Unusual Enthalpy Driven Self Assembly at Room Temperature with Chitosan Amphiphiles

Area of Science:

• Polymer Chemistry
• Materials Science
• Nanotechnology

Background:

• N-palmitoyl-N-monomethyl-N,N-dimethyl-N,N,N-trimethyl-6-O-glycolchitosan (GCPQ) is a self-assembling polymer explored as a pharmaceutical nano-carrier.
• GCPQ nanoparticles facilitate drug transport across biological barriers, enhancing drug efficacy.
• The chemical properties of GCPQ, including hydrophobicity and molecular weight, can be modified.

Purpose of the Study:

• To investigate the thermodynamic principles governing GCPQ self-assembly.
• To determine the influence of polymer molecular weight and hydrophobicity on self-assembly thermodynamics.

Main Methods:

• Isothermal titration calorimetry (ITC) was employed to study GCPQ self-assembly thermodynamics.
• Analysis of micellar aggregate formation and critical micellar concentrations (CMCs).

Main Results:

• GCPQs (Mw = 8-15 kDa) formed micellar aggregates at low concentrations (1-2.4 µM at 25°C).
• Micellization was found to be unusually enthalpy-driven.
• A positive correlation existed between enthalpy of micellization (ΔHmic) and quaternary group content (Q): ΔHmic = 3.8 Q - 159 (r² = 0.93).
• A negative correlation was observed between ΔHmic and molecular weight (Mw): ΔHmic = -13.5 Mw - 26.3 (r² = 0.99).

Conclusions:

• Hydrophobicity and molecular weight are key drivers for stable GCPQ self-assemblies.
• Increased hydrophobicity and molecular weight contribute to a greater enthalpy contribution during micellization.
• These findings offer fundamental insights into the self-assembly behavior of GCPQ for nano-carrier applications.