Liposome-based formulations MCQs With Answer

Introduction: Liposome-based formulations MCQs With Answer is designed for M.Pharm students specializing in protein and peptide therapeutics. This set of questions focuses on fundamental and advanced concepts of liposomal carriers for proteins: composition, preparation techniques, encapsulation challenges for macromolecules, stability and sterilization issues, characterization methods, and formulation strategies such as PEGylation and pH-sensitive systems. Emphasis is placed on practical formulation considerations—preventing protein aggregation, improving entrapment efficiency, controlling release, and selecting appropriate excipients and processing methods. Use these MCQs to test understanding, prepare for exams, or review critical decision points encountered when designing protein-loaded liposomes in research and industry settings.

Q1. Which component is the primary structural building block of liposome bilayers used for protein encapsulation?

• Cholesterol only
• Phospholipids such as phosphatidylcholine
• Poloxamer surfactants
• Sorbitan esters

Correct Answer: Phospholipids such as phosphatidylcholine

Q2. Which liposome type is characterized by a single phospholipid bilayer and a diameter typically less than 100 nm?

• Multilamellar vesicle (MLV)
• Giant unilamellar vesicle (GUV)
• Small unilamellar vesicle (SUV)
• Multivesicular vesicle (MVV)

Correct Answer: Small unilamellar vesicle (SUV)

Q3. Which preparation method is especially useful for achieving high aqueous core volume favorable for encapsulating proteins?

• Sonication of dry lipids
• Thin-film hydration without further processing
• Reverse-phase evaporation
• Direct ethanol injection

Correct Answer: Reverse-phase evaporation

Q4. Which technique is commonly employed to improve entrapment efficiency of large proteins into liposomes?

• Simple passive hydration at room temperature
• Dehydration–rehydration vesicle (DRV) method
• Direct adsorption of protein onto preformed SUVs only
• Sonication in the presence of strong detergents

Correct Answer: Dehydration–rehydration vesicle (DRV) method

Q5. What is the principal effect of adding cholesterol to liposomal bilayers for protein formulations?

• It increases bilayer permeability and protein leakage
• It causes liposomes to immediately aggregate
• It increases membrane rigidity and reduces permeability
• It converts liposomes into micelles

Correct Answer: It increases membrane rigidity and reduces permeability

Q6. PEGylation of liposomes is primarily used to:

• Increase bilayer fluidity to enhance immediate protein release
• Sterically stabilize the vesicle and prolong circulation time
• Promote rapid uptake by reticuloendothelial system macrophages
• Destabilize proteins to favor adsorption on the bilayer

Correct Answer: Sterically stabilize the vesicle and prolong circulation time

Q7. How does a high magnitude zeta potential influence colloidal stability of protein-loaded liposomes?

• It promotes rapid fusion and aggregation
• It increases colloidal stability by electrostatic repulsion
• It has no effect on stability, only size matters
• It always causes immediate precipitation

Correct Answer: It increases colloidal stability by electrostatic repulsion

Q8. For sterilizing protein-loaded liposome suspensions without damaging the protein, the preferred industry approach is:

• Autoclaving the final liposome suspension
• Gamma irradiation of the filled vials
• Aseptic manufacturing with sterile filtration of components and aseptic assembly
• Adding high concentration of ethanol and then filtering

Correct Answer: Aseptic manufacturing with sterile filtration of components and aseptic assembly

Q9. Which cryoprotectant is most commonly recommended to protect both lipids and encapsulated proteins during lyophilization?

• Glycerol at 40% v/v
• Trehalose
• Sodium chloride
• Polysorbate 80 only

Correct Answer: Trehalose

Q10. Increasing the ionic strength of the medium during liposome–protein interaction studies typically results in:

• Enhanced electrostatic adsorption of proteins to the bilayer
• Screening of electrostatic interactions and decreased protein adsorption
• Complete chemical denaturation of the protein
• Formation of covalent bonds between protein and lipids

Correct Answer: Screening of electrostatic interactions and decreased protein adsorption

Q11. pH-sensitive liposomes designed to trigger release in endosomes commonly contain which combination to enable fusogenic behavior at acidic pH?

• DSPC and high cholesterol only
• DOPE combined with CHEMS (cholesteryl hemisuccinate)
• PEGylated lipids exclusively
• Sorbitan monooleate and Tween 80

Correct Answer: DOPE combined with CHEMS (cholesteryl hemisuccinate)

Q12. Subjecting multilamellar liposomes to controlled freeze–thaw cycles commonly leads to:

• Decreased encapsulation due to permanent rupture of vesicles
• Enhanced fusion of bilayers and increased aqueous entrapment
• Conversion of phospholipids to triglycerides
• Complete removal of cholesterol from the bilayer

Correct Answer: Enhanced fusion of bilayers and increased aqueous entrapment

Q13. Which analytical technique provides the hydrodynamic diameter distribution of hydrated liposome populations and is commonly used during formulation development?

• Transmission electron microscopy (TEM) of dried samples only
• Dynamic light scattering (DLS)
• Nuclear magnetic resonance spectroscopy (NMR)
• Ultraviolet-visible spectrophotometry

Correct Answer: Dynamic light scattering (DLS)

Q14. Increasing the proportion of unsaturated phospholipids in a liposome formulation typically results in which effect on encapsulated proteins?

• Decreased membrane fluidity and slower release
• Increased bilayer fluidity and higher propensity for leakage
• Complete inactivation of proteins by oxidation-resistant bilayers
• Formation of covalent lipid–protein conjugates

Correct Answer: Increased bilayer fluidity and higher propensity for leakage

Q15. Which loading strategy uses an established transmembrane ion or pH gradient to actively load ionizable small molecules but is generally not suitable for large proteins?

• Passive encapsulation during thin-film hydration
• Remote (active) loading using an ammonium sulfate or pH gradient
• Dehydration–rehydration of preformed liposomes
• Direct covalent attachment to lipid headgroups

Correct Answer: Remote (active) loading using an ammonium sulfate or pH gradient

Q16. Which class of liposomes is most associated with increased complement activation and infusion-related reactions in vivo?

• Neutral PEGylated liposomes
• Anionic DOPS-rich liposomes
• Cationic liposomes
• Cholesterol-free saturated liposomes

Correct Answer: Cationic liposomes

Q17. To minimize aggregation of a model protein during encapsulation, the formulation buffer pH should ideally be:

• At the protein’s isoelectric point
• Highly acidic (pH 1–2) regardless of protein
• Away from the protein’s isoelectric point (at least 1–2 pH units)
• Extremely alkaline (pH >13)

Correct Answer: Away from the protein’s isoelectric point (at least 1–2 pH units)

Q18. Incorporating PEG-lipids into liposome formulations most directly reduces which of the following in vivo?

• Encapsulation efficiency of hydrophilic proteins
• Opsonization and clearance by the reticuloendothelial system
• Bilayer mechanical strength causing immediate rupture
• Protein denaturation inside the aqueous core

Correct Answer: Opsonization and clearance by the reticuloendothelial system

Q19. Hydrophilic proteins encapsulated in liposomes are primarily located:

• Intercalated within the hydrophobic core of the bilayer
• Adsorbed exclusively on the outer bilayer surface only
• Within the aqueous core of the liposome
• Covalently bound to cholesterol molecules

Correct Answer: Within the aqueous core of the liposome

Q20. Which formulation modification is most likely to slow the release of an encapsulated protein from liposomes?

• Removing cholesterol and using highly unsaturated lipids
• Increasing cholesterol content to rigidify the membrane
• Reducing lipid-to-protein ratio drastically
• Converting vesicles to micelles by adding detergents

Correct Answer: Increasing cholesterol content to rigidify the membrane

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