Biological Barriers: Transdermal, Oral, Mucosal, Blood Brain Barrier, and the Blood Eye Barrier
Compartmentalisation is a precondition for the development of life, allowing concentration gradients to be maintained, facilitating selective transport of molecules, functional polarisation, protection of cells and tissues. Consequently, organisms have ev
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Biological Barriers: Transdermal, Oral, Mucosal, Blood Brain Barrier, and the Blood Eye Barrier Preethi Marimuthu and Andreas G. Schätzlein
Abstract Compartmentalisation is a precondition for the development of life, allowing concentration gradients to be maintained, facilitating selective transport of molecules, functional polarisation, protection of cells and tissues. Consequently, organisms have evolved highly sophisticated structures and mechanisms that allow compartmentalisation to be maintained and controlled in a highly regulated fashion. Under normal conditions these compartmentalising structures are essential building blocks of life, their smooth functioning being central to our health. However, the same effectiveness that is a bonus under physiological conditions means the same structures may become considerable barriers to the pharmacotherapy of diseases, as access of drugs to the sites of disease may be severely restricted. This chapter describes the architecture, organisation, and function of key barriers that therapeutic nanoparticles may encounter for the most important routes of drug administration. The epithelial barriers (skin, mucosa of the airways, and gastrointestinal tract) and endothelial barriers share many commonalities as they all share key design elements that have evolved to support compartmentalisation.
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Introduction
A key biological principle is organisation by compartmentalisation. This approach is key to creating defined environments within which conditions can be finely controlled and tuned. This is a common principle shared by all living organisms from
P. Marimuthu Department of Pharmaceutics and Biochemistry, University of London School of Pharmacy, London, UK A.G. Schätzlein (*) UCL School of Pharmacy, University College London, 29 - 39 Brunswick Square, London WC1N 1AX, UK e-mail: [email protected] I.F. Uchegbu et al. (eds.), Fundamentals of Pharmaceutical Nanoscience, DOI 10.1007/978-1-4614-9164-4_12, © Springer Science+Business Media New York 2013
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P. Marimuthu and A.G. Schätzlein
Fig. 12.1 The organisation of barriers in the body. The compartmental organisation of the human body defines barriers for drug delivery at the body, organ, and cellular level. Epithelial tissues control access from the environment to the systemic blood circulation from where distribution occurs throughout the body (orange bars). The vessel walls and specifically the endothelial cells control access from the systemic circulation to the organs and their interstitial tissue (yellow bars). At the cellular level uptake is controlled at the surface and by surface membrane-derived organelles (endocytosis) as well as between the cytoplasm and various intracellular organelles (magenta bars)
microorganisms to plants and animals. All organisms that are metabolically active and have the ability to grow and multiply exist in a dynamic equilibrium with their environment to allow exchange of nutrients, waste products, and information. These requirements have led to the evolution of a soph
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