Dual pancreas- and lung-targeting therapy for local and systemic complications of acute pancreatitis mediated by a phenolic propanediamine moiety

Abstract

To inhibit both the local and systemic complications with acute pancreatitis, an effective therapy requires a drug delivery system that can efficiently overcome the blood-pancreas barrier while achieving lung-specific accumulation. Here, we report the first dual pancreas- and lung-targeting therapeutic strategy mediated by a phenolic propanediamine moiety for the treatment of acute pancreatitis. Using the proposed dual-targeting ligand, an anti-inflammatory compound Rhein has been tailored to preferentially accumulate in the pancreas and lungs with rapid distribution kinetics, excellent tissue-penetrating properties and minimum toxicity. Accordingly, the drug-ligand conjugate remarkably downregulated the proinflammatory cytokines in the target organs thus effectively inhibiting local pancreatic and systemic inflammation in rats. The dual-specific targeting therapeutic strategy may help pave the way for targeted drug delivery to treat complicated inflammatory diseases.

Keywords: 3-propane diamine; Acute pancreatitis; Dual specific-targeting; N,N,N′-trimethyl-N′-(4-hydroxy-3-methyl-benzyl)-1; Rhein; Systemic complication.