Therapeutic peptides and delivery systems MCQs With Answer

Therapeutic peptides and delivery systems MCQs With Answer

Introduction: This set of multiple-choice questions is designed for M.Pharm students specializing in Advanced Pharmaceutical Biotechnology. The MCQs focus on therapeutic peptides—their design, stability challenges, chemical modifications, and various delivery systems used to enhance bioavailability and target specificity. Questions cover mechanisms of enzymatic degradation, strategies like PEGylation, lipid and polymeric carriers, cell-penetrating peptides, and novel formulations for non-invasive administration. Each question emphasizes conceptual understanding and practical considerations encountered during peptide drug development, formulation, and clinical translation. Use these items for revision, self-assessment, and exam preparation to deepen your mastery of peptide therapeutics and delivery approaches.

Q1. Which characteristic most accurately defines therapeutic peptides compared to small-molecule drugs?

• High molecular weight proteins exceeding 1000 amino acids
• Short chains of amino acids typically fewer than 50 residues
• Non-biologic low molecular weight organic compounds
• Polysaccharides derived from natural sources

Correct Answer: Short chains of amino acids typically fewer than 50 residues

Q2. What is the primary cause of rapid clearance of unmodified therapeutic peptides in vivo?

• Renal filtration and proteolytic degradation by peptidases
• Accumulation in adipose tissue
• Poor binding to plasma proteins causing aggregation
• Active efflux by P-glycoprotein in hepatocytes

Correct Answer: Renal filtration and proteolytic degradation by peptidases

Q3. Which chemical modification is commonly used to increase peptide half-life by reducing renal clearance and proteolysis?

• Hydroxylation of serine residues
• PEGylation (attachment of polyethylene glycol chains)
• Phosphorylation of the N-terminal residue
• Glycosylation with long mannose chains

Correct Answer: PEGylation (attachment of polyethylene glycol chains)

Q4. Stapled peptides are engineered primarily to improve which property?

• Oral absorption via intestinal transporters
• Helical stability and cell permeability
• Ability to chelate metal ions
• Hydrolytic susceptibility to carboxypeptidases

Correct Answer: Helical stability and cell permeability

Q5. Which delivery system provides protection from proteases and can enable sustained release of peptide drugs?

• Lipid-based nanoparticles (liposomes, solid lipid nanoparticles)
• Simple aqueous solutions for intravenous injection
• Uncoated glass vials stored at 37°C
• Free lyophilized peptide powder without excipients

Correct Answer: Lipid-based nanoparticles (liposomes, solid lipid nanoparticles)

Q6. Which method is most appropriate to evaluate peptide secondary structure and confirm effects of modifications like stapling?

• Nuclear magnetic resonance (NMR) spectroscopy
• Infrared spectrophotometry using Kubelka–Munk theory
• Circular dichroism (CD) spectroscopy
• Thermogravimetric analysis (TGA)

Correct Answer: Circular dichroism (CD) spectroscopy

Q7. Cell-penetrating peptides (CPPs) are primarily used for which purpose in peptide therapeutics?

• To increase enzymatic degradation
• To facilitate intracellular delivery of cargos such as peptides, proteins, or nucleic acids
• To selectively target renal podocytes
• To promote rapid renal clearance

Correct Answer: To facilitate intracellular delivery of cargos such as peptides, proteins, or nucleic acids

Q8. Which strategy reduces immunogenicity of peptide therapeutics most effectively?

• Increasing peptide aggregation to mask epitopes
• Use of D-amino acids or sequence deimmunization and PEGylation
• Adding multiple charged residues to increase recognition by immune cells
• Storing peptides at high temperatures to denature epitopes

Correct Answer: Use of D-amino acids or sequence deimmunization and PEGylation

Q9. Oral delivery of peptides is challenging mainly due to which combination of factors?

• High lipophilicity and excessive membrane permeation
• Enzymatic degradation in GI tract and poor epithelial permeability
• Rapid crossing of the blood-brain barrier causing toxicity
• Excessive pH stability and lack of dissolution

Correct Answer: Enzymatic degradation in GI tract and poor epithelial permeability

Q10. Which excipient is commonly incorporated in peptide formulations to inhibit proteases and protect peptides in the gastrointestinal tract?

• Sodium chloride
• Enzyme inhibitors such as aprotinin or camostat
• High concentrations of ethanol
• Calcium carbonate as an inert filler

Correct Answer: Enzyme inhibitors such as aprotinin or camostat

Q11. Conjugation of peptides to Fc fragments or albumin-binding domains primarily aims to:

• Increase renal filtration and decrease half-life
• Enhance systemic half-life via neonatal Fc receptor (FcRn)-mediated recycling
• Promote immediate hepatic metabolism
• Reduce interaction with target receptors

Correct Answer: Enhance systemic half-life via neonatal Fc receptor (FcRn)-mediated recycling

Q12. Which technique is most suitable for assessing peptide encapsulation efficiency in polymeric nanoparticles?

• Dynamic light scattering (DLS) alone
• Quantification of unencapsulated peptide by centrifugation/filtration followed by HPLC
• Visual inspection of nanoparticle suspension color
• pH titration of the nanoparticle dispersion

Correct Answer: Quantification of unencapsulated peptide by centrifugation/filtration followed by HPLC

Q13. Which factor most strongly influences peptide stability during lyophilization and storage?

• Type and concentration of lyoprotectants (e.g., sugars like trehalose)
• Color of the container used for storage
• Presence of light only, irrespective of temperature
• Using distilled water instead of buffered solutions during formulation

Correct Answer: Type and concentration of lyoprotectants (e.g., sugars like trehalose)

Q14. Which delivery route is attractive for peptide vaccines to induce mucosal immunity?

• Intravenous bolus injection
• Oral or intranasal administration
• Intramuscular injection into the deltoid only
• Topical dermal application without penetration enhancers

Correct Answer: Oral or intranasal administration

Q15. Which of the following describes “protease-resistant” peptide design?

• Replacing L-amino acids with D-amino acids or N-methylation at cleavage sites
• Increasing the number of free termini to enhance protease access
• Reducing hydrophobic residues to increase protease binding
• Introducing multiple glycosylation sites on the backbone only

Correct Answer: Replacing L-amino acids with D-amino acids or N-methylation at cleavage sites

Q16. Which property of liposomes can be modified to prolong circulation time of peptide-loaded liposomes?

• Inclusion of cholesterol and surface PEGylation
• Decrease vesicle size to less than 10 nm
• Use of only anionic lipids without stabilizers
• Omitting buffer salts to reduce osmolarity

Correct Answer: Inclusion of cholesterol and surface PEGylation

Q17. Which analytical method is essential to confirm peptide identity and sequence after chemical modification?

• Mass spectrometry (MS), such as LC-MS/MS
• Optical rotation only
• Colorimetric ninhydrin assay without separation
• Simple pH measurement of peptide solution

Correct Answer: Mass spectrometry (MS), such as LC-MS/MS

Q18. Active targeting of peptide therapeutics to tumors is commonly achieved by:

• Conjugating targeting ligands (peptides, antibodies) that bind tumor-specific receptors
• Reducing particle size to >10 micrometers to avoid extravasation
• Using non-specific cationic surfaces to increase blood clearance
• Avoiding any surface modification to minimize receptor binding

Correct Answer: Conjugating targeting ligands (peptides, antibodies) that bind tumor-specific receptors

Q19. Which regulatory consideration is particularly important for peptide drug-device combination products (e.g., injectable peptide pumps)?

• Evaluation of device sterility, compatibility with peptide formulation, and combination product labeling
• Only the peptide stability; device regulation is optional
• Exemption from biocompatibility testing if device is single-use
• Device color matching to brand requirements as primary concern

Correct Answer: Evaluation of device sterility, compatibility with peptide formulation, and combination product labeling

Q20. Which innovation helps facilitate oral absorption of peptides by transiently opening epithelial tight junctions?

• Permeation enhancers such as bile salts, zonula occludens modulators, or medium-chain fatty acids
• Adding acid to lower gastric pH permanently
• Injectable adjuvants co-administered intramuscularly
• Increasing peptide molecular weight to >50 kDa

Correct Answer: Permeation enhancers such as bile salts, zonula occludens modulators, or medium-chain fatty acids

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