This document discusses strategies for targeted drug delivery to the brain. It begins by introducing the challenges of drug delivery across the blood-brain barrier (BBB), blood-cerebrospinal fluid barrier, and blood-tumor barrier. It then describes various approaches researchers have developed to enhance central nervous system drug delivery, including using lipophilic analogs, prodrugs, carrier-mediated delivery, and vectors. The document also discusses methods for temporary disruption of the BBB, such as using hypertonic solutions or biochemical agents. Promising strategies highlighted include liposomes, nanoparticles, implantable drug reservoirs, and systems based on enzymatic activation. The overall goal is to develop treatments for diseases of the brain and central nervous system.

1. Brain Specific Delivery
BY: Mr. Kiran Ankushrao Tengse
M. Pharm 1st Year
University Department of Pharmaceutical Sciences , Nagpur

2. Content
 Introduction
 Blood Brain Barrier
 BCSFB and Blood tumor barrier
 Strategies for enhanced CNS drug delivery
 Approches for disruption of BBB
 Promising strategies for brain targeting
 Conclusion
 Referencs

3. Introduction
 Brain targeting is targeting of the drug to the specific site of the brain
 Brain targeting is neccessory in the treatment of the psychosis, affective disorder
such as depression ,mania, anxieties, seizures, Parkinson’s disease, alzhiemers
disease, pain and brain tumors.
 However drug generally do not enter the brain .
 The chief challenge to the CNS delivery is BBB which restricts the access of drug
to the brain .
 So that in order to target the brain for drug delivery , knowledge about BBB should
be there.
 Other important barriers are Blood-CSF barrier and Blood-Tumor barrier.

4. 1.Blood Brain Barrier
 Brain capillaries consists of endothelial cells which are joined one another by
continuous tight intercellular junctions.
 Provided the presence of the special cells on the base of endothelial membrane which
forms envelope around brain capillaries .
 This barrier is called as the Blood Brain Barrier .

5.  Due to such structure of the BBB the intercellular [paracellular] passage is
blocked .
 So that drugs pass through transcellular route.
 Thus the drug gain access to the brain eighter by one of the pathway
1.Passive diffusion :
mol. Wt. less than 700 Dalton
high o/w partition coefficient
2.Active transport :
essential nutrients i.e. sugars and amino acids
structurally similar molecules

6. 2.Blood-CSF barrier:
choroid plexus and arachnoid membrane act together barrier between blood and
CSF .
3.Blood tumor barrier:
Drug delivery to the intracranial is more challenging when target is CNS tumor
because
-as tumor grows vascular suface area decrease
-at the same time intracapillary distance increases so greater diffusion of drug
requires.

7. Strategies for enhanced CNS drug delivery
 1. Lipophilic analogue :
As the all drugs which crosses BBB follows transcellular pathway .i.e. only
highly soluble drugs can cross BBB easily.
So Hydrophobic analogue of the small water loving drugs can easily penetrate BBB.
Ex. Diacetyl derivative of Morphine crosses BBB hundred times more than its
parent drug just being more lipid loving.
2.Prodrug :
Prodrugs are prepared to improve the physical and chemical properties like
membrane permeability and water solubility.

8. 3.Chemical drug delivery :
In this strategy targeting is based upon the predictable enzymatic activation.
Site specific delivery is obtained through the multistep enzymatic or chemical
transformation.
by chemical transformation two types of the moieties introduced
Targeting Function modifier
which acts as the lipophililizer
Ex. Trigonelline targeting by the oxidoreductase enzymes .

9. 4. Carrier mediated Drug delivery:
Presence of the endogenous carriers are responsible for the targeting of
nutrients and peptides to the brain.
Ex.
a] Hexose transfer system for glucose and mannose.
b]amino acid transport system for amino acids.
c]choline transport system for choline and thiamine.
d]Nucleoside transport system for purine bases such as adenine and guanine
5.Vector mediated drug delivery:
In this the non transportable drug is conjugated to the blood brain barrier
transport vector through the linker .

10. Approches for disruption of BBB
1.Osmotic BBB disruption :
Intracaratoid injection of the inert hypertonic solution such as mannitol cause
the opening of the tight junction of the endothelial cells for several hours.
For tumor cells –25% permeability increase
For normal brain cells –10% permeability increases.
2. Biochemical BBB disruption :
Intracaratoid infusion of the leukotriene C4 opens the brain tumor capillaries
selectively.
novel observation in that is normal brain cells remains unaffected .

11. Promising Strategies for Brain targeting
1.Liposome targeting to brain
2.Nanoparticles for drug delivery across BBB
3.Implantation within the brain by
-genetically engineered cells secreting drug
-Polymeric matrix
-reservoir containing the drug
4.Chemical delivery systems based on the predictable enzymatic activation .
5.Chimeric peptide systems ,wherein a non-transportable drug is conjugated to a
BBB transport vector.

12. Conclusion
 Treatment of the CNS diseases is challenging because of the barriers like BBB,
BCSFB, Blood tumor barrier .
 For the brain targeting drug should be highly lipoidal in nature.
 Treatment off CNS diseases is complex.
 Recent development in the brain delivery overcome these barriers at great extent.

13. References
1.N.K. Jain, Controlled and Novel Drug Delivery , CBS Publishers and Distributors
,New Delhi , First edtion 1997.
2.D.M. Brahmankar and Sunil B. Jaiswal , Biopharmaceutics and Pharmacokinetics a
treatise, Vallabh prakashan , Second edition 2012.

14. THANK YOU…!!!