Nose to Brain Targeted Drug Delivery.pptx

NOSE TO BRAIN TARGETED DRUG DELIVERY BYPASSING BBB.

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

2. CONTENTS INTRODUCTION ADVANTAGES LIMITATIONS NASAL ANATOMY 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 2

3. INTRODUCTION Blood Brain Barrier (BBB) maintains the CNS homeostasis and restricts many toxic material from entering into the brain BBB is the major obstacle to the delivery of therapeutics into the CNS BBB Consists of astrocytes, pericytes and tight junction with trans-endothelial electrical resistance of 1500-2000 Ω 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   3

4. ADVANTAGES 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 4

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 (25-200 μ L) 5

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 6 (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. 7 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 8 2) TRIGEMINAL NERVE PATHWAY pons

9. ELIMINATION Nasal cavity organs Olfactory region Brain CSF BLOOD 9

10. EXCIPIENTS USED IN NASAL FORMULATION Mucoadhesive Excipients (Carbopol, CMC, Chitosan ) Absorption Enhancers (Laureth 9 sulphate, CD, Bile salts, surfactants) Preservatives (Chlorobutol, hydroxybenzoate, chlorocresol) Surface protein ( cell penetrating peptides- LMWP) Enzyme inhibitors ( Camostat ) Modulators of tight junction ( chitosan ) 10

11. INTRANASAL BRAIN TARGETING NDDS 11 Nanocarriers 1)Nanoparticles Polymeric NPs Peptide surface modified NPs Lipid based NPs 2) Nano emulsions 3)Micelles 4)Nanogels 5)Liposomes 6)Nanoemulsomes Microcarriers

12. NASAL FORMULATIONS 12 Name of product company Dosage form Active ingredient disease Optinose powder Sumatriptan Migraine Zomig Astra Zeneca pharmaceuticals Nasal spray Zolmitriptan Acute migraine Narcan Adapt Pharma Nasal spray Naloxone hydrochloride Opioid overdose Name of product company Dosage form Active ingredient disease 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 13

14. CONCLUSION 14

15. REFERENCES 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 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, 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 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 15

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