Lecture 16 Intracellular drug delivery.pdf

文档介绍：Molecular Principles of Biomaterials Spring 2003
Lecture 16: Intracellular drug delivery
Last time: nano- and micro-particle drug carriers
Delivery to tissues from systemic circulation
Today: Intracellular drug delivery
Reading: . Hoffman et al., ‘Design of “smart” polymers that can direct intracellular drug
delivery,’ Polym. Adv. Technol. 13, 992-999 (2002)
Ph gradients and drug delivery: cancer res. 56, 1194 (1996); adv drug deliv rev 25, 3(1997); see asokan minireview J.
Pharm. Sci 2002
Intracellular delivery of molecules
Pathways of import into the cell
ƒ Uptake of extracellular material by cells
o Endocytosis
ƒ Size limitations: ~500 nm or less
ƒ Occurs in clathrin-coated pits
ƒ Can be triggered by receptor binding
ƒ Environment within endocytic vesicles:
x PH lowered in pathway
Compartment Approximate pH Contents relevant for therapeutic delivery
Extracellular fluid DNAses, proteases, peptidases
Endosomes ~- Proteases
lysosomes ~- Proteases (. cathepsins)
cytosol
o macropinocytosis, phagocytosis
ƒ Specialized scavengers (macrophages, neutrophils) and antigen presenting cells
ƒ Size limitations: up to the size of the cell
Lecture 16 – intracellular delivery 1 of 8
Molecular Principles of Biomaterials Spring 2003
Endocytosis:
(nearly all cells)