EFFECT OF LAMOTRIGINE SOLID DISPERSIONS ON VIABILITY OF A549 AND RG-2 CELLS

Objective: LMT is an antiepileptic drug that is among the drugs being repositioned/reprofiled beyond its original medical indications, thanks to its promising anticancer activity profiles on various cancer cells. In this study, the improvement of the poor aqueous solubility of LMT using solid dispersion technique with different polymeric/surfactant carriers in different ratios and the antiproliferative effect potentials of the obtained optimum LMT solid dispersion on A549 and RG-2 cells were determined. Material and Method: LMT solid dispersions were prepared using four different carrier types (PEG 4000, PEG 6000, poloxamer 188 and poloxamer 407) and five different drug to carrier ratios (1:2 - 1:4 - 1:6 - 1:8 - 1:10) according to the melting method and the change in the solubility profile was determined by solubility studies performed according to the shake-flask method. The MTT assay protocol was used to determine the cytotoxicity profile of the selected optimum solid dispersion (F8) on A549 and RG-2 cell lines. The interaction of LMT with the formulation components and the solid-state characteristics within the formulation were evaluated by XRD, DSC, FTIR, and SEM analyses. Result and Discussion: The solubility studies showed that LMT exhibits a pH-dependent solubility profile, and the highest solubility increase (2.3 fold) in solid dispersion formulations was obtained with the F8 formulation using poloxamer 407 at a 1:6 ratio. XRD, DSC, FTIR, and SEM analysis results explain the partial amorphization of LMT in the F8 formulation. In vitro cytotoxicity studies have shown that LMT has a dose-dependent antiproliferative effect on RG-2 cells, but no significant cytotoxic effect at low doses (10-80 µg/ml). For A549 cells, cell viability decreased with increasing doses, suggesting promising results regarding antiproliferative effects at higher doses.