Zwitterionic unimolecular bottlebrushes for mucosal transport

Mucus is a viscoelastic and adhesive gel that protect organs from allergens, bacteria, and viruses. On the other hand, it also acts as an obstacle to effective mucosal drug delivery. Particles targeted to specific sites can be efficiently trapped and removed by mucus, thereby limiting the effectiveness of drug delivery. Recent studies have observed higher diffusivity of rodlike particle leading to deeper mucus penetration than that of spherical ones with equivalent surface chemistry. Therefore, we discuss the use of rod-like unimolecular bottlebrushes and evaluate the effects of shape, size, surface chemistry, and rigidity for mucosal transport. Our strategy for generating mucopenetrating polymers is by using functionalized zwitterionic bottlebrushes copolymers. We will discuss the effects of backbone length, grafted side-chain length, backbone rigidity, and surface functionalization on transport. Analysis of bottlebrush copolymers’ properties were done by DLS, AFM, SAXS, TIRF (Total Internal Reflection), and confocal microscopy. The effects of the molecular properties of these bottlebrushes on their transport through mucus was evaluated using MUC5AC samples.