Inhibition Against Growth of Glioblastoma Multiforme In Vitro Using Etoposide‐Loaded Solid Lipid Nanoparticles with p‐Aminophenyl‐α‐d‐Manno‐Pyranoside and Folic Acid

• Published in: Journal of pharmaceutical sciences Vol. 104; no. 5; pp. 1804 - 1814
• Main Authors: Kuo, Yung‐Chih, Lee, Chia‐Hao
• Format: Journal Article
• Language: English
• Published: United States 01.05.2015
• Subjects: Antineoplastic Agents, Phytogenic - administration & dosage; Antineoplastic Agents, Phytogenic - chemistry; blood–brain barrier; cancer chemotherapy; Cell Survival - drug effects; drug targeting; etoposide; Etoposide - administration & dosage; Etoposide - chemistry; folic acid; Folic Acid - administration & dosage; Folic Acid - chemistry; Glioblastoma - drug therapy; Glioblastoma - pathology; glioblastoma multiforme; Humans; Lipids; Mannose - administration & dosage; Mannose - chemistry; microemulsions; Nanoparticles - administration & dosage; Nanoparticles - chemistry; p‐aminophenyl‐α‐d‐manno‐pyranoside; solid lipid nanoparticle; targeted drug delivery; blood-brain barrier; drug targeting; glioblastoma multiforme; microemulsions; cancer chemotherapy; targeted drug delivery; etoposide; folic acid; p-aminophenyl-α-d-manno-pyranoside; solid lipid nanoparticle
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.24388

Solid lipid nanoparticles (SLNs) grafted with p‐aminophenyl‐α‐d‐manno‐pyranoside (APMP) and folic acid (FA) (APMP–FA–SLNs) were applied to encapsulate 4′‐demethylepipodophyllotoxin 9‐(4,6‐O‐ethylidene‐β‐d‐glucopyranoside) (etoposide) (ETP) for promoting the antiproliferation of malignant glioblastoma multiforme. ETP‐loaded APMP–FA–SLNs (APMP–FA–ETP–SLNs) were used to penetrate the blood–brain barrier (BBB) and retard the propagation of U87MG cells. An incorporation of APMP and FA increased the particle size, the cytotoxicity to U87MG cells, and the permeability coefficient for propidium iodide and ETP across the BBB. In addition, an increase in the APMP and FA concentration reduced the zeta potential, the grafting efficiency of APMP and FA, the dissolution rate of ETP, and the transendothelial electrical resistance. Immunochemical staining images evidenced that APMP–FA–ETP–SLNs could infiltrate the BBB via glucose transporter 1 and recognize U87MG cells via folate receptor. APMP–FA–ETP–SLNs can be an effective pharmacotherapeutic formulation in targeting delivery to the brain and in inhibitory efficacy against tumorous cells for cancer therapy. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:1804–1814, 2015