Title : Nanoparticles in receptor-mediated drug delivery to brain parenchyma
Abstract:
In RMT route, NPs are designed to target specific cells and cause cell death or induce a significant change in cellular behavior. Receptor?targeted therapeutics are developed to restrict the distribution of toxic drugs to only the pathologic cells, thus diminishing collateral side effects to healthy ones. Note worthly, receptor?mediated drug delivery by NPs not only can enable membrane?impermeable drugs to enter target cells by receptor?mediated endocytosis, but it can induce remarkable changes in cell fate by activating a receptor’s natural signaling cascade. Endocytosis encompass the route by which extracellular substrate is carried into a cell by membrane invagination. Almost all eukaryotic cells experience endocytosis, and can take part in processes as hormone signaling , vitamin and mineral uptake, extracellular solute uptake, pathogen removal, and even simple membrane turnover. Indeed, endocytosis is an active phenomenon in some cells that the entire plasma membrane is internalized and replaced in less than 30 minutes. Three sub categories are considerable in endocytosis process which include Phagocytosis, Fluid-phase pinocytosis and receptor?mediated endocytosis. Receptors belong to a class of proteins with extracellular domain which interact to specific exogenous ligand and carry the receptor/ligand (R/L) complex in to the cell by vesiculation. Interestingly, some specific receptors overexpressed under pathological condition which can be exploited for targeted drug delivery by NPs, e.g. diphtheria toxin receptor in inflammatory disease. RMT pathway also known as the molecular Trojan horse strategy due to its capability in transporting of ligand associated cargoes. Endocytosis after ligand/receptor complex formation which follow by transport through endothelial cytoplasm and exocytosis at basolateral side of the BBB are the three important steps of the RMT. Nanoparticles as drug or drug vehicles may be threatened by degradation in second step due to lysosomal system which isn’t considerable in brain drug delivery. Over all, RMT route is so considerable to drug delivery by nanoparticles due to low side effect and targeted drug delivery.
Audience take away:
- Advantages and disadvantage of nanoparticles as drug or drug delivery vehicles (DDV)
- Importance of Drug delivery to central nerve system
- RMT route to cross the Blood-Brain Barrier (BBB)
- RMT importance in CNS drug delivery
