Unusual Enthalpy Driven Self Assembly at Room Temperature with Chitosan Amphiphiles

BACKGROUND: GCPQ (N-palmitoyl-N-monomethyl-N,N-dimethyl-N,N,N-trime-thyl-6-O-glycolchitosan) is a self-assembling polymer being investigated as a pharmaceu-tical 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 molecu-lar weight. OBJECTIVE: We hypothesised that the thermodynamics of self-assembly is controlled by the polymer molecular weight and hydrophobicity. METHOD: The thermodynamics of self-assembly was investigated using isothermal calo-rimetry. RESULTS: GCPQs (Mw = 8-15 kDa) formed micellar aggregates at critical micellar concen-trations 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). CONCLUSION: These findings provide insights into the positive drivers of stable self-assemblies, namely hydrophobicity and molecular weight, as both hydrophobicity and molecular weight are associated with an increased enthalpy contribution to micellisation.