UV Absorption Spectroscopic Analysis of the Molecular Orientation of a Drug Penetrated into a DPPC Membrane

Abstract

The present study quantitatively measured, via UV absorption spectroscopy, the molecular orientation of the drug chlorpromazine (CPZ) after spontaneous penetration into the gel phase of a phospholipid membrane. An l-α-dipalmitoylphosphatidylcholine (DPPC) Langmuir (L) film (a monolayer on an aqueous solution) was doped with CPZ and transferred onto a quartz substrate to form a Langmuir−Blodgett (LB) film. The transmission spectrum of the LB film was measured using a normal incident, nonpolarized UV beam. To calculate the theoretical absorbances, the extinction coefficients of oriented CPZ molecules in the DPPC LB film were deduced from the molar extinction coefficients of nonoriented, dispersed CPZ molecules in an aqueous solution. The anisotropic extinction coefficient of CPZ was determined with the uniaxial refractive index ellipsoid model as a function of orientation angle, using the extinction coefficient of CPZ in the bulk state. By comparing the theoretical absorbances with observed absorbances, the orientation angles from the surface normal of the LB film of transition moments along the molecular short and long axes were determined to be 17° and 85°, respectively. The results of the present study indicate that CPZ molecules penetrate deep into the DPPC membranes and that the molecular orientation of CPZ is determined by the surrounding DPPC molecules.