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

Thermally induced aggregation transitions have been investigated for aqueou s solutions of the poloxamine block copolymer T701-(OE4OP13)(2)NCH2CH2N(OP1 3OE4)(2)-using differential scanning calorimetry. The calorimetric signals obtained were fitted to a mass action model description of aggregation usin g a previously reported analytical procedure (Patterson et al., Langmuir 13 (1997) 2219). The presence of a central ethylene diamine moiety in the mol ecular structure renders the T701 molecule basic; this was confirmed and me asured by acid/base titration. Basicity is shown to have an important impac t upon aggregation. At low pH (2.5), the poloxamine exists in its protonate d form and the bulk solution proton concentration is sufficient to suppress de-protonation, aggregation-as a consequence-is shifted to a higher temper ature range. Any increase in pH reduces the temperature range over which ag gregation occurs. The derived experimental calorimetric parameters, obtaine d from model fitting procedures, can be used to compute the fraction of pol oxamine 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 increase s to about 85%. These aggregation characteristics of T701 have important im plications for the design of drug delivery systems, which incorporate polox amines. (C) 2001 Elsevier Science BN. All rights reserved.