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AAPS PharmSciTech

, 20:317 | Cite as

Selectivity Enhancement of Paclitaxel Liposome Towards Folate Receptor-Positive Tumor Cells by Ligand Number Optimization Approach

  • Mahendra Kumar Prajapati
  • Aniketh Bishnu
  • Pritha Ray
  • Pradeep R. VaviaEmail author
Research Article
  • 27 Downloads

Abstract

The present work aims to develop folate-targeted paclitaxel liposome (F-PTX-LIP), which will selectively target tumor cells overexpressing folate receptor (FR) and leave normal cells. Liposomes were prepared by thin-film hydration method followed by post-insertion of synthesized ligand 1,2-distearoyl-sn-glycero-phosphoethanolamine-polyethyleneglycol 2000-folic acid (DSPE-PEG2000-FA) on the outer surface of the liposome. The synthesized ligand was evaluated for in vivo acute toxicity in Balb/c mice. Developed liposomal formulations were characterized using transmission electron microscopy (TEM) and small-angle neutron scattering (SANS). We have investigated the effect of ligand number on cell uptake and cytotoxicity by confocal laser scanning microscopy (CLSM), competitive inhibition and 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assay. Compared to lung adenocarcinoma cells (A549), uptake in human ovarian carcinoma cells (SKOV3) was 2.2- and 1.2-fold higher for liposome with 480 and 240 ligand number respectively. Competitive inhibition experiment shows that prior incubation of SKOV3 cells with free folic acid significantly reduced the cell uptake of F-PTX-LIP with 480 ligand number (480 F-PTX-LIP) by 2.6-fold. 480 F-PTX-LIP displays higher cytotoxicity than free drug and PTX liposome. Moreover, it specifically targets the cells with higher folate receptor expression. Optimized 480 F-PTX-LIP formulation can be potentially useful for the treatment of folate receptor-positive tumors.

KEY WORDS

nanotechnology liposome paclitaxel DSPE-PEG2000-Folate ligand number folate receptor targeting 

Abbreviations

FR

folate receptor

PTX

paclitaxel

PTX-LIP

paclitaxel liposome

F-PTX-LIP

folate-targeted paclitaxel liposome

DSPE-PEG2000

1,2-distearoyl-sn-glycero-3-phosphoethanolamine-polyethyleneglycol 2000

DSPE-PEG 2000-FA

1,2-distearoyl-sn-glycero-3-phosphoethanolamine-polyethyleneglycol 2000-folic acid

PS

particle size

PDI

polydispersity index

ZP

zeta potential

% EE

percent drug entrapment efficiency

% DL

percent drug loading

TEM

transmission electron microscopy

SANS

small-angle neutron scattering

DSC

differential scanning calorimetry

CLSM

confocal laser scanning microscopy

MTT

3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

F-LIP

FR-targeted liposomes

NF-LIP

folate receptor-targeted liposomes with no ligand

b-LIP

blank liposome

240 F-LIP

folate receptor-targeted liposomes with 240 ligand per liposome

480 F-LIP

folate receptor-targeted liposomes with 480 ligand per liposome

240 F-PTX-LIP

folate receptor-targeted paclitaxel liposomes with 240 ligand per liposome

480 F-PTX-LIP

folate receptor-targeted paclitaxel liposomes with 480 ligand per liposome

PEG

polyethylene glycols

SPC

soya phosphatidylcholine LIPOID S100

DCP

dihexadecylphosphate

DCC

dicyclohexylcarbodiimide

NHS

N-hydroxysuccinimide

TEA

triethylamine

DLS

dynamic light scattering

FTIR

Fourier transform infrared

PSD

position-sensitive detector

RPMI

Roswell Park Memorial Institute

1H NMR

proton nuclear magnetic resonance

MFI

mean fluorescence intensity

Notes

Acknowledgments

The authors would like to acknowledge the Council of Scientific and Industrial Research (CSIR), New Delhi, and Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Mumbai, for providing fellowship. They are also thankful to AICTE-NAFETIC for providing research facilities.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

12249_2019_1531_MOESM1_ESM.docx (767 kb)
ESM 1 (DOCX 767 kb)

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Copyright information

© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  • Mahendra Kumar Prajapati
    • 1
  • Aniketh Bishnu
    • 2
  • Pritha Ray
    • 2
  • Pradeep R. Vavia
    • 1
    Email author
  1. 1.Center for Novel Drug Delivery Systems, Department of Pharmaceutical Sciences and Technology, Institute of Chemical TechnologyUniversity Under Section 3 of UGC Act – 1956, Elite Status and Center of Excellence – Govt. of Maharashtra, TEQIP Phase III FundedMumbaiIndia
  2. 2.Advance Centre for Treatment, Research and Education in Cancer, Tata Memorial CentreKhargharIndia

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