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Mucus as a Barrier for Biopharmaceuticals and Drug Delivery Systems

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Mucosal Delivery of Biopharmaceuticals

Abstract

Over the past few decades, mucosal drug delivery systems have received great attention in the literature. Mucus is a complex system that lubricates and protects the biological barriers such as the human lungs, gastrointestinal tract, vagina, and the eyes. It also serves as a physical selective barrier allowing the rapid passage of small (e.g., ions) and relatively large molecules (e.g., proteins), and blocking many others (e.g., pathogens and ultrafine particles). The unique rheological and adhesive properties of mucus protect the epithelium from both mechanical forces and foreign pathogens and particles, leading to a rapid mucus secretion and clearance rate which limit the residence time of administered biopharmaceuticals and drug delivery systems. Thus, dosage forms are designed with mucoadhesion properties in order to adhere to mucosal membranes to enable prolonged retention time at the site of absorption, control the drug release, and increase the drug plasma concentrations and the therapeutic activity. The mucoadhesive ability of the dosage forms depends on various factors, including the nature of the mucosal tissue and the physicochemical properties of the polymeric formulation. In this chapter, we start by briefly introducing some of the important properties of mucus and mucosal membranes that need to be overcome in drug delivery applications. We then address some of the roles of mucus in blocking nanoparticulate drug delivery systems. We further highlight the mucoadhesive properties of particulates, the design and development of mucus-penetrating delivery systems to avoid rapid mucus clearance and to provide targeted or sustained drug delivery for localized therapies in mucosal tissues (e.g., buccal, nasal, ocular, gastro, vaginal, and rectal). Next, we also present an example of mucus-penetrating particles used to target a disease state mucosa. Finally, we conclude the chapter with a brief overview of our visions of the future of mucoadhesive drug delivery systems and their potential to overcome the mucus limitations in drug delivery.

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Acknowledgments

Hélder A. Santos acknowledges the Academy of Finland (projects numbers 252215 and 256394), the University of Helsinki, and the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007–2013)/ERC Grant agreement number 310892 for financial support.

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  1. Division of Pharmaceutical Technology, Faculty of Pharmacy, University of Helsinki, FI-00014, Helsinki, Finland

    Hongbo Zhang, Mohammed-Ali Shahbazi, Patrick V. Almeida & Hélder A. Santos

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  1. IINFACTS - Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Instituto Superior de Ciências da Saúde-Norte, CESPU, Gandra, Portugal

    José das Neves

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Zhang, H., Shahbazi, MA., Almeida, P., Santos, H. (2014). Mucus as a Barrier for Biopharmaceuticals and Drug Delivery Systems. In: das Neves, J., Sarmento, B. (eds) Mucosal Delivery of Biopharmaceuticals. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-9524-6_3

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