Odunze Uchechukwu, O'Brien Fionn, Godfrey Lisa, Schätzlein Andreas, Uchegbu Ijeoma
School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, United Kingdom.
Nanomerics, New Bridge Street House, 30-34 New Bridge Street, London, EC4V 6BJ, United Kingdom.
Pharm Nanotechnol. 2019;7(1):57-71. doi: 10.2174/2211738507666190311123401.
GCPQ (N-palmitoyl-N-monomethyl-N,N-dimethyl-N,N,N-trimethyl- 6-O-glycolchitosan) is a self-assembling polymer being investigated as a pharmaceutical nano-carrier. GCPQ nanoparticles shuttle drugs across biological barriers, improving drug performance. The exact chemistry of GCPQ is varied by the relative proportion of hydrophobic (N-palmitoyl) and hydrophilic (quaternary ammonium) groups and molecular weight.
We hypothesised that the thermodynamics of self-assembly is controlled by the polymer molecular weight and hydrophobicity.
The thermodynamics of self-assembly was investigated using isothermal calorimetry.
GCPQs (Mw = 8-15 kDa) formed micellar aggregates at critical micellar concentrations of 1-2.4 µM at 25°C and micellisation was unusually enthalpy driven. There was a positive correlation between ΔHmic and mole% quaternary groups (Q): ΔHmic = 3.8 Q- 159 (r2 = 0.93) and a negative correlation between ΔHmic and molecular weight (Mw): ΔHmic = -13.5 Mw-26.3 (r2 = 0.99).
These findings provide insights into the positive drivers of stable selfassemblies, namely hydrophobicity and molecular weight, as both hydrophobicity and molecular weight are associated with an increased enthalpy contribution to micellisation.
GCPQ（N-棕榈酰-N-单甲基-N，N-二甲基-N，N，N-三甲基-6-O-乙二醇壳聚糖）是一种正在作为药物纳米载体进行研究的自组装聚合物。GCPQ纳米颗粒可使药物跨越生物屏障，提高药物性能。GCPQ的确切化学性质因疏水基团（N-棕榈酰）和亲水基团（季铵）的相对比例以及分子量而异。
我们假设自组装的热力学受聚合物分子量和疏水性控制。
使用等温滴定量热法研究自组装的热力学。
GCPQ（分子量 = 8 - 15 kDa）在25℃下临界胶束浓度为1 - 2.4 μM时形成胶束聚集体，胶束化异常地由焓驱动。胶束化焓（ΔHmic）与季铵基团摩尔百分比（Q）之间存在正相关：ΔHmic = 3.8Q - 159（r2 = 0.93），且ΔHmic与分子量（Mw）之间存在负相关：ΔHmic = -13.5Mw - 26.3（r2 = 0.99）。
这些发现揭示了稳定自组装的正向驱动因素，即疏水性和分子量，因为疏水性和分子量都与胶束化的焓贡献增加有关。
