The influence of amphiphilic quaternary ammonium palmitoyl glycol chitosan (GCPQ) polymer composition on oil-loaded nanocapsule architecture

Hypothesis Predicting the exact nature of the self-assembly of amphiphilic molecules into supramolecular structures is of utmost importance for a variety of applications, but this is a challenge for nanotechnology. The amphiphilic drug delivery polymer-N-palmitoyl-N-monomethyl-N,N-dimethyl-N,N,N-trimethyl-6-O-glycolchitosan (GCPQ) self-assembles in aqueous media to form nanoparticles. Experiment This work aimed to develop a systematic predictive mathematical model on the eventual nature of oil-loaded GCPQ-nanoparticles and to determine the main independent variables that affect their nanoarchitecture following self-assembly. GCPQ polymers were produced with varying degree of palmitoylation (DP, 5.7-23.8 mol%), degree of quaternization (DQ, 7.2-22.7 mol%), and molecular weight (MW, 11.2-44.2 kDa) and their critical hydrophilic-lipophilic balance (cHLB) optimized to produce oil-loaded nanocapsules. Findings Non-linear mathematical models (Particle size (nm) = 466.05 - 5.64DP - 6.52DQ + 0.13DQ(2) - 0.03 MW2 - 14.48cHLB + 0.48cHLB(2)) were derived to predict the nanoparticle sizes (R-2 = 0.998, R-adj(2) = 0.995). Smaller nanoparticle sizes (148-157 nm) were obtained at high DP, DQ, and cHLB values, in which DP was the main independent variable responsible for nanoparticle size. Single or multiple-oil cores with small particles stabilizing polymer shells could be observed depending on the oil volume. Nanoparticle architectures, especially the nature of the oil-core(s), were driven by the DP, DQ, cHLB, and oil concentration. Here, we have developed a predictive model that may be applied to understand the nanoarchitecture of oil-loaded GCPQ-nanoparticles.