Neuroprotective peptide drug delivery and development: potential new therapeutics

Gozes, Illana

doi:10.1016/s0166-2236(00)01931-7

Cited by 71 publications

(34 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This strategy had physiological consequences, because intracarotid artery perfusion of biotinylated VIP coupled to OX26/avidin resulted in an increased brain blood flow (Wu and Pardridge, 1996). Alternative routes of administration also include intranasal drug delivery, which circumvents the brain-blood barrier and has been demonstrated to be effective for other peptides (reviewed by Gozes, 2001). …”

Section: Effects Of Vasoactive Intestinal Peptide In Brain Inflammentioning

confidence: 99%

The Significance of Vasoactive Intestinal Peptide in Immunomodulation

Delgado

Pozo²,

Ganea³

2004

Pharmacological Reviews

372

319

View full text Add to dashboard Cite

Section: Effects Of Vasoactive Intestinal Peptide In Brain Inflammentioning

confidence: 99%

The Significance of Vasoactive Intestinal Peptide in Immunomodulation

Delgado

Pozo²,

Ganea³

2004

Pharmacological Reviews

372

319

View full text Add to dashboard Cite

“…All transport experiments were conducted in triplicate. Apparent permeability coefficients (P app ) of the polypletides were calculated using the following equation: (2) where dQ/dt is the flux across the cell monolayers, A is the surface area of the membrane, and C 0 is the initial concentration of the drug.…”

Section: Transport Of Hrp Conjugates Across Bbmec Monolayersmentioning

confidence: 99%

Polypeptide Point Modifications with Fatty Acid and Amphiphilic Block Copolymers for Enhanced Brain Delivery

Batrakova

Vinogradov²,

Robinson

et al. 2005

Bioconjugate Chem.

View full text Add to dashboard Cite

There is a tremendous need to enhance delivery of therapeutic polypeptides to the brain to treat disorders of the central nervous system (CNS). The brain delivery of many polypeptides is severely restricted by the blood-brain barrier (BBB). The present study demonstrates that point modifications of a BBB-impermeable polypeptide, horseradish peroxidase (HRP), with lipophilic (stearoyl) or amphiphilic (Pluronic block copolymer) moieties considerably enhance the transport of this polypeptide across the BBB and accumulation of the polypeptide in the brain in vitro and in vivo. The enzymatic activity of the HRP was preserved after the transport. The modifications of the HRP with amphiphilic block copolymer moieties through degradable disulfide links resulted in the most effective transport of the HRP across in vitro brain microvessel endothelial cell monolayers and efficient delivery of HRP to the brain. Stearoyl modification of HRP improved its penetration by about 60% but also increased the clearance from blood. Pluronic modification using increased penetration of the BBB and had no significant effect on clearance so that uptake by brain was almost doubled. These results show that point modification can improve delivery of even highly impermeable polypeptides to the brain.

show abstract

“…These effects of VIP are enable through the VPAC1 receptor. VIP binding to VPAC1 sets off a cascade of reactions involving the cAMP/PKA pathway which in sequence activates neurotrophic dependent factors to enhance neuroinal survival (Gozes, 2001). VIP also inhibits IKK, p38 and p42 responsible for NFκB activation and proinflammaotry cytokine release (Delgado et al, 2008b).…”

Section: Alzheimer Diseasementioning

confidence: 99%