EMAIL THIS PAGE TO A FRIEND

Biomaterials

Functionalized nanocarrier combined seizure-specific vector with P-glycoprotein modulation property for antiepileptic drug delivery.


PMID 26447556

Abstract

Despite optimal therapeutic regimen with currently available antiepileptic drugs (AEDs), approximately a third of epilepsy patients remain drug refractory. Region-specific overexpression of multidrug efflux transporters at the blood-brain barrier, such as P-glycoprotein (P-gp), might contribute to multidrug resistance (MDR) by reducing target concentrations of AEDs. Therefore, development of nanomedicine that can modulate P-gp function as well as facilitate targeted AEDs delivery represents a promising strategy for epilepsy intervention. To achieve this, we sought to exploit the possibility of combination of active targeting function of tryptophan by transporter-mediated endocytosis and overcoming MDR by Pluronic block copolymers. Herein, a tryptophan derivate (TD) functionalized Pluronic P123/F127 mixed micelles encapsulating LTG (TD-PF/LTG) was developed to promote AEDs delivery to epileptogenic focus. TD-PF/LTG was about 20 nm in diameter with a spherical shape and high encapsulation efficiency. A rat epilepsy model with pilocarpine was established to evaluate the brain penetration efficiency of the LTG-incorporated polymeric micellar formulation, compared with free LTG formulations. Studies showed that TD-PF/LTG was more efficient than PF/LTG as well as free LTG in delivering the drug to the brain, especially the hippocampus. The enhanced targeted delivery could be ascribed to the increased tryptophan uptake at epileptogenic focus as well as P-gp modulation property of the nanomaterial. Taken together, TD-conjugated Pluronic micelles showed promising potential as a nanoplatform for the delivery of AEDs in refractory epilepsy.

Related Materials

Product #

Image

Description

Molecular Formula

Add to Cart

377848
(Benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate, 98%
C18H28F6N6OP2
A1542
Ammonium acetate, for molecular biology, ≥98%
C2H7NO2
A7330
Ammonium acetate, BioXtra, ≥98%
C2H7NO2
372331
Ammonium acetate, 99.999% trace metals basis
C2H7NO2
431311
Ammonium acetate, ≥99.99% trace metals basis
C2H7NO2
238074
Ammonium acetate, ACS reagent, ≥97%
C2H7NO2
A7262
Ammonium acetate, reagent grade, ≥98%
C2H7NO2
A2706
Ammonium acetate solution, for molecular biology, 7.5 M
C2H7NO2
296082
Diethyl ether, contains 1 ppm BHT as inhibitor, anhydrous, ≥99.7%
C4H10O
09-1833
Diethyl ether, for residue analysis, JIS 5000
C4H10O
09-1855
Diethyl ether
C4H10O
G5417
Glycine, PharmaGrade, Ajinomoto, EP, JP, USP, manufactured under appropriate GMP controls for Pharma or Biopharmaceutical production, suitable for cell culture
C2H5NO2
410225
Glycine, ACS reagent, ≥98.5%
C2H5NO2
G7126
Glycine, ReagentPlus®, ≥99% (HPLC)
C2H5NO2
50046
Glycine, BioUltra, for molecular biology, ≥99.0% (NT)
C2H5NO2
G8898
Glycine, for electrophoresis, ≥99%
C2H5NO2
G7403
Glycine, BioXtra, ≥99% (titration)
C2H5NO2
G8790
Glycine, from non-animal source, meets EP, JP, USP testing specifications, suitable for cell culture, ≥98.5%
C2H5NO2
W328707
Glycine, 99%, FCC
C2H5NO2
T0254
L-Tryptophan, reagent grade, ≥98% (HPLC)
C11H12N2O2
T8941
L-Tryptophan, from non-animal source, meets EP, JP, USP testing specifications, suitable for cell culture, 99.0-101.0%
C11H12N2O2
T4196
L-Tryptophan, PharmaGrade, Ajinomoto, EP, JP, USP, Manufactured under appropriate GMP controls for pharma or biopharmaceutical production, suitable for cell culture
C11H12N2O2
93659
L-Tryptophan, BioUltra, ≥99.5% (NT)
C11H12N2O2
364517
L-Tryptophan methyl ester hydrochloride, 98%
C12H14N2O2 · HCl
L3791
Lamotrigine, ≥98%, powder
C9H7Cl2N5
746460
Lithium chloride, anhydrous, free-flowing, Redi-Dri, ACS reagent, ≥99%
ClLi
793620
Lithium chloride, anhydrous, free-flowing, Redi-Dri, ReagentPlus®, 99%
ClLi
L4408
Lithium chloride, BioXtra, ≥99.0% (titration)
ClLi
62476
Lithium chloride, BioUltra, for molecular biology, anhydrous, ≥99.0% (AT)
ClLi
L9650
Lithium chloride, for molecular biology, ≥99%
ClLi