Targeting delivery of etoposide to inhibit the growth of human glioblastoma multiforme using lactoferrin- and folic acid-grafted poly(lactide-co-glycolide) nanoparticles.

Targeting delivery of etoposide to inhibit the growth of human glioblastoma multiforme using lactoferrin- and folic acid-grafted poly(lactide-co-glycolide) nanoparticles.

International journal of pharmaceutics (2015-01-07)

Yung-Chih Kuo, Yu-Chun Chen

ABSTRACT

Lactoferrin (Lf) and folic acid (FA) were crosslinked on poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) for transporting etoposide across the blood-brain barrier (BBB) and treating human brain malignant glioblastoma. Lf- and FA-grafted PLGA NPs (Lf/FA/PLGA NPs) were employed to permeate the monolayer of human brain-microvascular endothelial cells (HBMECs) regulated by human astrocytes and to inhibit the multiplication of U87MG cells. Lf/FA/PLGA NPs showed a satisfactory entrapment efficiency of etoposide and characteristics of sustained drug release. When compared with PLGA NPs, the permeability coefficient for etoposide across the BBB using Lf/FA/PLGA NPs increased about twofold. The antiproliferative efficacy against the growth of U87MG cells was in the following order: Lf/FA/PLGA NPs>FA/PLGA NPs>PLGA NPs>free etoposide solution. In addition, the targeting ability of Lf/FA/PLGA NPs was evidenced by immunostaining of Lf receptor on HBMECs and folate receptor on U87MG cells during endocytosis. Lf/FA/PLGA NPs with loaded etoposide can be a promising anticancer pharmacotherapy to enhance the delivery of etoposide to malignant brain tumors for preclinical trials.

MATERIALS

Product Number

Brand

Product Description

93350

Sigma-Aldrich

Trizma^® base, puriss. p.a., ≥99.7% (T)

93440

Supelco

Trizma^® base, reference material for titrimetry, certified by BAM, >99.5%

34613

Millipore

Acetonitrile solution, suitable for HPLC, acetonitrile:water 5:95% (v/v), 10 mM Ammoniumbicarbonate, pH 10,0

02560

Supelco

4-(Dimethylamino)benzaldehyde solution, 10 g/L in isopropanol, for TLC derivatization

T6066

Sigma-Aldrich

Trizma^® base, BioPerformance Certified, meets EP, USP testing specifications, suitable for cell culture, ≥99.9% (titration)

S8032

Sigma-Aldrich

Sodium azide, BioXtra

F7250

Sigma-Aldrich

Fluorescein isothiocyanate isomer I, suitable for protein labeling, ≥90% (HPLC), powder

F4274

Sigma-Aldrich

Fluorescein isothiocyanate isomer I, ≥97.5% (HPLC)

D2004

Sigma-Aldrich

4-(Dimethylamino)benzaldehyde, suitable for histochemical demonstration of nitro blue tetrazolium reduction in neutrophils

T6687

Sigma-Aldrich

Tromethamine, meets USP testing specifications

71289

Sigma-Aldrich

Sodium azide, BioUltra, ≥99.5% (T)

156477

Sigma-Aldrich

4-(Dimethylamino)benzaldehyde, ACS reagent, 99%

93362

Sigma-Aldrich

Trizma^® base, BioUltra, for molecular biology, ≥99.8% (T)

93352

Sigma-Aldrich

Trizma^® base, ≥99.0% (T)

71631

Sigma-Aldrich

Sodium bicarbonate, tested according to Ph. Eur.

33130

Sigma-Aldrich

4-(Dimethylamino)benzaldehyde, puriss. p.a., reag. Ph. Eur., ≥99% (perchloric acid titration)

359025

Sigma-Aldrich

Didodecyldimethylammonium bromide, 98%

469548

Sigma-Aldrich

1,1,1-Trifluoro-5,5-dimethyl-2,4-hexanedione, 98%

252859

Sigma-Aldrich

Tris(hydroxymethyl)aminomethane, ACS reagent, ≥99.8%

109762

Sigma-Aldrich

4-(Dimethylamino)benzaldehyde, 98%

T1503

Sigma-Aldrich

Trizma^® base, Primary Standard and Buffer, ≥99.9% (titration), crystalline

S2002

Sigma-Aldrich

Sodium azide, ReagentPlus^®, ≥99.5%

T4661

Sigma-Aldrich

Trizma^® base, ≥99.9% (titration), crystalline

S5761

Sigma-Aldrich

Sodium bicarbonate, powder, BioReagent, for molecular biology, suitable for cell culture, suitable for insect cell culture

S6297

Sigma-Aldrich

Sodium bicarbonate, BioXtra, 99.5-100.5%

T6791

Sigma-Aldrich

Trizma^® base, BioXtra, pH 10.5-12.0 (1 M in H₂O), ≥99.9% (titration)

71290

Sigma-Aldrich

Sodium azide, purum p.a., ≥99.0% (T)

1613655

USP

Sodium bicarbonate, United States Pharmacopeia (USP) Reference Standard

13433

Sigma-Aldrich

Sodium bicarbonate, puriss., meets analytical specification of Ph. Eur., BP, USP, FCC, E500, 99.0-100.5%, powder

900506

Sigma-Aldrich

Sodium bicarbonate, anhydrous, free-flowing, Redi-Dri^™, ReagentPlus^®, ≥99.5%