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Research ArticleExperimental Studies

Synthesis and Evaluation of a Hematoporphyrin Derivative in a Folate Receptor-targeted Solid-Lipid Nanoparticle Formulation

PHILLIP J. STEVENS, MASARU SEKIDO and ROBERT J. LEE
Anticancer Research January 2004, 24 (1) 161-166;
PHILLIP J. STEVENS
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MASARU SEKIDO
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ROBERT J. LEE
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Abstract

Purpose: This study was aimed at the synthesis, formulation and in vitro evaluation of folate receptor (FR)- targeted solid-lipid nanoparticles (SLNs) as a carrier for a lipophilic derivative of the photosensitizer hematoporphyrin (Hp), in FR-overexpressing tumor cells. Materials and Methods: FR-targeted hematoporphyrin-stearylamine (HpSa) SLN composed of Triolein:Egg-phosphatidylcholine (EPC):Tween-80 (T-80) (64:25:10), with 0.5 mole % of folatepolyethyleneglycol- cholesterol (FPC) or polyethyleneglycoldistearoylphosphatidylethanolamine (PEG-DSPE), were prepared by ethanol injection method. Stability of the SLN was monitored by changes in particle size at 4°C and drug retention at various time points. Cellular uptake and IC50 values of the FR-targeted formulations were determined in vitro in the FR (+) KB cells. Results: Stable targeted SLNs were prepared by ethanol injection encapsulating greater than 95 percent of 5 mole % of HpSa, having a mean diameter < 200 nm. In vitro cytotoxicity assay on the FR-targeted SLN gave IC50 of 1.57 μM in KB cells and non-targeted SLNs gave an IC50 of 5.17 μM. FR selectivity was confirmed by fluorescence microscopy. Conclusion: FR-targeted SLNs incorporating the lipophilic drug HpSa were capable of specific receptor binding in cultured KB cells, which warrants further investigation.

  • Received November 19, 2003.
  • Accepted December 23, 2003.
  • Copyright© 2004 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved
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Anticancer Research: 24 (1)
Anticancer Research
Vol. 24, Issue 1
January-February 2004
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Synthesis and Evaluation of a Hematoporphyrin Derivative in a Folate Receptor-targeted Solid-Lipid Nanoparticle Formulation
PHILLIP J. STEVENS, MASARU SEKIDO, ROBERT J. LEE
Anticancer Research Jan 2004, 24 (1) 161-166;

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Synthesis and Evaluation of a Hematoporphyrin Derivative in a Folate Receptor-targeted Solid-Lipid Nanoparticle Formulation
PHILLIP J. STEVENS, MASARU SEKIDO, ROBERT J. LEE
Anticancer Research Jan 2004, 24 (1) 161-166;
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