NASAL MUCOSA

PRESENTED BY-DURGESH JHAPALLAVI R. WADKE

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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

• References2

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

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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.

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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

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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 andii. Lamina propria

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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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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 8

Contd..Regions of the Nasal Cavities• Each nasal cavity consists:i. the nasal vestibuleii. 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.

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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.

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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 andii. an upper gel layer.

• The pH of nasal secretion is 5.5-6.5 in adults and 5.0-6.7 in infants 11

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

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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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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

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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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 16

•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- invasive17

CONTD..

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 18

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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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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PATHWAY

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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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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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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 24

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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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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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

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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 systemsRahamatullah 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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