(epmc).pdf DeepDyve Pubget Overpricing