FIGURE 6.

Synthesis and antiangiogenic effects of Sn2 lipase-liable prodrug micelles for the treatment of asthma. (a) Synthesis of fumagillin PAzPC prodrug and through saponification and esterification alongside structure of α_Vβ₃-peptidomimetic-PEG₂₀₀₀-PE. (b) Synthesis of docetaxel prodrug. (c) i) 19F/1H magneitc resonance (MR) tomographic molecular imaging following antiangiogenesis treatment in HDM rats with α_Vβ₃-Dxtl-PD micelles (right) revealed markedly reduced airway neovascular MR signal when compared to the control asthmatic animals receiving α_Vβ₃-empty micelles (left). ii) Normalized lung signal quantification of 19F/1H MR tomographic molecular imaging (*p < 0.01). (d) Histogram of 19F/1H MR tomographic molecular imaging results showing equivalent reduction in neovascularity with anti-angiogenesis micelles. (e) Pulmonary functional changes in HDM rats receiving α_Vβ₃-Dxtl-PD, α_Vβ₃-Fum-PD, or α_Vβ₃-no-drug micelles. i) Respiratory system resistance (Rrs) was measured after increasing methacholine (MCh) concentrations showing attenuated reactivity among rats treated with α_Vβ₃-Dxtl-PD or α_Vβ₃-Fum-PD micelles(***p < 0.001). ii) Respiratory system compliance (Crs) in HDM rats following the MCh challenge showing greater compliance after the treatment with drug-loaded micelles (***p < 0.001). (f) Bronchoalveolar (BAL) cell profiles showing a lower percentage of eosinophils (EOS) in HDM rats receiving α_Vβ₃-Dxtl-PD and α_Vβ₃-Fum-PD micelles (left) and flow cytometry of BAL fluid (right) revealing that α_Vβ₃-Fum-PD and α_Vβ₃-Dxtl-PD micelles decreased α_Vβ₃+ macrophage/monocyte numbers versus empty micelles(*p < 0.05, ***p < 0.001). (Reprinted with permission from Lanza et al. (2017). Copyright 2017 Ivyspring International Publisher)