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


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.


CONCLUSIONS
FR-targeted SLNs incorporating the lipophilic drug HpSa were capable of specific receptor binding in cultured KB cells, which warrants further investigation.
Stevens
Phillip J
PJ
Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, Ohio 43210, USA.
Sekido
Masaru
M
Lee
Robert J
RJ
D000588:Amines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D002352:Carrier Proteins / Q000378:metabolism*; D004354:Drug Screening Assays, Antitumor; D058973:Folate Receptors, GPI-Anchored; D006415:Hematoporphyrins / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D007624:KB Cells; D008055:Lipids / Q000737:chemistry / Q000493:pharmacokinetics; D008081:Liposomes; D008856:Microscopy, Fluorescence; D036103:Nanotechnology; D010316:Particle Size; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D011956:Receptors, Cell Surface
D000588:Amines; D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D006415:Hematoporphyrins; D008055:Lipids; D008081:Liposomes; D017319:Photosensitizing Agents; D011956:Receptors, Cell Surface; C009317:stearylamine