Nasal & Otic Delivery

Question 1

Why deliver drugs to the nose - 5

Answer 1

1. Large absorption area
2. Rich in SC blood vessels
3. Rapid drug absorption & fast action - not only for local therapy but also system
4. Avoids first-pass metabolism
5. Easy to administer

Question 2

Turbinates - 3

Answer 2

1. Warm & humidify air that passes through the nasal cavity.
2. Swell & contract to control airflow - one swells while the other contracts cycling through a ‘nasal cycle’.
3. Helps detect pathogenicity of inhaled particles.

Question 3

Ciliated epithelium

Answer 3

Goblet cells accompany to produce mucus that traps dirt/particulates, the cilia than move in a wavelike motion to push them out of the nose

Question 4

Mucus production - 3

Answer 4

1. Mostly water, some salts, lipids & proteins such as mucins.
2. Mucins are high MW and are released by goblet cells to trap particulates.
3. Can bind to drugs either electrostatically or through H-Bonds, which can affect the drugs behaviour.

Question 5

3 routes of nasal delivery

Answer 5

Drug Deposition - Drug deposited in nasal cavity,

Mucosal Absorption - Drug absorbed across the mucosa

Mucociliary Clearance - Movement of the mucus layer to the nasopharynx.

Question 6

Mucosal absorption - 2

Answer 6

1. Drug deposition affects how drug interacts with mucous layer.
2. Type & size determines if transcellular or paracellularly absorbed.

Question 7

Mucociliary clearance - 3

Answer 7

1. Mucus clearing ever 10-20mins determines how long a formulation is retained in cavity before expelled by mucus.
2. Drugs on ciliated regions are cleared immediately.
3. Drugs on non-ciliated regions move slowly

Question 8

Reducing mucociliary clearance - 2

Answer 8

1. Reduced through mucoadhesives
2. They increase viscosity by adding polymers & gels can improve retention time of drugs.

Question 9

Nose: Olfactory bulb delivery route - 2

Answer 9

1. Avoids systemic clearance & first pass metabolism.
2. Effectively no BBB.

Question 10

Problems & solutions to nasal drug delivery - 5

Answer 10

1. Drug permeability: permeation enhancers, controlled delivery system, colloidal drug carriers
2. Mucociliary clearance: mucoadhesives (increasing viscosity, adding polymers, using gel formulations)
3. Enzymatic degradation: protective coatings (nanocarriers)
4. Toxicity: improved formulations
5. Small volume: [increasing] could lead to toxicity therefore optimization needed

Question 11

Improving drug permeability in the nose - 2

Answer 11

1. Permeation enhancers, controlled delivery system & colloidal drug carriers.
2. Decrease lipid bilayer integrity causing increased membrane fluidity, promoting transcellular permeation of drugs.

Question 12

Tympanic membrane healing - 3

Answer 12

1. Cell migration closes the epidermis, begins due to flooding of cells & growth factors.
2. The fibrous layer is reconstructed.
3. Maturation occurs with long term remodelling & reorganisation using stronger collagen fibres to restore tensile strength.

Question 13

Phonografts& tympanic membrane - 2

Answer 13

1. Procedure insertion into ear canal
2. Stimulates self healing

Question 14

Inner ear - 4

Answer 14

1. Cochlear - Auditory organ
2. Vestibular Systems - Organ of balance
3. Contains hair cells to act as sensory receptors for hearing & balance.
4. Mechanoreceptors with cilia at differing heights able to interpret frequencies of sound via movement which generate nerve impulses transmitted to the brain.

Question 15

Middle ear - 2

Answer 15

1. Transmit sound from air to fluid filled cavity by amplifying vibrations from TM.
2. Eustachian tube/ auditory tube - drugs are administered in the middle ear to be cleared.

Question 16

Drugs across tympanic membrane - 2

Answer 16

1. Non-invasive: Diffusion to middle ear, e.g. hydrogels, chemical permeation enhancers, nanocarriers & peptides
2. Invasive: Injection/device crossing tympanic membrane e.g. Drug delivery system in middle ear allows drug diffusion to inner ear.

Question 17

4 non-invasive delivery systems

Answer 17

1. Hydrogels stay on TM to provide a prolonged released.
2. Chemical Permeation Enhancers increases flux across barriers
3. Nanocarriers - method of deposition, used in combo with lipid softeners & surfactants.
4. Peptides - Can be used to cross barriers.

Question 18

Invasive drug delivery - 4

Answer 18

1. Hydrogels - Avoiding clearance via eustachian tube lets deeper penetration
2. Nanoparticles - Surface modifications can enhance penetration properties
3. Ultrasound - Induces microbubbles to drive drugs through round window in inner ear
4. Pump/Catheter - Programmable & implantable deliver devices allow for precise control of drug release

Question 19

Ototoxicity - 3

Answer 19

1. Adverse reaction to drugs affecting inner ear or auditory nerve - via cell degradation.
2. Affects cochlear/vestibular system.
3. Can cause tinnitus, hearing loss, vertigo & dizziness.

Question 20

Challenges to otic drug delivery - 5

Answer 20

1. Patients prefer oral drug administration
2. Difficult application
3. Cost
4. Potential pain
5. Variable [drug] across the TM