The brain is protected by a barrier of cells that tightly

regulates the transport of substances from the blood into this

organ. The essential protective function of the blood-brain

barrier (BBB) is also a red light for 98% of drug candidates

for the treatment of the central nervous system (CNS).

The capacity of a drug to cross the BBB is crucial, as several

major diseases require brain treatment. These include

neurodegenerative disorders such as Parkinson’s and Alzheimer’s,

but also CNS diseases, such as schizophrenia, epilepsy, and

bipolar disorder. Brain cancer, HIV, and some aspects of obesity

can also be included as pharmaceutical targets inside the brain.

pwvpswmpprht THRre

Inmunogenicity

Control THRre

Intravital two-photon microscopy images of the brains of mice after injection of naked QDs or QDs labeled with retro-enantio peptide.2

Protease Resistance

meritxell.teixido@irbbarcelona.org

Antibodies

TherapeuticPeptides

siRNA, DNA,..

Proteins

Small Molecules

Polimeric Nanoparticles

Two approaches with different strategic

points:

• Viral vectors for gene therapy, allow the

BBB transport of genetic material, even

the whole gene.

• Polimeric nanoparticles allow the BBB

transport of cDNA, antibodies, small

molecules or proteins and could be

interesting for their protection of the

cargo during the transport.

• It is important that the cargo is not

prematurely release until it reaches the

CNS.

Viral Vector* Malakoutikhah M.; Teixidó, M. ; Giralt, E. Angew. Chem.

Int. Ed. 2011, 50, 7998-8014.

Oller-Salvia, B. et al. Chem Soc.Rev. 2016, DOI: 10.1039/C6CS00076B

Carrier-mediatedtransport

Adsorptive-mediatedtransyctosis

Transcellularpassive diffusion

Receptor-mediatedtranscytosis

Inside the nanoambulances we can put different types of drug candidates

that could be interesting for the treatment of CNS disorders but can not

cross the BBB unaided.

Over recent years we have worked extensively on the

use of peptides as BBB-shuttles (or Nanoambulance

drivers) to carry drugs that cannot cross the BBB

unaided and therefore cannot reach the CNS.1

Patent: E. Giralt and M. Teixidó PCT/ES2007/000499; WO/2008/025867-

WO-ES-USA.

Publication: Diketopiperazines as a tool for the study of transport across

the blood-brain barrier (BBB) an their potencial use as BBB-shuttles.

Teixidó, M.; Zurita, E.; Malakoutikhah, M.; Tarrago T.; Giralt, E. JACS,

2007, 129, 11802-11813.

X2

N

N

O

O R1

R3

R2X1

Small Molecules

Small Molecules

(N-metil-Phe)x-CONH2

Publications:

* Malakoutikhah, M. et al. J. Med. Chem. 2010, 53, 2354-2363.

* Malakoutikhah, M. et al. J. Med. Chem. 2008, 51, 4881-4889.

(PhPro)x-CONH2

Small molecules Patent: E. Giralt, M. Teixidó, M. Malakoutikhah

Compounds that act as a vehicle for delivery through the

blood-brain barrier and charge delivery vehicle constructions.

PCT/ES2010/00930.

Publication: Arranz-Gibert, P. et al. JACS, 2015

137, 7357-7364.

Publication: Delivery of gold nanoparticles to the brain as a

potential tool for the treatment of neurodegenerative diseases.

Prades, R.; Guerrero, S.; Araya, E.; Molina, C.; Salas, E.; Zurita,

E.; Selva, J.; Egea, G.; López-Iglesias, C.; Teixidó, M.; Kogan,

M.J.; Giralt, E. Biomaterials, 2012, 33, 7194-7205.

Drug THRPPMWSPVWP

Patent: E. Giralt, M. Teixidó, R. Prades. Protease-resistant

compouds useful as shuttles through the blood-brain barrier and

shuttle-cargo constructs. WO2013/127829 A1.

Publication: Prades, R.; Oller-Salvia, B.; Schwarzmaier, S. M.;

Selva, J.; Moros, M.; Balbi, M.; Grazu, V.; de La Fuente, J. M.;

Egea, G.; Plesnila, N.; Teixidó, M.; Giralt, E. Angew. Chem. Int.

Ed. 2015, 54, 3967-3972.

Half-life

> 24 h

> 24 h

8 min

3 h

> 24 h

MiniAp-4

• Patent: E. Giralt, M. Teixidó, B. Oller,

PCT/EP2014/064173

• Publications:

* Oller-Salvia, B.; Teixidó, M.; Giralt, E.

Biopolymers-Peptide Science, 2013, 100,

675-686.

* Oller-Salvia, B. et al. Angew. Chem.

Int. Ed. 2015, 55, 572-575.

Drug