• FARAH HAMAD FARAH Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, India, Center of Medical and Bio-allied Health Sciences Research, Ajman University, Ajman, United Arab Emirates



CPZ-HCl, Liposomes, Transition temperature, Enthalpy, Entropy


Objective: The aim of this study is to investigate the influence of the model cationic, amphiphilic, drug chlorpromazine hydrochloride (CPZ-HCl) on the thermotropic behavior of dimyristoyl phosphatidylcholine (DMPC) liposomes, using differential scanning calorimetry (DSC). The effect of sonication, charged lipids and CPZ-HCl at concentrations known to cause anesthesia on the enthalpy (ΔHt), entropy (ΔSt), phase transition (Tc), pre-transition (pre-TC) and half-height width (HHW) of DSC thermograms were examined.

Methods: The experiments conducted, using the Perkin Elmer (DSC-2C), include the effect of a wide range of CPZ-HCl concentrations on ΔHt, ΔSt, Tc, pre-Tc and HHW of DSC thermograms of DMPC liposomes. The effect of sonication on ΔHt, ΔSt, Tc and HHW of DSC thermograms of DMPC/CPZ-HCl liposomes as a function of sonication time. The effect of both positively charged stearyl amine (ST) and negatively charged diacetyl phosphate (DCP) lipids on ΔHt, ΔSt and Tc of DMPC/CPZ-HCl liposomes. In addition, the effect of CPZ-HCl at concentrations known to cause anesthesia on ΔHt, ΔSt. and Tc of DMPC liposomes in the presence and absence of ST and DCP in phosphate buffer (pH 7.4), was also carried out.

Results: Using DSC, CPZ-HCl concentrations as low as 1×10-7M were observed to alter the gel-liquid crystalline phase transition and thus to possess a membrane destabilizing effect. CPZ-HCl reduces ΔHt, ΔSt, TC, the pre-TC and increases HHW of DMPC liposomes. ΔHt and ΔSt of DMPC liposomes were observed to decrease with increasing CPZ-HCl concentrations, exhibiting an inflection point at 5×10-5M. ΔHt of DMPC liposomes was observed to decrease linearly in the absence and presence of and CPZ-HCl as a function of sonication time. Both ΔHt and ΔSt of DMPC liposomes were observed to increase in the presence of cationic lipid (ST) and to decrease in the presence of anionic lipid (DCP). ΔSt and Tc of DMPC, DMPC/ST, DMPC/DCP liposomes, were found to decrease as a function of CPZ-HCl concentrations known to cause anesthesia.

Conclusion: Using DSC, CPZ-HCl concentrations, as low as 1×10-7 M were observed to influence the enthalpy, entropy, phase transition, pre-transition and half-height width of DSC thermograms of DMPC liposomes, altering the gel-liquid crystalline phase transition and thus possessing a membrane destabilizing effect. It can also be inferred that CPZ-HCl interacts with both the polar head group and the hydrophobic interior of the phospholipid bilayer. These results could support the hypothesis that the addition of local anesthetics might trigger a change in the lipid surrounding the sodium channel from the gel to the liquid crystalline state, allowing the sodium channel to close with the resulting anesthesia.


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