The effect of pH and concentration upon aggregation transitions in aqueous solutions of poloxamine T701

Thermally induced aggregation transitions have been investigated for aqueous solutions of the poloxamine block copolymer T701—(OE 4OP 13) 2NCH 2CH 2N(OP 13OE 4) 2—using differential scanning calorimetry. The calorimetric signals obtained were fitted to a mass action model description of aggregation using a previously reported analytical procedure (Patterson et al., Langmuir 13 (1997) 2219). The presence of a central ethylene diamine moiety in the molecular structure renders the T701 molecule basic; this was confirmed and measured by acid/base titration. Basicity is shown to have an important impact upon aggregation. At low pH (2.5), the poloxamine exists in its protonated form and the bulk solution proton concentration is sufficient to suppress de-protonation, aggregation—as a consequence—is shifted to a higher temperature range. Any increase in pH reduces the temperature range over which aggregation occurs. The derived experimental calorimetric parameters, obtained from model fitting procedures, can be used to compute the fraction of poloxamine existing in an aggregated form, at any particular temperature. The data sets obtained were interpolated to show that at human body temperature (310.6 K) the fraction of poloxamine found in its aggregated form is zero at a pH of 2.5. However at a pH of 6.8, the percentage aggregation increases to about 85%. These aggregation characteristics of T701 have important implications for the design of drug delivery systems, which incorporate poloxamines.