A comparative study on the effect of Curcumin and Chlorin-p6 on the transport of the LDS cation across a negatively charged POPG bilayer: Effect of pH.

We report the use of interface selective Second Harmonic generation technique to investigate the transport of the LDS cation across POPG liposomes in the pH range of 4.0 to 8.0 in the presence and absence of two amphiphilic drugs, Curcumin and Chlorin-p6 (Cp6). Our results show that bilayer permeability of liposomes is significantly affected by the presence of the drugs and pH of the medium as evidenced by significant changes in the transport kinetics of the LDS. Studies carried out in the pH range 4.0-8.0 show that while Cp6 significantly enhanced the transport of LDS at pH4.0, the transport of the cation was seen to increase with increasing pH, with maximum effect at pH7.4 for Curcumin. The pH dependent bilayer localization of both the drugs was investigated by conducting steady state FRET studies using DPH labeled lipids as donors. The FRET results and the relative population of the various ionic/nonionic species of the drugs at different pH suggest that distance dependent interaction between the various ionic species of the drugs and polar head groups of the lipid is responsible for the observed pH dependence enhancement of the drug induced membrane permeability. Another interesting observation was that the stability of Curcumin in presence of POPG liposomes was observed to degrade significantly near physiological pH (7.4 and 8.0). Although this degradation did not affect the liposome integrity, interestingly this was observed to enhance the transport of the LDS cation across the bilayer. That the degradation products of Curcumin are equally effective as the drug itself in enhancing the membrane permeability lends additional support to the current opinion that the bioactive degradation products of the drug may have a significant contribution to its observed pharmacological effects.