Spray-dried microparticles containing polymeric micelles encapsulating hematoporphyrin

The purpose of this study was to examine the properties of a new pulmonary delivery platform of microparticles containing micelles in which a therapeutic photosensitizing drug, hematoporphyrin (Hp), was encapsulated. Different poloxamers were used to form micellar Hp, and one of these, Pluronic L122-Hp, was subsequently incorporated into lactose microparticles by spray-drying. Spectral and morphological analyses were performed on both micellar Hp, and lactose microparticles containing micellar Hp (lactose-micellar Hp) before and after dissolution of the microparticles in water. Photodynamic activity of the various Hp samples were evaluated in human lung epithelial carcinoma A549 cells using a light-emitting diode (LED) device at a wavelength of 630 +/- 5 nm. No significant difference was observed between micellar Hp and lactose-micellar Hp regarding the generation of singlet oxygen. The mean particle size of the microparticles was 2.3 +/- 0.7 microm which is within the size range for potential lung delivery. The cellular uptake of micellar Hp and lactose-micellar Hp measured on A549 cells was at least twofold higher than those obtained with the Hp at equivalent concentrations. Micellar Hp exhibited higher cytotoxicity than Hp due to reduced formation of Hp aggregates and increased cellar uptake. The spectral properties as well as the photodynamic activity of the micellar Hp was retained when formulated into microparticles by spray-drying. Microparticles containing micelles have the potential for delivering micelle-encapsulated hydrophobic drugs in targeted therapy of pulmonary diseases.