Podcast
Questions and Answers
What is a common therapeutic action of drug delivery systems (DDS)?
What is a common therapeutic action of drug delivery systems (DDS)?
What primarily controls renal clearance for small molecules?
What primarily controls renal clearance for small molecules?
What mechanism is often referred to as target mediated drug disposition (TMDD)?
What mechanism is often referred to as target mediated drug disposition (TMDD)?
Which component is crucial for the prolonged circulation half-life of certain proteins such as monoclonal antibodies?
Which component is crucial for the prolonged circulation half-life of certain proteins such as monoclonal antibodies?
Signup and view all the answers
Where are drug delivery systems primarily eliminated from the body?
Where are drug delivery systems primarily eliminated from the body?
Signup and view all the answers
What enhances the efficiency of nanoparticle recognition by phagocytes?
What enhances the efficiency of nanoparticle recognition by phagocytes?
Signup and view all the answers
How does the size of protein therapeutics affect their tissue uptake?
How does the size of protein therapeutics affect their tissue uptake?
Signup and view all the answers
Which of the following factors limits the distribution of drug delivery systems (DDS) in the absence of specific pathologies?
Which of the following factors limits the distribution of drug delivery systems (DDS) in the absence of specific pathologies?
Signup and view all the answers
What mechanism can slow the clearance of nanoparticles from circulation?
What mechanism can slow the clearance of nanoparticles from circulation?
Signup and view all the answers
Which type of transporters can modulate the distribution of small-molecule drugs?
Which type of transporters can modulate the distribution of small-molecule drugs?
Signup and view all the answers
Study Notes
Drug Delivery Systems
- Drug delivery systems (DDS) such as liposomes, nanocarriers, and affinity drug conjugates are used to improve the delivery of drugs to specific sites of action.
- Some DDS enhance drug delivery and also offer therapeutic benefits.
Drug Elimination
- Elimination of drugs occurs via different mechanisms and at different rates for different molecules.
- For small molecules, the primary routes of elimination are renal clearance and metabolic clearance.
- Renal clearance involves glomerular filtration, active secretion into urine, and reabsorption from tubules.
- Metabolic clearance, primarily in the liver, relies on the recognition of the drug molecule by drug-metabolizing enzymes like cytochrome P450.
- Peptides and small-protein therapeutics with molecular masses below the glomerular filtration threshold (approx. 60 kDa) are eliminated through renal clearance.
- Proteins not eliminated through urine undergo catabolic breakdown in the body, often via the endo-lysosomal pathway.
- Target-mediated drug disposition (TMDD) enhances protein breakdown if the protein interacts with an internalizing receptor and undergoes receptor-mediated endocytosis.
- Proteins with an Fc region (e.g., monoclonal antibodies and Fc fusion proteins) are protected from degradation by binding to the neonatal Fc receptor, resulting in long circulating half-lives.
Drug Delivery System Elimination
- The primary route of elimination for drug delivery systems is through the reticuloendothelial system (RES), which includes organs like the liver, spleen, bone marrow, and lungs.
- The RES contains phagocytic cells (macrophages) that recognize nanoparticles as foreign bodies and remove them from circulation.
- Opsonization with serum proteins (e.g., immunoglobulins and complement proteins) enhances nanoparticle removal by phagocytes.
- The clearance of nanoparticles can be decreased by improving their "stealthiness" using techniques like polyethylene glycol (PEG) conjugation.
- Targeted DDS can be eliminated via specific interactions with receptors, similar to TMDD in protein therapeutics.
Drug Distribution
- Distribution of drugs between blood and tissues significantly impacts drug efficacy and toxicity.
- Small-molecule drug distribution varies, potentially confined to plasma or distributed throughout the body, and can be predicted using molecular descriptors and plasma protein binding.
- Transporters in specific tissues can also affect small-molecule drug distribution.
- Protein therapeutic distribution depends on their molecular weight, with smaller proteins diffusing and penetrating tissues more efficiently due to enhanced diffusion and convective uptake.
- Receptor-mediated transcytosis can increase tissue uptake of proteins with high affinity for receptors like the transferrin receptor.
- Most DDS are larger than the typical endothelial cell pores, limiting their distribution to the vascular space.
- Fenestrations in tissues like the liver and spleen allow for DDS uptake via bulk fluid flow.
- DDS with affinity for receptors that undergo transcytosis can also enhance tissue distribution.
Studying That Suits You
Use AI to generate personalized quizzes and flashcards to suit your learning preferences.
Description
Explore the mechanisms and systems involved in drug delivery and elimination. This quiz covers important topics such as liposomes, nanocarriers, renal clearance, and metabolic clearance, emphasizing their roles in enhancing drug effectiveness and safety.
