Non-particle and nanoparticle systems MCQs With Answer

Introduction: This quiz collection on non-particle and nanoparticle systems has been designed specifically for M.Pharm students studying Proteins and Protein Formulations. It focuses on the principles of nanoparticle design, protein encapsulation, stabilization strategies, characterization techniques, and formulation challenges unique to protein therapeutics. Questions probe understanding of preparation methods (e.g., nanoprecipitation, emulsification), surface modifications, protein–excipient interactions, aggregation and immunogenicity risks, analytical methods such as DLS, zeta potential and SEC, and practical issues like sterilization, lyophilization and scale-up. Work through these MCQs to reinforce core concepts and prepare for advanced coursework and professional practice in protein-based nanomedicines.

Q1. Which mechanism primarily governs protein release from degradable polymeric nanoparticles like PLGA?

• Purely diffusion-controlled release through an intact polymer matrix
• Enzymatic cleavage of protein inside particles only
• Combination of polymer matrix degradation and diffusion
• Immediate desorption from the particle surface without matrix involvement

Correct Answer: Combination of polymer matrix degradation and diffusion

Q2. Which characterization technique gives the hydrodynamic diameter of protein-loaded nanoparticles in dispersion?

• Transmission electron microscopy (TEM)
• Dynamic light scattering (DLS)
• Scanning electron microscopy (SEM)
• Atomic force microscopy (AFM)

Correct Answer: Dynamic light scattering (DLS)

Q3. What is the primary role of polyethylene glycol (PEG) grafting on protein-loaded nanoparticles?

• To increase nanoparticle density for better sedimentation
• To reduce protein loading capacity by steric hindrance
• To provide stealth properties and reduce opsonization
• To catalyze polymer degradation in vivo

Correct Answer: To provide stealth properties and reduce opsonization

Q4. Which excipient is commonly used as a cryoprotectant during lyophilization of protein nanoparticles to preserve activity?

• Sodium chloride
• Sucrose or trehalose
• Polyvinyl alcohol (PVA)
• Sodium lauryl sulfate (SLS)

Correct Answer: Sucrose or trehalose

Q5. In the emulsification–solvent evaporation method for protein-loaded polymeric nanoparticles, what is a major risk to protein stability?

• Oxidation due to high polymer molecular weight
• Interfacial denaturation at the oil–water interface
• Over-crosslinking by glutaraldehyde in the aqueous phase
• Excessive ionic strength in organic phase

Correct Answer: Interfacial denaturation at the oil–water interface

Q6. Which parameter measured by zeta potential analysis is most predictive of colloidal stability of protein nanoparticle suspensions?

• Particle shape anisotropy
• Surface charge magnitude
• Core crystallinity
• Hydrophobicity index of polymer

Correct Answer: Surface charge magnitude

Q7. What is the main advantage of using ionotropic gelation (e.g., chitosan–TPP) for protein nanoparticle formation?

• Requires high temperatures for crosslinking
• Uses organic solvents that improve protein solubility
• Mild aqueous conditions that better preserve protein structure
• Provides irreversible covalent crosslinks that never degrade

Correct Answer: Mild aqueous conditions that better preserve protein structure

Q8. Which phenomenon describes the adsorption of serum proteins onto nanoparticles, altering their biological identity?

• Protein encapsulation
• Surface grafting
• Protein corona formation
• Electrostatic shielding

Correct Answer: Protein corona formation

Q9. For long-term stability of protein nanoparticles, which storage-related factor is most likely to accelerate aggregation?

• Low ionic strength
• Optimal pH near protein isoelectric point
• Storage at ultra-low temperatures (−80 °C)
• Presence of stabilizing sugars

Correct Answer: Optimal pH near protein isoelectric point

Q10. Which surface modification is most appropriate to actively target nanoparticles to cells expressing folate receptors?

• Conjugation of mannose residues
• Conjugation of folic acid (folate)
• PEGylation with methoxy-PEG
• Adsorption of albumin

Correct Answer: Conjugation of folic acid (folate)

Q11. What is a common cause of initial burst release observed with protein-loaded nanoparticles?

• Perfect homogeneous encapsulation of protein within the core
• High protein crystallinity inside the matrix
• Protein localized near or adsorbed on particle surface
• Exclusively enzymatic degradation-controlled release

Correct Answer: Protein localized near or adsorbed on particle surface

Q12. Which analytical technique can best detect subtle changes in secondary structure of proteins after nanoparticle formulation?

• High-performance liquid chromatography (HPLC)
• Circular dichroism (CD) spectroscopy
• Dynamic light scattering (DLS)
• Thermogravimetric analysis (TGA)

Correct Answer: Circular dichroism (CD) spectroscopy

Q13. Which parameter defines encapsulation efficiency in protein-loaded nanoparticles?

• Mass of polymer divided by total formulation volume
• Percentage of initial protein incorporated into particles relative to total protein used
• Number of nanoparticles per mL of dispersion
• Molecular weight of the encapsulated protein

Correct Answer: Percentage of initial protein incorporated into particles relative to total protein used

Q14. Which sterilization method is least suitable for protein-loaded nanoparticles due to likely protein denaturation?

• Filtration through 0.22 µm membrane (if pore size allows)
• Gamma irradiation at high doses
• Sterile aseptic manufacturing without terminal sterilization
• Low-temperature ethylene oxide if validated

Correct Answer: Gamma irradiation at high doses

Q15. In nanoprecipitation for making polymeric nanoparticles, what is the driving force for particle formation?

• Evaporation of nonvolatile aqueous phase
• Phase separation upon mixing of solvent and nonsolvent causing polymer precipitation
• Enzymatic crosslinking of polymer chains
• Solidification by cooling crystalline polymer

Correct Answer: Phase separation upon mixing of solvent and nonsolvent causing polymer precipitation

Q16. Which approach most effectively reduces aggregation of therapeutic proteins during encapsulation?

• Exposing protein to strong interfaces without surfactants
• Using chaotropic salts to unfold proteins before encapsulation
• Inclusion of stabilizing excipients (e.g., sugars, amino acids, surfactants)
• High-energy sonication without temperature control

Correct Answer: Inclusion of stabilizing excipients (e.g., sugars, amino acids, surfactants)

Q17. Which nanoparticle type is formed by self-assembly of amphiphilic block copolymers and typically presents a hydrophobic core with hydrophilic corona?

• Solid lipid nanoparticle
• Polymeric micelle
• Inorganic gold nanoparticle
• Protein fibril aggregate

Correct Answer: Polymeric micelle

Q18. Which in vitro assay is commonly used to evaluate immunogenic potential or innate immune activation by nanoparticle formulations?

• Measurement of particle zeta potential only
• Cytokine release assay in immune cells (e.g., IL-6, TNF-α)
• Determination of melting point by DSC
• Measurement of bulk viscosity of dispersion

Correct Answer: Cytokine release assay in immune cells (e.g., IL-6, TNF-α)

Q19. Which factor most influences cellular uptake of nanoparticles via endocytosis?

• Zeta potential, size and surface ligand presentation
• Color of the nanoparticle suspension
• Manufacturing scale (lab vs. industrial)
• Bulk polymer crystallinity measured by XRD

Correct Answer: Zeta potential, size and surface ligand presentation

Q20. Which strategy can improve oral bioavailability of a protein delivered via nanoparticles?

• Using large particles (>5 µm) to avoid uptake
• Incorporating protease inhibitors and mucoadhesive polymers
• Avoiding any surface modification to promote rapid clearance
• Formulating at the protein’s isoelectric point to enhance aggregation

Correct Answer: Incorporating protease inhibitors and mucoadhesive polymers

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