Synthesis of Dual Stimuli-Responsive Amphiphilic Particles through Controlled Semi-batch Emulsion Polymerization

The stimuli-responsive multicomponent polymers have several applications in medicine due to their attractive nanostructural features and adaptability to changes in pH and temperature. Researchers from The Hong Kong Polytechnic University led by Professor Pei Li used a one-pot controlled semi-batch emulsion polymerization method to synthesize amphiphilic particle consisting of a hydrophobic component, a pH-sensitive polyethyleneimine and a temperature sensitive poly (N-isopropyl acrylamide).

The work which is now reported in the peer-reviewed journal, Polymer, also included investigations on the structural features of temperature-responsive behavior and surface charge variation of the synthesized dual stimuli-responsive multicomponent  polymer.

In their experiments, following the graft polymerization of N-isopropyl acrylamide from the water-soluble polyethyleneimine in the presence or absence of a crosslinking agent, N,N’-methylene bis(acrylamide), methyl methacrylate and styrene monomers were added to undergo a seeded emulsion polymerization at 80⁰C in a controlled reactor. The one-pot controlled semi-batch emulsion polymerization used by the authors was easy and efficient with high monomer conversion.

It was also found that the seed nanogels of the polymerized polyethyleneimine/poly(N-isopropyl acrylamide) were bigger in average size, but became smaller with narrower particle size distribution after forming multicomponent polymers. The results indicate that the seed nanogels are stable and highly swollen to allow the second stage seeded polymerization.

Further polymerization of styrene and methyl methacrylate monomers into the initially formed poly(N-isopropyl acrylamide) and polyethyleneimine seed nanogels resulted in a decrease in particle size for the resultant multicomponent particles. However, the addition of styrene polymers resulted to a smaller particle size compared to that of methyl methacrylate polymers.

Microscopic images revealed a formed multi-domain nanostructure following the addition of methyl methacrylate monomers into the seed nanogel while that of styrene showed a multilayered structure. An increase in the crosslinking density (2 to 5%) of the seed nanogels of polyethyleneimine/poly(N-isopropyl acrylamide) had some effects on the morphologies of the added methyl methacrylate and styrene monomers.

At different pH levels, the authors discovered that certain concentrations of N-isopropyl acrylamide provided a shielding in the surface charges of multilayered multicomponent particles. This change in concentration was also responsible for the controllable temperature-responsive surface features of the multilayered multicomponent polymers with the absence of crosslinks.

Following the basis that the positive surface charges could lead to cellular uptake, the authors tested cellular uptake of a present fluorescein isothiocyanate isomer 1 in multilayered multicomponent particles with a crosslinking density of 2% into the HeLa cells, and the results obtained supports this assumption. The presence of polyethyleneimine surface layer was believed to facilitate cellular uptake of the nanoparticles.

The authors’ research on the temperature-responsive surface property of the dual stimuli-responsive amphiphilic particles provides an avenue for its effective adaptation into adjustable temperature and pH conditions related to the medical field.