Lecture 16 Polymer-drug Conjugates Flashcards
Describe the concept of a prodrug and why it is necessary in medication.
A prodrug is a medication that is inactive when administered but becomes active through chemical changes in the body. Prodrugs are necessary for improved pharmacokinetics, enhanced targeting, reduced toxicity, improved stability, masking unpleasant properties, patent protection, and overcoming biological barriers.
What are the types of bond cleavage allowing for prodrug-drug conversion?
The types of bond cleavage allowing for prodrug-drug conversion include Ester Bonds, Amide Bonds, Hydrazone Bonds, and Disulfide Bonds. Enzymes in the body break down these bonds, converting the inactive prodrug to an active drug.
How are polymer-drug conjugates formed and what is their purpose?
Polymer-drug conjugates are constructs formed by therapeutic drugs with polymeric carriers. These carriers, typically polymers, serve as delivery vehicles for drugs, enhancing solubility, stability, bioavailability, and targeted delivery.
Describe the components of polymer-drug conjugates.
Polymer-drug conjugates contain a polymer backbone, a cleavable linker, and the drug itself. These components work together to improve drug delivery, solubility, stability, and bioavailability.
Explain the significance of Adagen, the first polymer-drug conjugate on the market in 1990.
Adagen, the first polymer-drug conjugate on the market in 1990, marked a milestone in drug delivery technology. It demonstrated the potential of polymer-drug conjugates in enhancing drug solubility, stability, and targeted delivery, paving the way for future innovations.
Describe the characteristics and benefits of polymer-protein conjugates, focusing on the use of PEG as the polymer of choice and its impact protein immunogenicity, solubility, and plasma half-life.
Polymer-protein conjugates, with PEG as a common polymer, enhance solubility, reduce immunogenicity, and extend plasma half-life. PEG, a biocompatible polymer, improves aqueous solubility and stability. Examples like Adagen show efficacy in treating conditions like severe combined immunodeficiency.
How do dendrimers function as polymer-small-molecule drug conjugates, and what makes them suitable for drug delivery? Provide an example of a product that utilizes dendrimers for this purpose.
Dendrimers are highly branched polymeric macromolecules with controlled properties, making them ideal drug carriers. VivaGel, a microbicidal gel, uses dendrimers to prevent sexually transmitted infections like HIV and herpes simplex virus by acting as nanocarriers with high surface functionality.
Define polymer nanoparticles and explain their role as drug delivery vehicles, highlighting their structure, targeting capabilities, and the importance of surface functionalization.
Polymeric nanoparticles, colloidal carriers on the nanoscale, are used for drug delivery. They typically have a shell-core structure, target specific cells and tissues, and require surface functionalization for prolonged circulation and tissue internalization. These nanoparticles are crucial in enhancing drug delivery efficiency.
Describe the benefits and characteristics of polymer-protein conjugates compared to polymer-small-molecule drug conjugates, focusing on their impact on solubility, stability, and plasma half-life.
Polymer-protein conjugates, like those using PEG, offer improved solubility, stability, and extended plasma half-life compared to polymer-small-molecule drug conjugates. They also provide active intracellular delivery, altered biodistribution, and potential for targeted delivery through incorporation of targeting moieties.
How are polymer-protein conjugates different from polymer nanoparticles in terms of structure, function, and application in drug delivery?
Polymer-protein conjugates involve attaching proteins to polymers like PEG to enhance solubility, stability, and plasma half-life, while polymer nanoparticles are colloidal carriers with nanoscale dimensions used for drug delivery. The former focuses on protein modification, while the latter emphasizes targeted drug delivery and tissue internalization.
Describe the concept of stimuli-sensitive polymer-drug conjugates and their role in drug delivery systems. What are the common types of stimuli these polymers respond to?
Stimuli-sensitive polymer-drug conjugates are smart drug delivery systems that react to specific stimuli in the body to trigger drug release. They respond to pH, temperature, enzymes, light, or magnetic fields. Common types include pH-sensitive, temperature-sensitive, enzyme-sensitive, light-sensitive, and magnetic/ultrasound-sensitive polymers.
What are enzyme-sensitive linkers in the context of stimuli-sensitive polymer-drug conjugates?
Enzyme-sensitive linkers are components of stimuli-sensitive polymer-drug conjugates that respond to enzymatic activity in the body, leading to drug release. These linkers are designed to undergo specific changes in the presence of certain enzymes, facilitating targeted drug delivery.
How does surface-charge switching contribute to the functionality of stimuli-sensitive polymer-drug conjugates?
Surface-charge switching is a mechanism in stimuli-sensitive polymer-drug conjugates where changes in charge on the polymer surface trigger drug release. This feature allows for controlled drug delivery based on alterations in the polymer’s surface charge in response to stimuli.
