Effects of Particle Size and Cholesterol Content on the Partition Coefficients of Chlorpromazine and Triflupromazine between Phosphatidylcholine–Cholesterol Bilayers of Unilamellar Vesicles and Water Studied by Second-Derivative Spectrophotometry
✍ Scribed by Shigehiko Takegami; Keisuke Kitamura; Tatsuya Kitade; Kazuhiro Hasegawa; Aya Nishihira
- Publisher
- Elsevier Science
- Year
- 1999
- Tongue
- English
- Weight
- 115 KB
- Volume
- 220
- Category
- Article
- ISSN
- 0021-9797
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✦ Synopsis
Phosphatidylcholine (PC)-cholesterol (0 -30 mol%) unilamellar vesicles of several sizes (20 -600 nm) were prepared in buffer (pH 7.4) solutions by sonication or extrusion methods. The vesicle size was measured by a dynamic light-scattering method. Absorption spectra of chlorpromazine (CPZ) and triflupromazine (TFZ) in the presence of these vesicles showed a bathochromic shift according to the increase in vesicle concentration, but the counterbalance of the baseline was incomplete due to the intensive light scattering by the vesicles; thus, no isosbestic point could be observed. In the second-derivative spectra, the residual background signal effects were eliminated and three derivative isosbestic points were clearly observed for both drugs. The derivative intensity change (⌬D) induced by the addition of the vesicles was measured at the max of each drug. From the relationship between the ⌬D value and the lipid concentration, the partition coefficients (K p ) of CPZ and TFZ between these vesicles and water (buffer) were calculated. The results revealed that the vesicle size (20 -600 nm) and preparation method do not affect the K p values, and although the incorporation of cholesterol into the PC bilayers induces a decrease of the K p values, the vesicle size also did not affect the K p values in vesicles of the same cholesterol content.