Brain-specific drug delivery MCQs With Answer

Brain-specific drug delivery MCQs With Answer is designed to help M. Pharm students master key concepts in overcoming the blood–brain barrier (BBB) and optimizing central nervous system (CNS) pharmacotherapy. This set covers mechanistic insights into BBB structure and transport pathways, advanced strategies like receptor- and adsorptive-mediated transcytosis, intranasal and focused ultrasound-assisted delivery, nanoparticle and exosome platforms, and pharmacokinetic readouts such as Kp,uu,brain. You will also find questions on in vitro BBB models, efflux transporters, convection-enhanced delivery, and the glymphatic system, ensuring both breadth and depth. Each MCQ has been curated to reflect current translational approaches and quantitative assessment tools, empowering you to critically evaluate and design brain-targeted delivery systems in molecular pharmaceutics.

Q1. Which structural feature is primarily responsible for the restrictive paracellular barrier of the blood–brain barrier (BBB)?

• Continuous tight junctions with claudins and occludin
• Fenestrated endothelium with high transcytosis
• Discontinuous sinusoidal capillaries
• Absence of basement membrane

Correct Answer: Continuous tight junctions with claudins and occludin

Q2. Transferrin- or insulin-receptor–targeted nanocarriers cross the BBB predominantly via which pathway?

• Paracellular diffusion
• Carrier-mediated transport for glucose
• Receptor-mediated transcytosis
• Passive transmembrane diffusion

Correct Answer: Receptor-mediated transcytosis

Q3. Which physicochemical profile most favors passive BBB permeation for small molecules?

• MW < 400 Da, PSA < 70 Ų, logP 2–4, hydrogen bond donors ≤ 2
• MW > 700 Da, PSA > 120 Ų, logP < 1
• Highly ionized at physiological pH with PSA > 100 Ų
• MW 500–800 Da with strong P-gp substrate motifs

Correct Answer: MW < 400 Da, PSA < 70 Ų, logP 2–4, hydrogen bond donors ≤ 2

Q4. Which efflux transporter most commonly limits brain exposure of many lipophilic drugs at the BBB?

• OATP1A2
• P-glycoprotein (ABCB1) at the luminal membrane
• PEPT2
• NTCP

Correct Answer: P-glycoprotein (ABCB1) at the luminal membrane

Q5. Among in vitro BBB models, which generally achieves the highest transendothelial electrical resistance (TEER) and closer physiological tightness?

• hCMEC/D3 monoculture on Transwell
• MDCK-MDR1 overexpressing cells
• Primary bovine brain endothelial cells alone
• iPSC-derived brain microvascular endothelial cells co-cultured with astrocytes/pericytes

Correct Answer: iPSC-derived brain microvascular endothelial cells co-cultured with astrocytes/pericytes

Q6. Which metric best reflects net unbound drug penetration into brain at steady state?

• Total brain-to-plasma ratio (Kp,brain)
• LogBB (log Cbrain/log Cblood)
• CSF/plasma total concentration ratio
• Unbound brain-to-plasma ratio (Kp,uu,brain)

Correct Answer: Unbound brain-to-plasma ratio (Kp,uu,brain)

Q7. Intranasal nose-to-brain delivery primarily utilizes which anatomical routes?

• Auditory canal and Eustachian tube pathways
• Olfactory and trigeminal nerve pathways
• Direct vascular uptake via nasal veins
• Lymphatic drainage to cervical nodes only

Correct Answer: Olfactory and trigeminal nerve pathways

Q8. Angiopep-2 facilitates brain delivery by targeting which receptor on brain endothelial cells?

• Folate receptor alpha
• Transferrin receptor
• LRP1 (low-density lipoprotein receptor–related protein 1)
• Nicotinic acetylcholine receptor

Correct Answer: LRP1 (low-density lipoprotein receptor–related protein 1)

Q9. Focused ultrasound (FUS) with microbubbles enhances BBB permeability mainly through:

• Thermal ablation of endothelial cells
• Acoustic cavitation of microbubbles causing reversible tight junction modulation and enhanced transcytosis
• Permanent pore formation in the basement membrane
• Activation of leukocyte-mediated diapedesis

Correct Answer: Acoustic cavitation of microbubbles causing reversible tight junction modulation and enhanced transcytosis

Q10. Which statement best describes LAT1 (SLC7A5)-mediated brain delivery strategies?

• L-DOPA crosses the BBB via LAT1, which transports large neutral amino acids
• LAT1 transports cationic peptides via adsorptive-mediated transcytosis
• LAT1 is an efflux pump that expels amino acids from brain to blood
• LAT1 is only expressed in neurons, not endothelial cells

Correct Answer: L-DOPA crosses the BBB via LAT1, which transports large neutral amino acids

Q11. Which statement about cerebrospinal fluid (CSF) as a surrogate for brain interstitial concentrations is most accurate?

• CSF concentrations always mirror unbound brain interstitial levels
• CSF is a reliable surrogate only for highly protein-bound drugs
• CSF concentrations often do not reflect unbound brain interstitial concentrations
• CSF is superior to brain microdialysis for local tissue exposure assessment

Correct Answer: CSF concentrations often do not reflect unbound brain interstitial concentrations

Q12. Convection-enhanced delivery (CED) improves intraparenchymal drug distribution because it relies on:

• Passive diffusion along a concentration gradient
• Receptor-mediated endocytosis into endothelial cells
• Pressure-driven bulk flow through the extracellular space
• Retrograde axonal transport from terminals to soma

Correct Answer: Pressure-driven bulk flow through the extracellular space

Q13. A key advantage of exosome-based carriers for brain drug delivery is:

• Guaranteed absence of immune recognition
• Intrinsic biogenesis, biocompatibility, and the ability to cross the BBB with low immunogenicity
• Unlimited drug loading regardless of cargo properties
• Permanent integration into neuronal membranes

Correct Answer: Intrinsic biogenesis, biocompatibility, and the ability to cross the BBB with low immunogenicity

Q14. Adsorptive-mediated transcytosis (AMT) at the BBB is most effectively promoted by:

• PEGylation to increase hydrophilicity
• Cationization to increase electrostatic interactions with the endothelial glycocalyx
• Incorporating RGD motifs for integrin binding
• Reducing particle size below 5 nm

Correct Answer: Cationization to increase electrostatic interactions with the endothelial glycocalyx

Q15. Which experimental technique best quantifies BBB permeability independent of systemic clearance and metabolism?

• Brain microdialysis following intravenous dosing
• Cerebrospinal fluid sampling after intrathecal dosing
• In situ brain perfusion with controlled vascular input
• Whole-body autoradiography at terminal time points

Correct Answer: In situ brain perfusion with controlled vascular input

Q16. The glymphatic system facilitates brain waste clearance primarily via:

• Endothelial fenestrations in brain microvessels
• Perivascular CSF–interstitial fluid exchange facilitated by AQP4 in astrocytic endfeet
• Bulk flow through neuronal axons
• Active transport by microglial pumps

Correct Answer: Perivascular CSF–interstitial fluid exchange facilitated by AQP4 in astrocytic endfeet

Q17. Which excipient is commonly used to enhance nasal residence time and permeability for nose-to-brain formulations?

• Polyethylene glycol (PEG)
• Poly(lactic-co-glycolic acid) (PLGA)
• Chitosan
• Polyvinyl alcohol (PVA)

Correct Answer: Chitosan

Q18. Why is the enhanced permeability and retention (EPR) effect unreliable for nanoparticle delivery to brain tumors?

• Brain tumors have uniformly fenestrated vasculature
• The blood–tumor barrier is heterogeneous with residual tight junctions and active efflux, limiting accumulation
• Nanoparticles cannot circulate systemically long enough
• EPR is blocked by the choroid plexus

Correct Answer: The blood–tumor barrier is heterogeneous with residual tight junctions and active efflux, limiting accumulation

Q19. Which targeting peptide, derived from rabies virus glycoprotein, is used to enhance brain delivery via nicotinic acetylcholine receptor interaction?

• TAT peptide
• Penetratin
• RVG29
• Angiopep-2

Correct Answer: RVG29

Q20. A critical safety consideration during FUS-mediated BBB opening is the risk of:

• Irreversible endothelial apoptosis at all clinical acoustic pressures
• Microhemorrhages, mitigated by controlling microbubble dose and real-time cavitation monitoring
• Immediate widespread neuronal necrosis
• Permanent disruption of astrocytic endfeet

Correct Answer: Microhemorrhages, mitigated by controlling microbubble dose and real-time cavitation monitoring

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