PLA-PEG-Mal used for macrophage targeting as colitis treatment

PolySciTech (www.polyscitech.com) provides a wide array of maleimide endcapped copolymers including PLGA-PEG-maleimide and PLA-PEG-mal. Recently these types of polymers have been utilized to generate an antibody fragment labelled nanoparticle for delivery of SiRNA to macrophages to treat colitis. This raises the potential for an oral treatment of inflammatory bowel disease (IBD) with minimal side effects. Read more:  Laroui, Hamed, Emilie Viennois, Bo Xiao, Brandon SB Canup, Duke Geem, Timothy L. Denning, and Didier Merlin. "Fab'-bearing siRNA TNFα-loaded nanoparticles targeted to colonic macrophages offer an effective therapy for experimental colitis." Journal of Controlled Release 186 (2014): 41-53. http://www.sciencedirect.com/science/article/pii/S016836591400279X

“Abstract: Patients suffering from inflammatory bowel disease (IBD) are currently treated by systemic drugs that can have significant side effects. Thus, it would be highly desirable to target TNFα siRNA (a therapeutic molecule) to the inflamed tissue. Here, we demonstrate that TNFα siRNA can be efficiently loaded into nanoparticles (NPs) made of poly (lactic acid) poly (ethylene glycol) block copolymer (PLA–PEG), and that grafting of the Fab' portion of the F4/80 Ab (Fab'-bearing) onto the NP surface via maleimide/thiol group-mediated covalent bonding improves the macrophage (MP)-targeting kinetics of the NPs to RAW264.7 cells in vitro. Direct binding was shown between MPs and the Fab'-bearing NPs. Next, we orally administered hydrogel (chitosan/alginate)-encapsulated Fab'-bearing TNFα-siRNA-loaded NPs to 3% dextran sodium sulfate (DSS)-treated mice and investigated the therapeutic effect on colitis. In vivo, the release of TNFα-siRNA-loaded NPs into the mouse colon attenuated colitis more efficiently when the NPs were covered with Fab'-bearing, compared to uncovered NPs. All DSS-induced parameters of colonic inflammation (e.g., weight loss, myeloperoxidase activity, and Iκbα accumulation) were more attenuated Fab'-bearing NPs loaded with TNFα siRNA than without the Fab'-bearing. Grafting the Fab'-bearing onto the NPs improved the kinetics of endocytosis as well as the MP-targeting ability, as indicated by flow cytometry. Collectively, our results show that Fab'-bearing PLA–PEG NPs are powerful and efficient nanosized tools for delivering siRNAs into colonic macrophages. Keywords: TNF secretion; Targeted siRNA release; DSS induced colitis; Ligand-mediated targeting”