Significant changes in the hydrated size of PP1 Polybee and Lipobee upon incubation with sodium dodecyl sulfate was observed but not a lower pH. This pointed to the anionic membrane interaction as the responsible factor inside the cytoplasm as a plausible melittin release mechanism. Breast cancer cells of a different estrogen receptor status were used as model invitro cancers for growth inhibitions studies. Irrespective of the cell line, Polybees were found to be better anti-cancer formulations compared to Lipobee and free melittin control. DLS results clearly show the variation in size of Lipobee and Polybee only in presence of SDS without any significant effect at a lower pH. It supports the plausible occurrence of anionic interaction in an Meptazinol hydrochloride endosomal compartment responsible for melittin release from Polybee and Lipobee. Additionally, a higher change in size of Lipobee occurred upon incubation with SDS signifying a higher lipid-surfactant interaction. Peptide-polynucleotide interactions have always attracted the interest of medicinal chemists. It is of special interest to decipher melittin DNA interactions and understand their role in dissociation from the DNA secondary structure. Gel electrophoresis was performed to enable observation of the changes in electrophoretic mobility patterns of pBR322 incubated with various for mulations in the presence and in the absence of melittin as well as various concentrations of free melittin. It was found that only free melittin was able to dissociate the plasmid DNA. In turn, the loss of the electrophoresis band was accomplished either by retarding the DNA migration or by expelling the intercalated EtBr due to major groove binding of melittin in the DNA duplex. For mulations with protected melittin in either of the cases, Lipobee and Polybee, did not influence the DNA bands to any significant extent. A further gel electrophoresis investigation showed that ~0.05 ��M free melittin was sufficient to start the dissociation of a DNA secondary structure. The interactions of melittin with DNA in free form signify that a release from Lipobee and Polybee can target genomic DNA, which might extend to the level of hindering the transcription process. However, no interaction can take place if melittin is stably in curporated.