This presentation deals with the study of anatomy and physiology of nasal mucosa and the potential advantage of nasal administration of therapeutic agents...

1. NASAL MUCOSA
PRESENTED BY-
DURGESH JHA
PALLAVI R. WADKE
1

2. OVERVIEW
• Introduction to Nasal Mucosa
• Anatomy of Nasal Mucosa
• Nasal cavity
• Blood supply to nasal cavity
• Physiology of Nasal Mucosa
• Advantages and Disadvantages of Nasal Mucosa
• Pathways of Absorption
• Enhancement in absorption
• References
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3. INTRODUCTION TO NASAL MUCOSA
• The anatomy and physiology of the nasal
passage indicate that nasal administration has
potential practical advantages for the
introduction of therapeutic drugs into the
systemic circulation via nasal route
• Drugs can be rapidly absorbed through the
highly vascular nasal mucosa, and they also
avoid degradation in the gastrointestinal tract
and first-pass metabolism in the liver
3

4. CONTD..
• In the last decade, there has been much interest in the
nasal route for delivery of drugs to the brain via the
olfactory region in order to circumvent the blood brain
barrier (BBB)
• It has been suggested that there is free communication
between the nasal submucosal interstitial space and
the olfactory perinueronal space which appears to be
continuous with a subarachnoid extension that
surrounds the olfactory nerve.
4

5. RATIONALE FOR NASAL DRUG DELIVERY
• A relatively large surface area (epithelium covered with microvilli)
available for drug absorption
• A thin, porous and very vascularized epithelium with high total
blood flow per cm3, which ensures rapid absorption and onset of
therapeutic action
• A porous endothelial basement membrane
• The direct transport of absorbed substances into the systemic
circulation (or even directly into the CNS), thereby avoiding the
First-pass effect attendant with peroral drug administration
• Lower enzymatic activity compared with the GIT and liver
• Amenable to self-medication, which increases patient compliance
5

6. ANATOMY OF NASAL MUCOSA
• The mucosa, or mucous
membrane, is a type of
tissue that lines the nasal
cavity. Mucous membranes
are usually moist tissues
that are bathed by
secretions such as in the
nose.
• Mucosa consists of two
layers:
i. Epithelial layer and
ii. Lamina propria
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7. CONTD…
• The nasal mucosa, also called respiratory mucosa,
lines the entire nasal cavity, from the nostrils (the
external openings of the respiratory system) to the
pharynx (the uppermost section of the throat)
• The respiratory mucosa shows a thickness of 0.3–5
micrometer
• The external skin of the nose connects to the nasal
mucosa in the nasal vestibule
• A dynamic layer of mucus overlies the nasal
epithelium (the outermost layer of cells of the nasal
mucosa)
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8. NASAL CAVITY
• The nostrils are a
pair of nasal
cavities divided by a
nasal septum ; their
total volume is
approximately 15 cc
,with a total surface
area of 150 cm2
• The nasal passage
runs from nasal
vestibule to
nasopharynx
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9. Contd..
Regions of the Nasal Cavities
• Each nasal cavity consists:
i. the nasal vestibule
ii. the respiratory region possess lateral walls:
 inferior turbinates
 Middle turbinates
 Superior turbinates
iii. the olfactory region
These folds ensures the large surface area of nasal
cavity.
9

10. Contd…
1. Vestibular region having an area of 10 to 20
sq.cm and is situated just inside the nostrils.It is
covered with stratified, keratinised and squamous
mucosal epithelium.
2. Respiratory region is the largest part of the
nasal cavity, has a rich neurovascular supply, and is
lined by respiratory mucosal epithelium composed
mainly of ciliated and mucous cells.
3. Olfactory region is small, is at the apex of each
nasal cavity, is lined by olfactory epithelium, and
contains the olfactory receptors.
10

11. NASAL SECRETION AND MUCUS LAYER
• Nasal secretions are secreted
by goblet cells, submucosal
glands and transudate from
plasma.
• Mucus, visco-elastic fluid,
covers the respiratory part of
the nasal cavity.
• Mucus blanket is made of two
layers,
i. a lower sol layer and
ii. an upper gel layer.
• The pH of nasal secretion is
5.5-6.5 in adults and 5.0-6.7 in
infants 11

12. BLOOD SUPPLY TO NASAL MUCOSA
Include vessels that originate
from both the internal and
external carotid
arteries:
• Vessels that originate from
branches of the external
carotid artery include the
sphenopalatine, greater
palatine, superior labial,
and lateral nasal arteries;
•Vessels that originate from
branches of the internal
carotid artery are the
anterior and posterior
ethmoidal arteries.Veins:
Veins draining
12

13. PHYSIOLOGY NASAL CAVITY
• The nasal cavity has an important protective
function in that it filters, warms, and humidifies
the inhaled air before it reaches the lower airways
• Any inhaled particles or microorganisms are
trapped by the hairs in the nasal vestibule or by the
mucus layer covering the respiratory area of the
nasal cavity
• Due to the mucociliary clearance mechanism, layer
will gradually carry such particulates to the back of
the throat, down the esophagus, and further into the
gastrointestinal tract
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14. MUCOCILIARY CLEARANCE
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• The function of the mucociliary clearance system
is to remove foreign substances and particles from
the nasal cavity, thus preventing them from reaching the
lower airway
• Nasal mucociliary clearance also largely determines the
absorption profile of nasal drug delivery, since the
residence time of drugs administered to the nasal cavity
is limited by mucociliary clearance
• Normal mucociliary transit time: 12- 15 min

15. Contd..
• Mucociliary clearance operates through the
action of ciliated cells lining the airway
epithelium
• The cilia beat in synchrony to continuously
move the mucous layer up the bronchial tree
• Inhaled particles become trapped in the moving
mucous layer and are transported into
progressively more proximal airways until, they
can be cleared from the bronchial tree
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16. ADVANTAGES NASAL ROUTE
• Ease of administration, non-invasive
• Large nasal mucosal surface area for dose
absorption
• Rapid drug absorption via highly-vascularized
mucosa
• Rapid onset of action
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17. •Avoidance of the gastrointestinal tract and first-
pass metabolism
•Low enzymatic activity
•Improved bioavailability
•Lower dose/reduced side effects
•Improved convenience and compliance
•Self-administration; non- invasive 17
CONTD..

18. DISADVANTAGES OF NASAL ROUTE
• Nasal cavity provides smaller absorption surface
when compared to GIT
• Relatively inconvenient to patients when compared
to oral delivery since there is possibility of nasal
irritation
• Pathological conditions such as cold and allergies
may alter nasal bioavailability significantly,
which can have an effect on the intended
pharmacological action
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19. ABSORPTION ACROSS THE NASAL
EPITHELIUM
• The four main absorption routes are
transcellular and paracellular passive
absorption, carrier-mediated transport and
absorption through transcytosis
• Transcellular passive diffusion is the main mode
of absorption for most drugs but, for large or
ionised molecules, the paracellular route can
provide an opportunity for absorption
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20. FACTORS AFFECTING NASAL
ABSORPTION
• Molecular wt- Absorption as Mol.Wt of drug
• Lipophilicity- Absorption as Lipophilicity of
drug
• pH of solution-pH should be optimum for
maximum absorption
• Drug concentration -The absorption of drug
through nasal route is increased as
concentration is increased
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21. PATHWAY
21

22. ENHANCEMENT IN ABSORPTION
• Following approaches used for absorption
enhancement :-
Use of absorption enhancers
Increase in residence time
Use of physiological modifying agents
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23. ENHANCEMENT IN ABSORPTION
 Use of absorption enhancers:-
Absorption enhancers work by increasing the rate at
which the drug pass through the nasal mucosa.
Various enhancers used are surfactants, bile salts,
chelaters, fatty acid salts, phospholipids,
cyclodextrins, glycols etc.
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24. ENHANCEMENT IN ABSORPTION
Various mechanisms involved in absorption
enhancements are:-
• Increased drug solubility
• Decreased mucosal viscosity
• Decrease enzymatic degradation
• Increased paracellular transport
• Increased transcellular transport
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25. ENHANCEMENT IN ABSORPTION
 Increase in residence time:-
• By increasing the residence time the increase in
the higher local drug concentration in the mucous
lining of the nasal mucosa is obtained
• Various mucoadhesive polymers like
methylcellulose, carboxymethylcellulose or
polyarcylic acid are used for increasing the
residence time
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26. ENHANCEMENT IN ABSORPTION
 Use of physiological modifying agents:-
• These agents are vasoactive agents and exert their
action by increasing the nasal blood flow
• The example of such agents are histamine,
leukotrienene D4, prostaglandin E1 and β-
adrenergic agents like isoprenaline and terbutaline
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27. REFERENCES
• Mucociliary Clearance and cystic Fibrosis ,Mark
R. Elkins, Peter T. P. Bye
• Nasal Administration of Compounds Active in
the Central Nervous System Exploring the
Olfactory Pathway, Maria dahlini
• Indian Journal of Pharmaceutical science,
January 1998
27

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•The biopharmaceutical aspects of nasal
mucoadhesive drug delivery, Michael Ikechukwu
Ugwoke, Norbert Verbeke, Renaat Kinget, Journal of
Pharmacy and Pharmacology ,JPP 2001, 53: 3±2
•Mucoadhesive drug delivery systems
Rahamatullah Shaikh, Thakur Raghu Raj Singh,
Martin James Garland, A David Woolfson, and Ryan
F. Donnelly, J Pharm Bioallied Sci. 2011 Jan-Mar;
3(1): 89–100

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