INTRANASAL LEPTIN FOR

PHARMACOLOGICAL PURPOSES
Mentor-
Dr. Shweta Dang

Presentation by-
Riya Sharma (15101017)
 Leptin: An important hormone
• Adipose-derived protein, consisting of 167 amino acid residues,
encoded by the Ob gene on chr. 6.

• Lack of leptin in humans leads to neuroendocrine dysfunction,

neurodegenerative disease, stroke, and cognitive impairment.

• Leptin enters the brain through saturable, passive transport across

BBB Cardiovascular, nervous, immune, and reproductive systems
dysregulated when leptin signaling pathways are compromised.
 Importance of Leptin in CNS Diseases:

• Leptin receptors (ObRs) -abundant in the hypothalamus and activate several

intracellular signaling events (JAK/STAT, MAPK, PI3K, and mTOR pathway).

• leptin treatment helps in curing diseases such as AD, PD, depression, and
acute cerebral I/R injury.
Absorption of Leptin in Mouse

• It was observed that the

bioavailability of leptin in
blood for a very long time
was poor.

• Hence intravenous
delivery of leptin is not
feasible.

Source: https://www.endocrineconnections.org
 Intranasal Delivery of Leptin:

• Takes advantage of nerves in upper

portion of nose, which leads to brain.

• Drugs can travel along and through

these nerves bypassing the BBB.

(img source: twincities.com)

.
Advantages of intranasal delivery of leptin
• Large nasal mucosal surface area for dose absorption
• Rapid drug absorption via highly vascularized mucosa
• Rapid onset of action
• Ease of administration, non-invasive
• Bypass the BBB
• Avoidance of gastrointestinal tract
• Improved Bioavailability
• Direct transport into systemic circulation and CNS is possible
• Lower dose/reduced side effects
CASE STUDY

• Recombinant leptin (0.5 mg/rat) was administered into the bilateral nasal spaces
of rats. Changes in serum immunoreactive leptin (IRL) and cerebrospinal fluid
(CSF)-IRL concentrations after i.n. leptin administration were compared with the
intraperitoneal (i.p.) administration.

• the effectiveness of i.n. administration on the transport of leptin into the

cerebroventricular space and brain of rats was demonstrated.
 Result
• CSF-IRL concentrations in non-leptin-
treated rats were about 400 pg/ml.

• The i.p. administration of 0.5 mg leptin

increased CSF-IRL concentrations about
twice as high as in non-leptin-treated
rats.

• In contrast, i.n. administration of 0.5 mg

leptin significantly increased CSF-IRL
concentrations to about three times
higher than in non-leptin-treated rats.
Changes in CSF IRL concentrations 60 min after i.p. and
i.n. administration of 0.5 mg leptin
CONCLUSION

Intranasally administered leptin is more effective than intraperitoneal

administration and hence can work as a potential drug for treatment of various
neurodegenerative diseases like AD, PD, etc.
Future perspective
• Use of nanotechnology in delivering drugs to the brain is a promising
area and can package the proteins or enhance the permeation of the
compounds across nasal mucosa.

• Detailed experiments describing the exact transport of proteins and

peptides from the nasal cavity to the brain should be explored in the
animal models.
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