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

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.