UV ABSORPTION SPECTROSCOPIC ANALYSIS OF THE MOLECULAR-ORIENTATION OF A DRUG PENETRATED INTO A DPPC MEMBRANE

The present study quantitatively measured, via UV absorption spectrosc opy, the molecular orientation of the drug chlorpromazine (CPZ) after spontaneous penetration into the gel phase of a phospholipid membrane. An L-alpha-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 tra nsmission 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, di spersed CPZ molecules in an aqueous solution. The anisotropic extincti on coefficient of CPZ was determined with the uniaxial refractive inde x ellipsoid model as a function of orientation angle, using the extinc tion coefficient of CPZ in the bulk state. By comparing the theoretica l absorbances with observed absorbances, the orientation angles from t he surface normal of the LB film of transition moments along the molec ular short and long axes were determined to be 17 degrees and 85 degre es, respectively. The results of the present study indicate that CPZ m olecules penetrate deep into the DPPC membranes and that the molecular orientation of CPZ is determined by the surrounding DPPC molecules.