Nanoparticulate drug delivery systems (nDDS) offer a variety of options when it comes to routes of administration. One possible path is crossing mucosal barriers, such as in the airways and in the GI tract, for systemic distribution or local treatment. The main challenge with this administration route is that the size and surface properties of the nanoparticles, as opposed to small molecular drugs, very often results in mucosal capture, immobilization and removal, which in turn results in a very low bioavailability. Strategies to overcome this challenge do exist, like surface ‘stealth’ modification with PEG. Here we review an alternative or supplemental strategy, co-association of mucus modulating agents with the nDDS to improve bioavailability, where the nDDS may be surface modified or unmodified. This contribution presents some examples on how possible co-association systems may be achieved, using currently marketed mucolytic drugs, alternative formulations or novel agents.
It should be evident from the present review that mucus and mucus modifications are very complex areas where manipulation of one barrier more often than not will lead to a change in another barrier function because their highly interlinked nature. On top of that, not all barrier modulation strategies are universally applicable as different mucosal surfaces will provide different challenges (e.g. airway mucus vs. intestinal mucus). At the same time we also hope it has become clear that the overall mucus barrier to nanoparticles can, at least in theory, be modified by co-administration or co-formulation with modulating agents. If such systems will reach a practical/clinical level depends largely on the complexity of the formulation, and hence the probability of a feasible industrial production. Mucus modulation strategies are likely to be most applicable to application where the mucus is already abnormal, where stealth modifications of nanoparticles are difficult from a production point of view or in combination with stealth modifications for optimal uptake of for example extremely costly therapies.
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