Module 1-C Biological Barriers. Biological Barriers. DRUG. DRUG. Human barriers . Skin. Mucosa. PROBE. PROBE. External barriers . Cellular Delivery . En route barriers . Cellular barriers . Blood. Extracellular matrix. Endosomal / lysosomal degradation.
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En route barriers
to the targeted sub-cellular organelles
Common Routes of Administration
Human Barrier (Errors)
First Pass Mechanism
Metabolism occurs during the absorption process. The fraction of the initial dose appearing in the portal vein is the fraction absorbed, and the fraction reaching the blood circulation after the first-pass through the liver defines the bioavailability of the drug.
Histologic image of human epidermis
Source: Grays Anatomy
Composition of gastric mucus
Source: DOI: 10.5772/23951
Possible destabilization and degradation pathways of probes during in vivo circulation
Immunoglobulins, complement proteins, albumin,
apolipoprotein and fibrinogen.
adsorbs on the surface of nanoparticles and tag them for attack by the MPS.
Scavengers to engulf foreign particles
Blood Brain Barrier (BBB)
A cortical microvessel stained for blood-brain barrier protein ZO-1
Diffusion of Agents Through Cellular Bilayer
(a) ibuprofen, (b) aspirin, (c) erythromycin
Charged molecule: activity of specific transport and channel proteins
Can There be a Direct Access to the Cytoplasm?
How can we avoid endosomal escape pathway?
Cell Penetrating Peptides (CPPs)
1988 1994 1996 1997 2000 2001 2004 2006 2008
Extra Vascular NP: How Far Below We Could Drive the Size Down?
Co - Self-assembly
Kim, Lanza, Pan, Adv Health Mat 2012
Pan, Turner, WooleyMacromolecules, 2004, 37 (19), pp 7109–7115
Becker, Pan, Wooley Bioconjugate Chemistry 2003