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Advanced Drug Delivery > CNS Delivery > Flashcards

CNS Delivery Flashcards

1
Q

What are the CNS barriers?

A

BBB and blood CSF barrier

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2
Q

What is the function of the BBB?

A

Create ionic homeostasis

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3
Q

What is the blood CSF barrier?

A

Interface between choroid plexus and CSF
CSF secreted across choroid plexus epithelial cells into brain

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4
Q

From where is cerebral spinal fluid secreted from?

A

Choroid plexus

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5
Q

What are the characteristics of the blood brain barrier?

A

Tight junctions between endothelial cells lining capillaries in the brain. tight junctions restrict paracellular aqueous pathway
Capillaries are covered by astrocytes

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6
Q

What are the functions of the blood brain barrier?

A

-Ion regulation/homeostasis- potassium is higher and plasma than the CSF
-Segregation of neurotransmitters- control and peripheral transmitters are kept separate
-supplement the brain with nutrients- not albumin or thrombin
-protection from neurotoxins- endogenous metabolites or proteins, bacteria or viruses

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7
Q

How do drugs cross the blood brain barrier?

A

-Paracellular aqueous pathway is limited because hydrophilic drugs are kept out
-trans cellular lipophilic diffusion
-Carrier mediated transport
-receptor mediated endocytosis- for large molecules
-Active efflux transport- P – glycoprotein- main barrier

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8
Q

How is blood CSF a barrier?

A

Choroid plexus has outer epithelial cells with microvilli

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9
Q

how do substances pass the blood brain barrier?

A

Brain cells very close to capillaries and diffusion distance to neurons are short

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10
Q

How substances enter the brain via the blood CSF barrier?

A

Across the choroid plexus via CSF

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11
Q

What are examples of direct CNS delivery?

A

-intra cerebral, intraventricular, intrathecal

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12
Q

What are the advantages of intracerebral and intraventricular delivery?

A

-Can deliver higher concentration by direct injection with reduced peripheral concentrations
-bypass the blood brain barrier
-Can insert cerebral implant for controlled release

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13
Q

What are the disadvantages of cerebral and interventricular delivery?

A

-highly invasive- need burr holes (drill), craniotomy
- limited brain distribution needs to be potent with narrow focal area

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14
Q

What is intrathecal delivery?

A

Injection into intrathecal space that holds spinal fluid

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15
Q

What is the advantage of intrathecal delivery?

A

Less invasive

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16
Q

What are the disadvantages of intrathecal delivery?

A

Drug spreads distally along spinal cord leading to ataxia (loss of movement of muscles)
No controlled release as doesn’t accumulate in brain parenchyma

17
Q

What are examples of nondirect CNS delivery?

A

-intravenous, intra arterial/entry carotid, transnasal

18
Q

When would intra arterial delivery be used?

A

For enhanced intra tumoural concentrations in combination with blood brain barrier disrupting agents (hypertonic mannitol)

19
Q

What are the advantages of transnasal delivery?

A

Bypass the blood brain barrier (olfactory region has cells extending into cranial cavity)
Non-invasive

20
Q

What are the disadvantages of transnasal delivery to the brain?

A

Not all drug absorbed- some drops down throat and swallowed

21
Q

What are examples of blood brain barrier disruption?

A

Opening tight junctions via-
-Hypertonic mannitol- high osmotic pressure shrink cells
-Ultrasound/electromagnetic radiation- temperature or ultrasonic waves create lesions

22
Q

What other methods can be used to increase CNS drug absorption?

A

-chimeric peptides
-cationic proteins
-Liposomes
-Nano particles
-Pro drugs

23
Q

How do chimeric peptides increase CNS absorption ?

A

Drug is covalently bond to vector to form transportable fused molecule

24
Q

How do catatonic proteins increase CNS absorption?

A

Increases positive charge on drug molecule by modifying free carboxyl groups
Which interact with anionic functional groups on brain surface

25
Q

How do lipsomes improve CNS delivery?

A

Liposomes coated in PEG have longer residence time

26
Q

How do nano particles improve CNS delivery?

A

They are small ,have better solubility, enter via endocytosis
Are biodegradable

27
Q

What is an example of a pro drug used to deliver CNS therapeutics?

A

L-Dopa
Precursor of dopamine used in Parkinson’s
Parkinson’s is a result of dopamine depletion in basil ganglia
Dopamine can’t be used as it is hydrophilic and water soluble .

28
Q

What is Carbidopa?

A

Given alongside levo dopa To break it down and prevent peripheral metabolism

Advanced Drug Delivery (15 decks)

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