Brain-targeted delivery of trans-activating transcriptor-conjugated magnetic PLGA/lipid nanoparticles

Xiangru Wen; Kai Wang; Ziming Zhao; Yifang Zhang; Tingting Sun; Fang Zhang; Jian Wu; Yanyan Fu; Yang Du; Lei Zhang; Ying Sun; YongHai Liu; Kai Ma; Hongzhi Liu; Yuanjian Song

doi:10.1371/journal.pone.0106652

Brain-targeted delivery of trans-activating transcriptor-conjugated magnetic PLGA/lipid nanoparticles

PLoS One. 2014 Sep 4;9(9):e106652. doi: 10.1371/journal.pone.0106652. eCollection 2014.

Authors

Xiangru Wen¹, Kai Wang², Ziming Zhao³, Yifang Zhang², Tingting Sun², Fang Zhang⁴, Jian Wu⁴, Yanyan Fu⁴, Yang Du⁴, Lei Zhang⁵, Ying Sun⁵, YongHai Liu⁵, Kai Ma⁶, Hongzhi Liu⁴, Yuanjian Song⁷

Affiliations

¹ Jiangsu Key Laboratory of Brain Disease Bioinformation, Xuzhou Medical College, Xuzhou, Jiangsu Province, China; School of Basic Education Sciences, Xuzhou Medical College, Xuzhou, Jiangsu Province, China.
² College of Animal Science and Technology, Yunnan Agricultural University, Yunnan, Kunming Province, China.
³ School of Pharmacy, Xuzhou Medical College, Xuzhou, Jiangsu Province, China.
⁴ Research Center for Neurobiology and Department of Neurobiology, Xuzhou Medical College, Xuzhou, Jiangsu Province, China.
⁵ Department of Neurology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu Province, China.
⁶ School of Basic Education Sciences, Xuzhou Medical College, Xuzhou, Jiangsu Province, China; Department of Medical Information, Xuzhou Medical College, Xuzhou, Jiangsu Province, China.
⁷ Jiangsu Key Laboratory of Brain Disease Bioinformation, Xuzhou Medical College, Xuzhou, Jiangsu Province, China; Research Center for Neurobiology and Department of Neurobiology, Xuzhou Medical College, Xuzhou, Jiangsu Province, China.

Abstract

Magnetic poly (D,L-lactide-co-glycolide) (PLGA)/lipid nanoparticles (MPLs) were fabricated from PLGA, L-α-phosphatidylethanolamine (DOPE), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-amino (polyethylene glycol) (DSPE-PEG-NH2), and magnetic nanoparticles (NPs), and then conjugated to trans-activating transcriptor (TAT) peptide. The TAT-MPLs were designed to target the brain by magnetic guidance and TAT conjugation. The drugs hesperidin (HES), naringin (NAR), and glutathione (GSH) were encapsulated in MPLs with drug loading capacity (>10%) and drug encapsulation efficiency (>90%). The therapeutic efficacy of the drug-loaded TAT-MPLs in bEnd.3 cells was compared with that of drug-loaded MPLs. The cells accumulated higher levels of TAT-MPLs than MPLs. In addition, the accumulation of QD-loaded fluorescein isothiocyanate (FITC)-labeled TAT-MPLs in bEnd.3 cells was dose and time dependent. Our results show that TAT-conjugated MPLs may function as an effective drug delivery system that crosses the blood brain barrier to the brain.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Brain / metabolism*
Drug Delivery Systems / methods
Flavanones / chemistry
Glutathione / chemistry
Hesperidin / chemistry
Humans
Lactic Acid / chemistry*
Nanoparticles / chemistry*
Phosphatidylethanolamines / chemistry
Polyethylene Glycols / chemistry
Polyglycolic Acid / chemistry*
Polylactic Acid-Polyglycolic Acid Copolymer

Substances

Flavanones
Phosphatidylethanolamines
polyethylene glycol-distearoylphosphatidylethanolamine
Polylactic Acid-Polyglycolic Acid Copolymer
Polyglycolic Acid
Lactic Acid
Polyethylene Glycols
Hesperidin
Glutathione
naringin

Grants and funding

This work was supported by Jiangsu Key Laboratory of Brain Disease Bioinformation (Jsbl1102), the Priority Academic Program Development of Jiangsu Higher Education Institutions, the Education Departmental Natural Science Research Funds of Jiangsu Provincial Higher School of China (13KJB310021), the National Natural Science Foundation of China (31100762, 81371300), the Foundation of President of Xuzhou Medical College (2012KJZ06), and the Qing Lan Project of Jiangsu Province. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.