Drug targeting Flashcards
What are the number of problems that are associated with the conventional therapy
that lead to sub- optimal treatment - 4
Non specific distribution of drug throughout the body,Lack of drug selectivity for specific pathological sites,Large total dose of drug required but low dose at site required,non specific toxicity and other adverse effects.
Drug targeting is what?
The ability of the drug to accumulate in the target organ or tissue selectively independent of the site or method of administration.
What is passive targeting and give an example:
Nanoscae drug delivery systems can increase the concentration of drug at the site of action through passive or active targeting. They also decrease drug concentration in normal non diseased tissue to reduce toxic effects and they improve pharmaco kinetic and dynamic profiles.- To achieve this minimum amounts of drugs should be released during transit and as much as possible should be released at targeted site.
What are nano -particles?
solid spherical – 100nm in size with drug in polymer matrix
What are nano – Capsules?
Drug entrapped in a cavity surrounded by a polymer membrane
What are polymeric micelles?
spheroidal structures with hydrophobic core which increase solubility of poor- water soluable drugs and hydrophilic corna which allows a long circulation time and prevents interactions between core and blood.Dynamic structure – 50 nm
What are liposomes?
Closed spherical vesicles formed by one or more phospholipid bilayers around an aqueous core in which the drug is entrapped.
What happens with any foreign particle that enters the body?
iposme encounters multiple defense mechanisms aimed at recognition,neutralisation and elimination of invading substance
What is the relevance of the RES and what does it stand for specifically?
reticuloendothelial system – important component of the immune system. It comprises phagocyte cells found in various organs of the human body.They are located in reticulum connective tissue,upon leaving the circulatory sytem they become Macrophages – Macrophages. Macrophages will readily take up and phagocytose liposomes.
What is doxorubicin given using? And how does that help?
using stealth liposomes (>90% of doxorubicin is encapsulated).Stealth liposomes are protected from detection by the mononuclear phagocyte system because they are coated using surface bound methoxy PEG.This increases blood circulation time and increases the chance of being taken up by tumour cells. DXR is also less cardiotoxic,myelotoxic and nephrotoxic in this formulation because distribution is altered.
What is the process involving the growth of new blood cells?
Angigogenesis from pre – existing vessels.This occurs when tumour exceeds 2mm.
What is active targeting?
A ligand attatched at a surface of a nanocarrier for binding to appropriate receptors at target site.The ligan may allow the drug to attatch itself to the surface of the cell or internalise for intracellular drug release- FORMATION IS CALLED LIGAND PEGYLATED NANOPARTICLE
What are the 3 aims of targeting cancer cells?
To improve cellular uptake of therapeutic macromolecular drugs, to target surface receptors over expressed by cancer cells only, to target receptors that are likely to be internalised such as egfr
What else other than cancer cells are targeted?
Tumour endothelial cells – not cancer cells!!!! Aim is to destrog angiogenic blood vessles and kill tumour by depriving them of oxygen and nutrients.
Defective blood vessels
Defective blood vessels have sacs-like formations and festerations which have enhanced permeiablility and retention. This is enhanced permeability for drugs/carriers to move from microcapillaries to interstitium surrounding tumour cells and lack lymphatic drainage.- so drugs are retained in the tumour interstitium.Drugs should be less tha n10 nm to avoid filtration by the kidney and more than 100 nm to avoid capture by liver and should beneutral or anionic to avoid renal elimination.
