Armstrong J K, Chowdhry B Z, Snowden M J, Dong J, Leharne S A
Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Int J Pharm. 2001 Oct 23;229(1-2):57-66. doi: 10.1016/s0378-5173(01)00816-x.
Thermally induced aggregation transitions have been investigated for aqueous solutions of the poloxamine block copolymer T701-(OE(4)OP(13))(2)NCH(2)CH(2)N(OP(13)OE(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.
利用差示扫描量热法研究了泊洛沙明嵌段共聚物T701-(OE(4)OP(13))(2)NCH(2)CH(2)N(OP(13)OE(4))(2)水溶液的热致聚集转变。使用先前报道的分析程序（Patterson等人，《朗缪尔》13 (1997) 2219）将获得的量热信号拟合为聚集的质量作用模型描述。分子结构中存在中心乙二胺部分使T701分子呈碱性；通过酸碱滴定对此进行了确认和测量。结果表明碱性对聚集有重要影响。在低pH值（2.5）下，泊洛沙明以质子化形式存在，本体溶液中的质子浓度足以抑制去质子化，因此聚集转移到更高的温度范围。pH值的任何增加都会降低发生聚集的温度范围。从模型拟合程序获得的推导实验量热参数可用于计算在任何特定温度下以聚集形式存在的泊洛沙明的比例。对获得的数据集进行插值表明，在人体温度（310.6 K）下，在pH值为2.5时以聚集形式存在的泊洛沙明比例为零。然而，在pH值为6.8时，聚集百分比增加到约85%。T701的这些聚集特性对包含泊洛沙明的药物递送系统的设计具有重要意义。
