Liposomes: preparation and evaluation MCQs With Answer
For M. Pharm students specializing in Molecular Pharmaceutics/NTDS, mastering liposome technology is essential for designing advanced nanocarriers. This MCQ set focuses on practical and mechanistic aspects of liposome preparation and evaluation—covering lipid selection, methods like thin-film hydration, ethanol injection, reverse-phase evaporation and microfluidics, as well as critical quality attributes such as particle size, PDI, zeta potential, lamellarity, encapsulation efficiency, and release kinetics. You’ll also find questions on PEGylation, remote loading, sterilization, lyophilization, analytical techniques (DLS, 31P-NMR, DSC, HPLC, cryo-TEM), and stability considerations. Each question is crafted to test deep understanding and decision-making skills relevant to formulation development and regulatory expectations for liposomal drug products.
Q1. Which phospholipid is most appropriate when a high bilayer phase-transition temperature (Tm) is required for stable liposomes?
- DSPC (1,2-distearoyl-sn-glycero-3-phosphocholine)
- DOPC (1,2-dioleoyl-sn-glycero-3-phosphocholine)
- Egg PC (L-α-phosphatidylcholine, unsaturated)
- DOPE (1,2-dioleoyl-sn-glycero-3-phosphoethanolamine)
Correct Answer: DSPC (1,2-distearoyl-sn-glycero-3-phosphocholine)
Q2. What is the primary role of cholesterol in conventional phospholipid bilayers?
- Increase bilayer permeability and leakage
- Reduce bilayer permeability and leakage by ordering acyl chains
- Impart a strong negative surface charge
- Promote micelle formation over bilayer formation
Correct Answer: Reduce bilayer permeability and leakage by ordering acyl chains
Q3. In the thin-film hydration method, which step is critical to form multilamellar vesicles (MLVs)?
- Hydrating the lipid film below the Tm of the highest-melting lipid
- Evaporating organic solvent to form a thin, dry lipid film under reduced pressure, then hydrating above Tm
- Injecting lipids in ethanol directly into cold aqueous buffer
- Freeze–thawing the dispersion before forming the lipid film
Correct Answer: Evaporating organic solvent to form a thin, dry lipid film under reduced pressure, then hydrating above Tm
Q4. Active remote loading of doxorubicin into liposomes most commonly relies on which transmembrane gradient?
- Ammonium sulfate gradient
- Sodium chloride gradient
- Glucose gradient
- Urea gradient
Correct Answer: Ammonium sulfate gradient
Q5. PEGylation of liposomes most consistently results in which effect?
- Accelerated opsonization and rapid RES clearance
- Reduced opsonization and prolonged systemic circulation
- Increased hemolysis due to surface hydration
- Higher bilayer Tm due to PEG-lipid incorporation
Correct Answer: Reduced opsonization and prolonged systemic circulation
Q6. In dynamic light scattering (DLS), which reported parameter reflects the breadth of the size distribution?
- Zeta potential
- Polydispersity index (PDI)
- Encapsulation efficiency
- Phase-transition temperature (Tm)
Correct Answer: Polydispersity index (PDI)
Q7. Which analytical technique can quantify liposome lamellarity non-destructively in bulk dispersions?
- 31P-NMR spectroscopy
- UV–Visible spectroscopy
- Differential scanning calorimetry (DSC)
- High-performance liquid chromatography (HPLC)
Correct Answer: 31P-NMR spectroscopy
Q8. A rigorous approach to determine encapsulation efficiency (EE%) of a hydrophilic drug in liposomes is:
- Measuring intensity-weighted size distribution by DLS
- Separating free drug (e.g., by dialysis or centrifugation), disrupting liposomes with surfactant/solvent, then quantifying by HPLC
- Monitoring turbidity at 600 nm
- Determining moisture content by Karl Fischer titration
Correct Answer: Separating free drug (e.g., by dialysis or centrifugation), disrupting liposomes with surfactant/solvent, then quantifying by HPLC
Q9. Which zeta potential magnitude is generally indicative of good electrostatic stabilization in aqueous liposomal dispersions?
- Approximately 0 mV
- ±5 mV
- ±15 mV
- ≥ ±30 mV
Correct Answer: ≥ ±30 mV
Q10. What is the most suitable sterilization method for nanosized liposomes (~100–200 nm) containing heat-labile drugs?
- Autoclaving at 121°C
- Dry heat sterilization
- Sterile filtration through a 0.22 μm membrane
- Gamma irradiation
Correct Answer: Sterile filtration through a 0.22 μm membrane
Q11. Which excipient is widely used as a cryo/lyoprotectant to prevent fusion and leakage during liposome lyophilization?
- Mannitol
- Trehalose
- Sodium chloride
- EDTA
Correct Answer: Trehalose
Q12. The most commonly employed in vitro method to assess drug release from liposomes in suspension is:
- Dialysis bag diffusion under sink conditions
- USP rotating basket apparatus
- USP paddle apparatus (Type II) without a membrane
- Gas sorption analysis
Correct Answer: Dialysis bag diffusion under sink conditions
Q13. Which phospholipid is most prone to oxidative degradation, requiring antioxidants and low-oxygen handling?
- DSPC (fully saturated)
- DOPC (polyunsaturated)
- HSPC (hydrogenated soy PC)
- DPPC (fully saturated)
Correct Answer: DOPC (polyunsaturated)
Q14. Which cationic lipid is commonly used to formulate gene-delivery liposomes due to its positive charge?
- HSPC
- DOTAP
- Cholesterol
- DSPE-PEG2000
Correct Answer: DOTAP
Q15. In microfluidic ethanol injection, increasing the aqueous-to-organic flow rate ratio (FRR) typically:
- Increases particle size due to slower mixing
- Decreases particle size by promoting rapid nucleation and self-assembly
- Has no effect on particle size
- Only increases encapsulation efficiency without affecting size
Correct Answer: Decreases particle size by promoting rapid nucleation and self-assembly
Q16. During hydration of a lipid film, the hydration temperature should be:
- Below the Tm of the highest-melting lipid component
- At least 5–10°C above the Tm of the highest-melting lipid
- At ambient temperature regardless of lipid composition
- On ice to minimize leakage
Correct Answer: At least 5–10°C above the Tm of the highest-melting lipid
Q17. Active remote loading using a transmembrane pH or ammonium sulfate gradient is most efficient for:
- Highly lipophilic neutral drugs (e.g., paclitaxel)
- Weakly basic amphipathic drugs (e.g., doxorubicin)
- Highly hydrophilic neutral sugars (e.g., mannitol)
- Large peptides/proteins without ionizable groups
Correct Answer: Weakly basic amphipathic drugs (e.g., doxorubicin)
Q18. Which combination best favors EPR-mediated tumor accumulation of liposomes after intravenous administration?
- Size ~300 nm, cationic surface, non-PEGylated
- Size ~100 nm, PEGylated surface, near-neutral to mildly negative zeta potential
- Size ~40 nm, highly positive zeta potential, non-PEGylated
- Size ~200 nm, strongly negative zeta potential, non-PEGylated
Correct Answer: Size ~100 nm, PEGylated surface, near-neutral to mildly negative zeta potential
Q19. Which of the following is NOT a typical Critical Quality Attribute (CQA) for a liposomal drug product?
- Mean particle size and PDI
- Encapsulation efficiency
- Zeta potential
- Tablet hardness
Correct Answer: Tablet hardness
Q20. Differential Scanning Calorimetry (DSC) is primarily used in liposome evaluation to determine:
- Zeta potential
- Bilayer phase-transition temperature and lipid polymorphism
- Lamellarity
- Drug content directly in dispersion without separation
Correct Answer: Bilayer phase-transition temperature and lipid polymorphism

I am a Registered Pharmacist under the Pharmacy Act, 1948, and the founder of PharmacyFreak.com. I hold a Bachelor of Pharmacy degree from Rungta College of Pharmaceutical Science and Research. With a strong academic foundation and practical knowledge, I am committed to providing accurate, easy-to-understand content to support pharmacy students and professionals. My aim is to make complex pharmaceutical concepts accessible and useful for real-world application.
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