Biology of Drug Delivery

ndifranco94's version from 2015-11-03 19:55


Question Answer
Challenges in DDPoor solubility, Instability, Unfavorable pharmacokinetics, Low targeting efficacy, Toxicity, Low therapetic index
Barriers for in vivo delivery of cancer drugsnon-specific uptake, endothelium of blood vessels (BBB), rapid renal clearance, cell membrane, lysosomal degradation, intracellular drug release, nuclear membrane
Two strategies for delivering drug to tumorpassive and active targeting
Passive targetingUtilizes the hyperpermeability of tumor vasculature for enhanced permeation and retention effect (EPR)
Active targetingTarget-specific binding to the diesase-releated biomarkers on the cell surface of dieased tissue, receptor-mediated DD
DD Systemcarrier, therapetic agent, target-finding agent (sometimes)
Drug carrierswater soluble polymers, polymeric micelles, polymeric spheres, liposomes
Potential advantages of drug deliveryoptimized pharmacokinetics, reduced systemic toxic side effects, increase bioavilability w/ decreased dosages, improved stability, increased aqueous solubility, enhanced therapeutic efficacy
MW of tumor drugshigher MW = higher accumulation at the tumor
EPRpermeability b/c of leaky vasculature, retention b/c of compromised lymphatic drainage
FActors on the EPR Effectsize-dependent, controlled by renal filtration threshold, heterogenous in solid tumors, affected by charge and lipophilicity, stroma may impede transport, affected by vascular mediators s/a bradykinin, NO, prostaglandins, angiotensin-converting enzyme inhibitors, VEGF
Phagocytosisopsonization of the particles by opsonins, binding to the membrane of phagocytes, engulfment, merge w/ lysosomes
PinocytosisClathrin-mediated endocytosis or non-clathrin-mediated endocytosis
Clathrinfibrous protein w/ three-limbed triskelion, which polymerizes into a lattice along the membrane and causes endocystosis
Caveolae-mediate dendocystosisCaveolae (small dents in membrane) formed by caveolin, receptor independent endocytosis
Macropinocytosiss/a caveolae-mediated endocytosis except larger dents
Receptor-mediated endocytosisspecific binding, internalization, release of therapeutics in cytosol

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