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Transcript of Liposomes
Blood Brain Barrier
Higher Dosages Required
Non-Specific (Side) Effects Boron Trifluoride Dihydrogen Monoxide (Potentially lethal) POLARITY The Partition Coefficient PHARMACOLOGY PHARMACOKINETICS You = Nonlinear Complex System Targeting + Lower Dosage
= Fewer Side Effects Memorize by Friday. Next Generation Smart Drugs PHARMACODYNAMICS In-Silico Modeling Affinity = Shape of Key Efficacy = Torque in Keyhole TI = ED / TD High Therapeutic Index = Great Success Agonist vs. Antagonist
(Morphine vs. Naloxone) Dissolve lipid insoluble compounds through fat
Slowly leak payload (infrequent administation)
Conjugate with antibodies and aptamers
Polyethylene glycol coat for immuno-cloaking Liposome = Evolved Form of Micelle Multi-Lamellar Vesicles O SNAP! Fractal Hydro-philic/phobic Sandwich Electron Micrograph Torchilin, Vladimir P. Recent Advances with Liposomes as Pharmaceutical Carriers. 2005. Nature Reviews Drug Delivery. In the "real world" (?) How To Yield Smaller Liposomes Usually between 20 and 200 nm, 1 nm = one millionth of a milimeter Sonicator "Pressure Extrusion" = Filter Emerging Methods Lyophilize and Aerosolize
Artificial Blood (Haemosomes)
Vaccines and Virosomes Paraquat Tested PQ-protective effect of NAC and L-NAC on A549 lung adenocarcinoma cells. Most prevalent herbicide -- very nasty, linked to Parkinson's. Powerful ROS generator. Very bad for farm workers who spray by hand. The primary non-enzyme antioxidant / free radical scavenger due to thiol (sulfur containing) group.
Low GSH = all cause mortality + cellular age. Rate-limiting precursor to de novo GSH synthesis, antioxidant in its own right.
Influences important cell signalling pathways, particularly as an anti-inflammatory.
Shown to promote cell growth and survival. Results Uptake Viability
Torchilin, V. Recent Advances with Liposomes as Pharmaceutical Carriers. 2005. Nature Reviews Drug Delivery.
Mitsopoulos P. and Suntres Z. Protective Effects of Liposomal N-Acetylcysteine Against Paraquat-Induced Cytotoxicity and Gene Expression. 2011. Journal of Toxicology.
Papahadopoulos, D. Liposomes and their use in biology and medicine. 1978. New York Academy of Science.
Sharma A. and Sharma U. Liposomes for Drug Delivery: Progress and Limitations. 1997. International Journal of Pharmaceutics.
Lasic, D. Liposomes: From Physics to Applications. 1993. Elsevier, Amsterdam. Thank You For Listening Sources: Discovery Haematologist Alec Bangham (1964) at Cambridge. Using newfangled "Electron Microscope." Pressure and Tension Laplace's Law The larger the vessel radius, the greater the wall tension required to withstand internal fluid pressure (force over area, where force is enthalpy times the number of molecules). Adding cholesterol Liposomes can be stabilized by: Longer chain fatty acids More branch chained fatty acids (unsaturated). Butter vs. olive oil. Hydrophilic Hydrophobic