THE INFLUENCE OF CHLORPROMAZINE HYDROCHLORIDE ON THE THERMOTROPIC BEHAVIOR OF DIMYRISTOYL PHOSPHATIDYLCHOLINE LIPOSOMES AS REVEALED BY DIFFERENTIAL SCANNING CALORIMETRY

FARAH HAMAD FARAH

doi:10.22159/ijap.2022v14i3.42870

Authors

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 https://orcid.org/0000-0003-3339-9743

DOI:

https://doi.org/10.22159/ijap.2022v14i3.42870

Keywords:

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

Abstract

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-T_C) 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 ΔH_t, ΔS_t, Tc, pre-Tc and HHW of DSC thermograms of DMPC liposomes. The effect of sonication on ΔH_t, ΔS_t, 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 ΔH_t, ΔS_t and Tc of DMPC/CPZ-HCl liposomes. In addition, the effect of CPZ-HCl at concentrations known to cause anesthesia on ΔH_t, ΔS_t. 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 ΔH_t, ΔS_t, T_C, the pre-T_C and increases HHW of DMPC liposomes. ΔH_t and ΔS_t 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 ΔH_t and ΔS_t 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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