title: Targeting delivery of etoposide to inhibit the growth of human glioblastoma multiforme using lactoferrin- and folic acid-grafted poly(lactide-co-glycolide) nanoparticles.
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.
authors.affiliation: Department of Chemical Engineering, National Chung Cheng University, Chia-Yi, Taiwan 62102. Electronic address: chmyck@ccu.edu.tw.
authors.forename: Yung-Chih
authors.initials: YC
authors.lastname: Kuo
authors.affiliation: Department of Chemical Engineering, National Chung Cheng University, Chia-Yi, Taiwan 62102.
authors.forename: Yu-Chun
authors.initials: YC
authors.lastname: Chen
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000737:chemistry; D001253:Astrocytes; D001812:Blood-Brain Barrier / Q000378:metabolism; D001932:Brain Neoplasms; D045744:Cell Line, Tumor; D002470:Cell Survival; D002478:Cells, Cultured; D016503:Drug Delivery Systems; D042783:Endothelial Cells; D005047:Etoposide / Q000008:administration & dosage* / Q000737:chemistry; D058973:Folate Receptors, GPI-Anchored / Q000378:metabolism; D005492:Folic Acid / Q000737:chemistry*; D005909:Glioblastoma; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry; D007781:Lactoferrin / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000648:ultrastructure; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011956:Receptors, Cell Surface / Q000378:metabolism; D059005:Topoisomerase II Inhibitors / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D058973:Folate Receptors, GPI-Anchored; D011956:Receptors, Cell Surface; D059005:Topoisomerase II Inhibitors; C038340:lactoferrin receptors; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D005047:Etoposide; D005492:Folic Acid; D007781:Lactoferrin
keywords: Blood–brain barrier; Etoposide; Folic acid; Glioblastoma multiforme; Lactoferrin; Poly(lactide-co-glycolide)