Synthesis and evaluation of a hematoporphyrin derivative in a folate receptor-targeted solid-lipid nanoparticle formulation

Anticancer Res. 2004 Jan-Feb;24(1):161-5.

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 folate-polyethyleneglycol-cholesterol (FPC) or polyethyleneglycol-distearoylphosphatidylethanolamine (PEG-DSPE), were prepared by ethanol injection method. Stability of the SLN was monitored by changes in particle size at 4 degrees 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 microM in KB cells and non-targeted SLNs gave an IC50 of 5.17 microM. 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amines / chemical synthesis*
  • Amines / pharmacokinetics
  • Amines / pharmacology*
  • Carrier Proteins / metabolism*
  • Drug Screening Assays, Antitumor
  • Folate Receptors, GPI-Anchored
  • Hematoporphyrins / chemical synthesis*
  • Hematoporphyrins / pharmacokinetics
  • Hematoporphyrins / pharmacology*
  • Humans
  • KB Cells
  • Lipids / chemistry
  • Lipids / pharmacokinetics
  • Liposomes
  • Microscopy, Fluorescence
  • Nanotechnology
  • Particle Size
  • Photosensitizing Agents / chemical synthesis
  • Photosensitizing Agents / pharmacokinetics
  • Photosensitizing Agents / pharmacology
  • Receptors, Cell Surface*

Substances

  • Amines
  • Carrier Proteins
  • Folate Receptors, GPI-Anchored
  • Hematoporphyrins
  • Lipids
  • Liposomes
  • Photosensitizing Agents
  • Receptors, Cell Surface
  • stearylamine