Current topics in drug discovery Flashcards
How do hydrolysis and oxidation affect liposome stability?
Hydrolysis leads to formation of lysolipids, highly regulated species.
Oxidation leads to formation of peroxide radicals, highly reactive species.
Both hydrolysis and oxidation destabilise liposomes and lead to their breakdown.
What can be done to change liposome composition and structure to improve stability?
Use of stealth liposomes: saturation avoids oxidation and reduces susceptibility to hydrolysis, PEGylation reduces access of water, improving half-life of liposomes in blood.
What is the composition of liposome formulations?
Stealth liposomes: an example is H-soyPC, cholesterol and DSPE-PEG. Drug enclosed in centre of liposome. H-soyPC is the saturated species, with DSPE-PEG used to improve solubility/impede water access. Cholesterol prevents hardening, allowing release of drug.
What is the composition of SLN formulations?
Solid lipid core surrounded by stabilising layer of surfactant.
What are the benefits of liposome and SLN formulations?
Large size allows for targeted build-up of drug in cancer cells, capillary windows large enough to allow through, not the case in most non-cancerous cells.
Liposomes: formulation of difficult drugs possible, with lots of off-target activity/poor solubility.
SLNs able to sequester more material with higher dosages with more complex cargos (e.g. mRNA).
What is an example of a drug-induced liver injury and what are the common features of drugs that may induce this type of problem?
Examples: steatosis (build up of fat in liver), drug induced phospholipidosis (build up of phospholipids in liver). Cationic amphiphilic drugs prone to inducing it. Amphiphilic = large hydrophobic and hydrophilic regions and cationic = net positive charge at physiological pH.
