The document summarizes nose-to-brain drug delivery. It discusses how the nasal route can bypass the blood-brain barrier to deliver drugs non-invasively to the central nervous system. It covers the advantages and limitations of nasal delivery. The nasal anatomy and mechanisms of nose-to-brain transport are described. Various excipients, formulations, and evaluation methods are also outlined. The conclusion states that understanding the nasal and blood-brain barrier anatomy is important for developing effective nasal formulations to cross the blood-brain barrier and target the brain.

1. GE-511- SEMINAR
TOPIC – NOSE TO BRAIN DRUG DELIVERY
Presented By:
Harshad Arvind Takate
First Semester
Reg No. : PTF/2022-03/026

2.  INTRODUCTION
 ADVANTAGES
 LIMITATIONS
 NASALANATOMY AND PHYSIOLOGY
 MECHANISM OF NOSE TO BRAIN DRUG DELIVERY SYSTEM
 EXCIPENTS USED IN NASAL FORMULATION
 INTRANASAL BRAIN TARGETING NDDS
 NASAL FORMULATIONS
 EVALUATION OF NASAL DRUG DELIVERY SYSTEM
 CONCLUSION
 REFERENCES
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3. INTRODUCTION
1. Blood Brain Barrier (BBB) maintains the CNS homeostasis and restricts many toxic material from
entering into the brain
2. BBB is the major obstacle to the delivery of therapeutics into the CNS
3. BBB Consists of astrocytes, pericytes and tight junction with trans-endothelial electrical resistance
of 1500-2000Ω 𝒄𝒎𝟐
4. Nasal route can provides a non invasive method to bypass BBB and BCSFB, can be used to deliver
synthetic as well as biologics like peptides, proteins, viral vectors and even stem cells
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4.  Can be used to deliver synthetic as well as biologics like peptides, proteins, viral vectors and
even stem cells
 Non-invasive/reduced infection risk from application/low risk of disease transmission
 Rapid drug absorption and quick onset of action in the CNS can be achieved
 Better patient compliance. Self-administration
 Bioavailability of larger molecules can be improved using absorption enhancers
 Chemotherapeutic agents can be directly given into the CNS hence reducing the peripheral
side effects
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5. LIMITATIONS
 Low pH of nasal epithelium ( mostly weak acidic drug can be delivered with pH range of
4.5-6.5)
 interindividual variability
 Pathological condition of nose inhibit drug absorption
 Muco-ciliary clearance
 Pseudo first pass effect( nasal CYP450, peptidase, protease)
 Low volume can be delivered (25-200μL)
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6. NASAL ANATOMY AND PHYSIOLOGY
1. Nasal cavity is lined with hair and secretion layer.
2. The total volume of human nasal cavity is 15 to 20 ml and surface area is 150 cm2
3. The nasal cavity is divided into 4 areas and the name are:
1. Nasal vestibule
2. Atrium
3. Respiratory area
4. Olfactory area
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(1)
(4)
(2)
(3)

7. MECHANISM OF NOSE TO BRAIN DRUG DELIVERY SYSTEM.
There are main two pathway for absorption of drug from nasal
epithelium
Transcellular pathway Paracellular pathway
Passive diffusion.
Active diffusion.
Fasciculated diffusion
.
Influx or efflux of
anions.
Between tight
junction of nasal
epithelial cell.
Paracellular route - Hydrophillic drug.
Transcellular route – Lipophillic drug.
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Figure : mechanism of nose to brain drug delivery system.
Jeffrey J. Lochhead, Robert G. Thorne, Intranasal delivery of biologics to the
central nervous system, Advanced Drug Delivery Reviews, Volume 64, Issue
7,2012,Pages 614-628,

8. 1) OLFACTORY NERVE PATHWAY
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2) TRIGEMINAL NERVE PATHWAY
pons

9. ELIMINATION
Nasal cavity
organs
Olfactory region
Brain
CSF
BLOOD
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10. EXCIPIENTS USED IN NASAL FORMULATION
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11. 11
Nanocarriers
1)Nanoparticles
i. Polymeric NPs
ii. Peptide surface modified NPs
iii. Lipid based NPs
2) Nano emulsions
3)Micelles
4)Nanogels
5)Liposomes
6)Nanoemulsomes
Microcarriers

12. NASAL FORMULATIONS
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Name of
product
company Dosage
form
Active ingredient disease
OnzetraTM Optinose powder Sumatriptan Migraine
Zomig Astra Zeneca pharmaceuticals Nasal spray Zolmitriptan Acute migraine
Narcan Adapt Pharma Nasal spray Naloxone hydrochloride Opioid overdose

13. EVALUATION OF NASAL DRUG DELIVERY SYSTEM
• In vitro diffusion studies
• In vivo nasal absorption studies
• Ex vivo nasal perfusion models
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14. CONCLUSION
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For the development of nasal formulation, one has to understand the function of
blood brain barrier and the unique structure of respiratory region and the olfactory
region of nose
Approaches for nasal drug delivery like nanoemulsion is use for nasal
formulation which leads to cross blood brain barrier and specific targeting in
brain
Any delivery systems developed should have no significant impact, short or long
term, on the functions of the brain

15. REFERENCES
1) Patel Z ., Patel B ., Patel S., et.al., Nose to Brain Targeted Drug Delivery bypassing the Blood-
Brain Barrie: An Overview , Drug Invention Today., 2012 , 4(12), 610-615
2) Jeffrey J. Lochhead, Robert G. Thorne, Intranasal delivery of biologics to the central nervous
system, Advanced Drug Delivery Reviews, Volume 64, Issue 7,2012,Pages 614-628,
3) Jeong SH, Jang JH, Lee YB. Drug delivery to the brain via the nasal route of administration:
exploration of key targets and major consideration factors. Journal of Pharmaceutical
Investigation. 2022;1–34
4) Khan AR, Liu M, Khan MW, Zhai G. Progress in brain targeting drug delivery system by nasal
route. Journal of Control Release.,2017, 268, 364-389
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