Enzyme-activated drug delivery systems MCQs With Answer

Enzyme-Activated Drug Delivery Systems MCQs With Answer

Enzyme-activated drug delivery systems harness disease-associated enzymes to trigger site-specific drug release, thereby enhancing efficacy while reducing systemic toxicity. In M. Pharm curricula, this topic bridges medicinal chemistry, pharmaceutics, and pharmacokinetics—covering prodrugs, linker chemistry, polymer–drug conjugates, nanocarriers, and tumor microenvironment biology. These MCQs emphasize clinically relevant enzymes (e.g., MMPs, cathepsins, β-glucuronidase), design elements like self-immolative spacers and peptide linkers, and translational platforms such as ADEPT, GDEPT, and PDEPT. You will also test your grasp of enzyme kinetics, intracellular trafficking, colon-specific delivery using microbial enzymes, and appropriate analytical and control strategies. Use this set to strengthen conceptual understanding and prepare for advanced research or exams in Drug Delivery Systems (MPH 102T).

Q1. What is the principal rationale for using enzyme-activated drug delivery systems in oncology?

• Uniform pH across healthy and diseased tissues
• Overexpression or compartmentalization of specific enzymes at disease sites
• Higher systemic circulation time of free drug
• Complete absence of enzymes in healthy tissues

Correct Answer: Overexpression or compartmentalization of specific enzymes at disease sites

Q2. The peptide linker GFLG (Gly-Phe-Leu-Gly) commonly used in polymer–drug conjugates is predominantly cleaved by which enzyme?

• MMP-2/9
• Cathepsin B
• Thymidine phosphorylase
• β-Glucuronidase

Correct Answer: Cathepsin B

Q3. Colon-specific azo-bond prodrugs (e.g., sulfasalazine) are activated mainly by which microbial enzyme in the large intestine?

• Lactase
• Azoreductase
• Pepsin
• Trypsin

Correct Answer: Azoreductase

Q4. In targeted prodrug activation, ADEPT stands for:

• Antibody-Directed Enzyme Prodrug Therapy
• Adaptive Drug Enzyme Processing Technology
• Advanced Dual Enzyme Prodrug Targeting
• Antigen-Dependent Enhanced Prodrug Transport

Correct Answer: Antibody-Directed Enzyme Prodrug Therapy

Q5. What is the primary role of a self-immolative spacer (e.g., p-aminobenzyl alcohol) in enzyme-activated prodrugs?

• To permanently bind the drug to the carrier
• To promote rapid 1,6-elimination after enzymatic cleavage, releasing the native drug
• To increase drug crystallinity in the carrier
• To inhibit plasma protein binding

Correct Answer: To promote rapid 1,6-elimination after enzymatic cleavage, releasing the native drug

Q6. Under conditions where [S] ≪ Km for the activating enzyme, the apparent release rate from an enzyme-activated system most closely follows:

• Zero-order kinetics with respect to substrate
• First-order kinetics with respect to substrate
• Second-order kinetics with respect to enzyme
• Michaelis inhibition kinetics

Correct Answer: First-order kinetics with respect to substrate

Q7. A peptide sequence widely used as an MMP-2/9-cleavable linker in tumor-targeted nanoparticles is:

• GFLG
• PLGLAG
• RGD
• KDEL

Correct Answer: PLGLAG

Q8. Cathepsin B-triggered drug release in polymer–drug conjugates typically occurs within which cellular compartment?

• Cytosol (neutral pH)
• Lysosomes (acidic pH)
• Nucleus (basic pH)
• Mitochondrial matrix (alkaline pH)

Correct Answer: Lysosomes (acidic pH)

Q9. Which control best confirms that drug release from a prodrug is due to specific enzyme activity in vitro?

• Increasing incubation temperature by 10 °C
• Replacing buffer with deionized water
• Using heat-inactivated enzyme under identical conditions
• Reducing ionic strength of the medium

Correct Answer: Using heat-inactivated enzyme under identical conditions

Q10. β-Glucuronidase-activated prodrugs are generally designed by:

• Masking the drug with a glucuronic acid moiety to be cleaved at disease sites
• Attaching a disulfide that is cleaved by β-Glucuronidase
• Forming a carbonate readily hydrolyzed by plasma esterases
• Polymerizing the drug via anhydride linkages

Correct Answer: Masking the drug with a glucuronic acid moiety to be cleaved at disease sites

Q11. A major clinical limitation observed in ADEPT approaches is:

• Complete lack of catalytic turnover of the enzyme
• Immunogenicity of non-human enzymes and anti-enzyme antibody formation
• Absolute inability of prodrugs to penetrate tumors
• Universal activation of prodrugs in healthy tissues

Correct Answer: Immunogenicity of non-human enzymes and anti-enzyme antibody formation

Q12. PDEPT, a strategy related to enzyme-prodrug therapy, stands for:

• Prodrug-Directed Enzymatic Protein Targeting
• Polymer-Directed Enzyme Prodrug Therapy
• Pharmacodynamic Enzyme Delivery Platform Technology
• Peptide-Dependent Enzyme Processing Therapy

Correct Answer: Polymer-Directed Enzyme Prodrug Therapy

Q13. Colon-specific dextran–drug conjugates rely on which microbial enzyme for drug release?

• Dextranase
• Alkaline phosphatase
• Amylase
• Pepsin

Correct Answer: Dextranase

Q14. In MMP-cleavable “PEG-shedding” nanoparticles, enzymatic cleavage within tumors primarily serves to:

• Increase PEG density to prolong circulation
• Remove PEG and expose cell-interacting ligands to enhance uptake
• Convert the drug into a less active metabolite
• Block endocytosis by increasing particle size

Correct Answer: Remove PEG and expose cell-interacting ligands to enhance uptake

Q15. The kinetic parameter that best reflects catalytic efficiency and substrate specificity of an activating enzyme at low substrate levels is:

• Vmax
• Km
• kcat/Km
• IC50

Correct Answer: kcat/Km

Q16. Which linker is most susceptible to nonspecific cleavage by ubiquitous plasma esterases, thereby reducing selectivity of enzyme activation?

• Simple aliphatic ester linkage
• GFLG peptide linker
• PLGLAG peptide linker
• β-Glucuronide linkage

Correct Answer: Simple aliphatic ester linkage

Q17. Capecitabine, a clinically used prodrug of 5-FU, is ultimately activated at tumor sites predominantly by which enzyme?

• Thymidine phosphorylase
• Carboxylesterase
• β-Glucuronidase
• Glutathione S-transferase

Correct Answer: Thymidine phosphorylase

Q18. Cathepsin B exhibits optimal activity for prodrug cleavage at approximately which pH range?

• 7.4–8.0
• 4.5–6.0
• 9.0–10.0
• 6.8–7.2

Correct Answer: 4.5–6.0

Q19. In ADEPT protocols, which step is used to minimize systemic prodrug activation before administering the prodrug?

• Infusion of a clearing agent to remove circulating antibody–enzyme
• Co-administration of a broad-spectrum protease inhibitor
• Immediate prodrug injection without delay
• High-dose steroid premedication

Correct Answer: Infusion of a clearing agent to remove circulating antibody–enzyme

Q20. Which analytical method most directly confirms the identity of the active drug released after enzymatic cleavage of a prodrug/linker?

• Dynamic light scattering (DLS)
• Zymography
• LC–MS/MS of the released fraction
• UV–Vis absorbance at a single wavelength

Correct Answer: LC–MS/MS of the released fraction

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