Advanced Drug Delivery - WIP Flashcards
Routes of movement, delivery to brain
Describe the route of drug movement of ibuprofen
Ibuprofen, is coated. Goes to the stomach but not broken down due to coating. No irritation to the lining of stomach.
Goes to upper intestine. Intestine is a basic environment. The basic breaks the coating and the ibuprofen is released. Ibuprofen is absorbed in the villi.
It then gets absorbed from villi into hepatic portal vein.
It then go to liver for the 1st pass metabolism effect, Drug become polar.
Drug diffuse out of veins due to the pressure and gets into interstitial space. Its action will take place on receptors. For example, reduce the inflammation in knee.
Once undertaken its role, it then moves in lymphatic capillaries. Driving force is the fact that we are walking and moving about. As the muscles contract it pushes against the lymphatic system.
We must be physically active to have our lymphatic system working. Lymph is moving, the B and T cells are responding to what is moving
along. The contents is then passed into cardiovascular system through
thorocic duct. Then the content go into liver to become more polar, goes to kidney
and get excreted and move out of the body.
What is oedema?
Oedema is a build-up of fluid on the body which causes the affected tissue to become swollen. May be local or general depending on the cause
When the skin is pressed it does not come back to its original shape
What is the lymphatic system?
Made from capillaries similar to those in the circulatory system, but larger in diameter and with closed ends. Unlike blood capillaries, fluid can flow into lymph capillaries but cannot flow out through the cell walls
Fenestrated capillaries have pores which allow passage of proteins into the lymphatic system an control of fluid balance.
The lymph nodes contain T and B cells which respond to foreign materials
What are typical nanoparticle characteristics?
Size – range from 1-1000nm, lower sizes (20-200nm) are more likely to be absorbed efficiently through the intestinal lining
Surface properties – charge, hydrophobicity and functionalization affect how nanoparticles interact with biological tissues and influence cellular uptake
Materials – biodegradable and biocompatible materials (e.g. liposomes, polymeric nanoparticles, lipid-based nanoparticles) are preferred for oral delivery as they are less likely to cause toxicity and can be designed to release their payload in specific areas in the GI tract
What is controlled and sustained release?
Surface modifications (e.g. antibodies or ligands that bind to specific receptors) can be used to engineer nanoparticles to target specific cells or tissues, such as cancer cells, immune cells or inflamed tissue.
Nanoparticles can be designed to release their cargo over a prolonged period allowing for controlled and sustained release of drugs, which can improve therapeutic outcomes and reduce side effects
What are peyer’s patches?
Clusters of lymphoid tissue found in the mucosa and submucosa of the small intestine, primarily in the ileum. They are masses of lymphatic tissue organized into follicles containing immune cells. They belong to the Gut-associated lymphoid tissue (GALT) and play a key role in immune function, particularly in the defense against pathogens that enter through the digestive tract.
Directly connected from GIT to lymphatic system, used for the uptake of fat.
Clinical functions and relevance:
Immune surveillance – monitoring the gut for pathogens by sampling the contents of the intestine. The Microfold (M) cells help by transcytosing antigens from the lumen to immune cells which initiate the immune response
Activation of adaptive immunity – when an antigen is detected, immune cells in the Peyer’s patches can trigger both local and systemic immune responses. This often involves the activation of B cells to produce antibodies, particularly IgA, which is important for mucosal immunity
Oral tolerance – Peyer’s patches also play a role in establishing oral tolerance, which prevents the immune system from overreacting to harmless substances like food proteins to commensal bacteria
Some pathogens like salmonella or shigella can specifically target Peyer’s patches to initiate infection
Conditions like Crohn’s disease or ulcerative colitis can affect Peyer’s patches via inflammation of the gut
Immunodeficiency can cause Peyer’s patches to be less effective at defending against intestinal infections
What are kupffer cells?
Specialised cells in the lumen of liver sinusoids (capillaries with discontinuous endothelium)
Have surface features such as microvilli, pseudopodia and lemellipodia
The primary function is to remove particles, apoptotic cells and debris that pass through the liver from the hepatic portal system. Large particles are taken up via phagocytosis and smaller particles are taken up by pinocytosis (a type of endocytosis in which a cell absorbs small particles from the extracellular fluid in vesicles)
In response to infection kupffer cells can produce inflammatory cytokines and proteases
What are enterocytes?
An almost continuous later of specialised epithelial cells lining the small intestine.
Have microvilli on surface, significantly increasing the surface area for absorption of nutrients. They absorb glucose via active transport using a sodium-glucose transporter
