Unusual Enthalpy Driven Self Assembly at Room Temperature with Chitosan Amphiphiles.

BACKGROUND

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.

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 calorimetry.

RESULTS

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).

CONCLUSION

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.