Polypeptide-Based Aerosol Nanoparticles: Self-Assembly and Control of Conformation by Solvent and Thermal Annealing

Nanoconfined self-assemblies within aerosol nanoparticles and control of the secondary structures are shown here upon ionically complexing poly(L-lysine) (PLL) with dodecylbenzenesulfonic acid (DBSA) surfactant and using solvents chloroform, 1-propanol, or dimethylformamide. Different solvent volatilities and drying temperatures allowed tuning the kinetics of morphology formation. The supramolecular self-assembly and morphology were studied using cryo-TEM and SEM, and the secondary structures, using FT-IR. Highly volatile chloroform led to the major fraction of alpha-helical conformation of PLL(DBSA), whereas less volatile solvents or higher drying temperatures led to the increasing fraction of beta-sheets. Added drugs budesonide and ketoprofen prevented beta-sheet formation and studied PLL(DBSA) drug nanoparticles were in the alpha-helical conformation. Preliminary studies showed that ketoprofen released with a slower rate than budesonide which was hypothesized to result from different localization of drugs within the PLL(DBSA) nanoparticles. These results instruct to prepare polypeptide aerosol nanoparticles with internal self-assembled structures and to control the secondary structures by aerosol solvent annealing, which we foresee to be useful, e.g., toward controlling the release of poorly soluble drug molecules.