Objective   It was demonstrated from our previous studies that chlorpromazine hydrochloride can increase the relative bioavailabilities of drugs through rectal administration

due to the alternations of cell membrane architecture and permeability caused by the amphipathic structure of chlorpromazine hydrochloride. To prove this mechanism

Caco-2 cell membrane was exploited to investigate the effect of chlorpromazine hydrochloride on the membrance’s integrities and stabilities.    Methods   After the Caco-2 cells were treated with chlorpromazine hydrochloride at different concentrations for different durations

the optical density value (OD-value) of the supernatant was determined by Bradford protein assays. The calculated OD ratios showed the changes of Caco-2 cell membrane integrity. The fluorescent intensity (fluorescence polarization

Pr) was determined by fluorescence spectrophotometer with 1

6-diphenyl-1

3

5-hexatriene (DPH) as a fluorescein probe

the mobility and stability of Caco-2 cell membrane were evaluated by the calculated Pr’s data.    Results   Compared with the control

Caco-2 cell membrane was damaged at different degrees by high-dose chlorpromazine hydrochloride (140 μmol/L)

and the intracellular content was poured out. It was observed an S-shape curve between the membrane-damaged percentage vs the concentrations of chlorpromazine hydrochloride. Meanwhile

degression of the fluorescence polarization (Pr) of Caco-2 cell membrane was observed after the Caco-2 cells treated with low-dose chlorpromazine hydrochloride

and Pr values were decreased with the increase of concentration of chlorpromazine hydrochloride and extension of treatment time (P0.05). A significant negative correlation was found between Pr value and duration at the same concentration group (P0.05).    Conclusion   Low dose chlorpromazine hydrochloride increases lipid fluidity and changes the stability of Caco-2 cell membrane

and even damages cell membrane integrity when the concentration is increased or treatment time prolonged

resulting in the increase of cell membrane permeability. The changes of cell membrane may be one of mechanisms for promoting the rectal absorption of drugs by chlorpromazine hydrochloride.