pH/Thermo-Responsive Grafted Alginate-Based SiO2 Hybrid Nanocarrier/Hydrogel Drug Delivery Systems

Nikolaos Theodorakis; Sofia-Falia Saravanou; Nikoleta-Paraskevi Kouli; Zacharoula Iatridi; Constantinos Tsitsilianis

doi:10.3390/polym13081228

pH/Thermo-Responsive Grafted Alginate-Based SiO₂ Hybrid Nanocarrier/Hydrogel Drug Delivery Systems

Polymers (Basel). 2021 Apr 10;13(8):1228. doi: 10.3390/polym13081228.

Authors

Nikolaos Theodorakis¹, Sofia-Falia Saravanou¹, Nikoleta-Paraskevi Kouli¹, Zacharoula Iatridi¹, Constantinos Tsitsilianis¹

Affiliation

¹ Department of Chemical Engineering, University of Patras, 26500 Patras, Greece.

Abstract

We report the preparation of mesoporous silica nanoparticles covered by layer by layer (LbL) oppositely charged weak polyelectrolytes, comprising poly(allylamine hydrochloride) (PAH) and a sodium alginate, highly grafted by N-isopropylacrylamide/N-tert-butylacrylamide random copolymers, NaALG-g-P(NIPAM₉₀-co-NtBAM₁₀) (NaALG-g). Thanks to the pH dependence of the degree of ionization of the polyelectrolytes and the LCST-type thermosensitivity of the grafting chains of the NaALG-g, the as-prepared hybrid nanoparticles (hNP) exhibit pH/thermo-responsive drug delivery capabilities. The release kinetics of rhodamine B (RB, model drug) can be controlled by the number of PAH/NaALG-g bilayers and more importantly by the environmental conditions, namely, pH and temperature. As observed, the increase of pH and/or temperature accelerates the RB release under sink conditions. The same NaALG-g was used as gelator to fabricate a hNP@NaALG-g hydrogel composite. This formulation forms a viscous solution at room temperature, and it is transformed to a self-assembling hydrogel (sol-gel transition) upon heating at physiological temperature provided that its T_gel was regulated at 30.7 °C, by the NtBAM hydrophobic monomer incorporation in the side chains. It exhibits excellent injectability thanks to its combined thermo- and shear-responsiveness. The hNP@NaALG-g hydrogel composite, encapsulating hNP covered with one bilayer, exhibited pH-responsive sustainable drug delivery. The presented highly tunable drug delivery system (DDS) (hNP and/or composite hydrogel) might be useful for biomedical potential applications.

Keywords: LbL technique; PNIPAM; alginate; hydrogel composite; mesoporous silica; organic/inorganic hybrid; shear thinning injectability; thermo-responsive graft copolymer; thermo-thickening.