Intracellular Delivery of Budesonide and Polydopamine Co-Loaded in Endosomolytic Poly(butyl methacrylate-co-methacrylic acid) Grafted Acetalated Dextran for Macrophage Phenotype Switch from M1 to M2

Abstract

In this study, a rationally designed nanocomposite (BUDPDA@MAP) composed of polydopamine (PDA) nanoparticle and anti-inflammatory drug budesonide (BUD) encapsulated in a pH-responsive endosomolytic polymer (poly(butyl methacrylate-co-methacrylic acid) grafted acetalated dextran, denoted by MAP), is proposed. The uniform nanocomposite is prepared using a microfluidic device. At low endosomal pH (5.5), MAP destabilizes the endosomal membranes for the cytoplasmic delivery of PDA, and releases BUD simultaneously, resulting in a greater reactive oxygen species scavenging capability than both the free drug and PDA alone. The combined therapeutic efficacy from PDA and BUD also leads to a successful macrophage phenotype switch from pro-inflammatory M1 to anti-inflammatory M2.