The development of transmucosal delivery strategies is hampered by the complex and dynamic nature of the mucosal barrier. Successful mucopenetrating strategies suggest the importance of a balance between mucoadhesive and mucorepulsive characters. Two parameters only recently explored for mucus transport are particle shape and stiffness. While particle morphology has been extensively studied to explain particle-cell interactions, there is little information on its influence on mucopenetration, despite the fact that most bacteria have rodlike morphologies and exhibit high mobilities in mucus. The majority of studies examining particle shape in mucopenetration have focused on stiff nanorods, including mesoporous silica and polystyrene. However, recent studies have found that nanoparticle flexibility also influences mucopenetration. Herein, we will discuss the effects of the structural parameters of macromolecular bottlebrushes, including backbone and side-chain lengths, bottlebrush rigidity, and terminal group chemistry, on their ability to penetrate mucus. We evaluate the effect of bottlebrush nanoparticle morphology and chemistry on their stability and dilute solution interactions with mucus by light scattering methods, and examine their diffusivity by fluorescence recovery after photobleaching. Structure-property relationships will be discussed for bottlebrushes of (poly(2-methacryloyl oxyethylphosphorylcholine)) and poly(carboxybetaine).

Zwitterionic bottlebrushes as mucopenetrants

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ACS Fall 2022

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