Surprisingly, retention of the peptide within the formulation was not achieved as well as in other published reports of thermo-responsive liposomal formulations, with up to 25% released in the first 8h incubated at RT. It was hypothesised that improvements may be achieved by replacing the counter-ion used in the hydrophobic ion pairing (currently SDS). The impact of counter-ion employed for HIP formation was shown to determine the release in similar delivery systems. Indeed, Bonengel et al. observed counter-ion dependent release profiles for octreotide from self-emulsifying drug delivery systems . Ristroph et al. discovered that the nature of the counter-ion strongly influenced the resulting internal ordering of polymyxin B ion-pair loaded nanocarriers . The authors further demonstrated that the internal ordering strongly impacted the release of polymyxin B from the nanocarriers, with more ordered phases resulting in a slower release Additionally, we hypothesised that the presence of free SDS (from unentrapped and dissociated ion-pairs) may result in solubilisation of the lipid bilayers, resulting in the presence of mixed micelles and further contributing to premature release of teriparatide . Sudbrack et al. demonstrated that the formation of mixed micelles is concentration dependent, where at low concentrations SDS will be incorporated into the bilayer up until a saturation point. Following saturation, the SDS rich bilayer will co-exist with mixed micelles. Finally, above the solubility limit, complete disappearance of the bilayer is obtained and only mixed micelles will be present . This hypothesis was investigated by preparing liposomes of different ion-pair loadings and observing the formulations by cryo-transmission electron microscopy (cryo-TEM).