Controlled delivery of proteins MCQs With Answer

Controlled delivery of proteins MCQs With Answer

Introduction: This quiz set on controlled delivery of proteins is designed for M.Pharm students specializing in Advanced Pharmaceutical Biotechnology. It focuses on formulation strategies, physicochemical and biological challenges of protein therapeutics, delivery systems (nanoparticles, liposomes, hydrogels, microspheres, implants), stabilization techniques, release mechanisms, analytical assessment and regulatory considerations. Questions stimulate deeper understanding of how to design stable, effective protein delivery systems, predict release kinetics, mitigate immunogenicity and scale-up manufacturing. Use these MCQs to test conceptual knowledge, apply practical formulation choices and reinforce principles critical for developing next-generation protein therapeutics with improved efficacy and patient compliance.

Q1. What is the primary reason proteins are more challenging to deliver in controlled-release formulations compared to small-molecule drugs?

• Higher chemical stability in solution
• Lower molecular weight leading to rapid diffusion
• Susceptibility to denaturation, aggregation and proteolytic degradation
• Greater lipophilicity causing tissue accumulation

Correct Answer: Susceptibility to denaturation, aggregation and proteolytic degradation

Q2. Which method is commonly used to encapsulate proteins into PLGA microspheres while minimizing protein denaturation?

• Single emulsion (oil-in-water) with high shear
• Spray-drying from aqueous solution
• Double emulsion (water-in-oil-in-water) with optimized stabilizers
• Direct melt extrusion at 150°C

Correct Answer: Double emulsion (water-in-oil-in-water) with optimized stabilizers

Q3. Which excipient is frequently added to protein formulations to protect the protein during freeze-drying (lyophilization)?

• Sodium lauryl sulfate
• Sucrose or trehalose as cryo/lyoprotectant
• Polyethyleneimine
• Calcium carbonate

Correct Answer: Sucrose or trehalose as cryo/lyoprotectant

Q4. PEGylation of proteins primarily aims to achieve which of the following outcomes?

• Increase immunogenicity
• Decrease circulation half-life
• Improve solubility, reduce clearance and decrease immunogenicity
• Increase enzymatic degradation rate

Correct Answer: Improve solubility, reduce clearance and decrease immunogenicity

Q5. Which release mechanism is most associated with biodegradable polymer matrices like PLGA?

• Pore-forming osmotic pump release only
• Diffusion-controlled release without polymer degradation
• Combination of diffusion and polymer degradation (erosion-controlled)
• Immediate burst followed by no further release

Correct Answer: Combination of diffusion and polymer degradation (erosion-controlled)

Q6. What is the major cause of the initial burst release observed in many protein-loaded microparticles?

• Slow polymer degradation kinetics
• Protein strongly bound to polymer matrix
• Surface-associated protein and poorly encapsulated fraction
• High crystallinity of encapsulated protein

Correct Answer: Surface-associated protein and poorly encapsulated fraction

Q7. Affinity-based delivery systems for proteins often use which strategy to modulate release?

• Entrapment in hydrophobic oils only
• Non-specific ionic complexation with any charged molecule
• Specific reversible binding between protein and immobilized ligand or receptor-mimetic
• Conjugation through irreversible covalent bonds to polymer backbone

Correct Answer: Specific reversible binding between protein and immobilized ligand or receptor-mimetic

Q8. Which route of administration is commonly chosen for long-acting protein depot formulations to enhance patient compliance?

• Topical ocular application
• Subcutaneous or intramuscular injection
• Inhalation via dry powder
• Oral immediate-release tablet

Correct Answer: Subcutaneous or intramuscular injection

Q9. Which analytical method is most appropriate for detecting protein aggregation in a controlled-release formulation?

• Gas chromatography
• Size-exclusion chromatography (SEC) with light scattering
• Infrared spectroscopy for small organics
• pH titration

Correct Answer: Size-exclusion chromatography (SEC) with light scattering

Q10. In designing a controlled-release hydrogel for protein delivery, which property of the hydrogel most directly controls protein diffusion rate?

• Hydrogel color
• Mesh (pore) size and crosslinking density
• Molecular weight of the protein only
• Surface hydrophobicity of the container

Correct Answer: Mesh (pore) size and crosslinking density

Q11. What is a common strategy to reduce immunogenicity of therapeutic proteins delivered by controlled systems?

• Repeated high-dose bolus injections
• Use of strong pro-inflammatory adjuvants
• Site-specific PEGylation or glycoengineering to mask immunogenic epitopes
• Adding endotoxin contamination intentionally

Correct Answer: Site-specific PEGylation or glycoengineering to mask immunogenic epitopes

Q12. Which solvent used in protein encapsulation by solvent evaporation is most damaging and typically avoided or removed thoroughly?

• Water
• Hexane
• Organic solvents like dichloromethane (DCM) or ethyl acetate if residual remains
• Sucrose solution

Correct Answer: Organic solvents like dichloromethane (DCM) or ethyl acetate if residual remains

Q13. Which property of a microsphere formulation is quantified by ‘encapsulation efficiency’?

• Percentage of polymer crystallinity
• Fraction of initial protein successfully entrapped within particles
• pH of the microsphere suspension
• Viscosity of the organic phase

Correct Answer: Fraction of initial protein successfully entrapped within particles

Q14. For achieving near zero-order release of a protein, which design approach is commonly used?

• Highly porous matrix with uncontrolled burst
• Osmotic pump or membrane-controlled reservoir system
• Immediate-release tablet
• Using only unmodified soluble protein in solution

Correct Answer: Osmotic pump or membrane-controlled reservoir system

Q15. Which factor most influences protein stability during spray drying encapsulation?

• Atomization temperature, inlet/outlet temperatures and use of stabilizing excipients
• Molecular imprints in polymer
• Color of the drying chamber
• Exposure to ultraviolet light only

Correct Answer: Atomization temperature, inlet/outlet temperatures and use of stabilizing excipients

Q16. What is the role of surfactants like polysorbate 20/80 in protein-containing controlled-release formulations?

• Promote protein adsorption to interfaces and aggregation
• Act as cryoprotectants during freeze-drying
• Reduce interfacial-induced denaturation and prevent aggregation
• Increase proteolytic degradation

Correct Answer: Reduce interfacial-induced denaturation and prevent aggregation

Q17. Which release kinetic model is often used as a simple descriptor for matrix-controlled diffusion of macromolecules?

• Michaelis-Menten kinetics
• Higuchi model describing square-root-of-time release
• Arrhenius equation
• Langmuir isotherm

Correct Answer: Higuchi model describing square-root-of-time release

Q18. Which manufacturing challenge is particularly critical when scaling up protein-loaded nanoparticle production?

• Maintaining aseptic conditions, reproducible particle size and protein stability
• Changing the therapeutic protein sequence
• Removing all water from the formulation
• Converting protein into a small molecule

Correct Answer: Maintaining aseptic conditions, reproducible particle size and protein stability

Q19. Which characteristic of the protein itself most strongly affects its release from a charged polyelectrolyte matrix?

• Isoelectric point (pI) and net charge at formulation pH
• Number of disulfide bonds only
• Color of the protein solution
• Presence of heavy metals

Correct Answer: Isoelectric point (pI) and net charge at formulation pH

Q20. Why is establishing an in vitro–in vivo correlation (IVIVC) important for protein-controlled release products?

• It is unnecessary for regulatory approval
• To predict clinical performance from in vitro release and support dosage form optimization and regulatory acceptance
• Because proteins do not degrade in vivo
• To ensure the product tastes acceptable

Correct Answer: To predict clinical performance from in vitro release and support dosage form optimization and regulatory acceptance

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