Brain Targetting through Intranasal Route

A 10 page paper on what I've been suggesting the last couple of years.
http://sphinxsai.com/2013/OD/PharmOD13/pdfphamOD2013/PT=01%281441-1450%29OD13.pdf

Abstract:

The blood brain barrier (BBB) represents one of the strictest barriers of in vivo therapeutic drug delivery. The barrier is an restricted exchange of hydrophilic compounds, small proteins and charged molecules

between the plasma and central nervous system (CNS). For decades, the B

BB has prevented the use of many therapeutic agents for treating Alzheimer’s disease, stroke, Brain tumour, head injury, depression, anxiety and other CNS disorders. Various techniques and Attempts were made to deliver the drug across the BBB such as modification of therapeutic agents, Altering the barrier integrity, carrier mediated transport, invasive techniques,etc. However, opening the barrier by such means allows entry of toxins and undesirable molecules to the CNS, resulting in potentially significant damage. Many advanced and effective approaches to brain delivery of drugs have emerged in recent years. Intranasal drug delivery is one of the focused delivery options for brain targeting, as the brain and nose compartments are connected to each other via the olfactory route and via peripheral circulation. In this review we discuss the effects of microspheres and other Bioadhesive drug delivery systems on nasal drug absorption. Drug delivery systems, such as microspheres, liposomes, Microemulsion, Nano emulsion and gels have been demonstrated to have good Bioadhesives characteristics and that swell easily when in contact with the nasal mucosa.

Introduction:

Nasal drug delivery is used for various kinds of diseases. It is not only used recently but it recognised form oftreatment in the Ayurvedic system of Indian medicine called “nasal karma”.

1. in recent year growing interest has focused on the use of nasal route for systemic delivery & Brain targeting. Drug which undergoes first pass

metabolism to avoid this and increases there bioavailabili

ty of drug nasal route is preferred

2.  It is useful for the drug which are active at low doses & show very less oral bioavailability such as Protein and peptide

3. central nervous system diseases such as Epilepsies, meningitis, migraine, Parkinson diseases, Alzheimer diseases has difficulty In targeting because of the transport through Blood Brain Barrier

4.  From literature it shows that such diseases can be treated by transporting exogenous material to brain by nose or it’s an effective route bypassing BBB

5. The result of concentration time Profile of intranasal administration drug is similar to the Intravenous route

6.  The pathway employed for the delivery of particular drug from the nose to brain is highly dependent on various factors, such as existence of specific receptor on the olfactory neurons, the lipophilicity and molecular weight of the drug

7.  Intra nasal delivery is non invasive& painless delivery and it does not required sterile preparation & it is easy method of drug administration for patient or physician. The nasal route offers improve delivery for “non

-

Lipinski” drug

8.  Lipophilic drug can easy cross BBB by traveling throw Transcellular

pathway. Hydrophilic drug transport throw paracellular pathway so they have very less chance to pass BBB.

Polar molecule have very less chance to pass from respiratory region to blood stream so they have some chances to reach brain by passing or travelling throw olfactory mucosa in nose

9.  Although many novel nasal product for systemic delivery on various diseases are launched in market but still no drug exploiting the nasal route to treat CNS diseases. Development of drug delivery throw nose to enable rapid & effective concentration in Brain is challenges for Researchers

7. Advantages of nasal drug delivery:

10,11,12

1)  Drug degradation that is observed in the gastrointestinal track is absent.

2) Hepatic first pass metabolism is avoided.

3) The nasal bioavailability for smaller drug molecule is good.

4) Studies so far indicates that the nasal route is an alternative to parenteral route, especially for protein’sand peptide drug.

5) Convenient for the patient especially for those on long term therapy, when compared with parenteral medication.

6) Polar compound exhibiting poor oral absorption may be particularly studies for this route of delivery.

7) Large nasal mucosa surface area for dose absorption.

8) Ease of administration, non-invasive.

9) Lower dose reduced side effects.

10) Self-administration