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

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 Tgel 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.

Role of Polymer Concentration and Crosslinking Density on Release Rates of Small Molecule Drugs

“…We attribute these differences in SiNP mediated effects on drug release rates (and mechanical properties) to differences in the extent to which the nanoparticles may interact with the polymer chains. While it has been reported that alginate may non-covalently associate with silica nanoparticle surface [41], there are no published works (to the best of our knowledge) demonstrating positive interactions between agarose and silica nanoparticles.…”

“…We attribute these differences in SiNP mediated effects on drug release rates (and mechanical properties) to differences in the extent to which the nanoparticles may interact with the polymer chains. While it has been reported that alginate may noncovalently associate with silica nanoparticle surface [41], there are no published works (to the best of knowledge) demonstrating positive interactions between agarose and silica nanoparticles. Finally, we performed experiments to confirm that the differences in drug release rates were biologically relevant, i.e., differences in drug release rates from the different hydrogel formulations translate to differences in compound-mediated cell viability.…”

Natural Biopolymers as Smart Coating Materials of Mesoporous Silica Nanoparticles for Drug Delivery

“…The coating with alginate is generally achieved by electrostatic interactions between the anionic biopolymers and the MSNs surface, made positive by appropriate functionalization [ 205 ]. Moreover, alginate is used in combination with positive polymers to create composite coatings by the already mentioned LbL self-assembly technique [ 206 , 207 , 208 ]. For instance, two recent studies used alginate in combination with chitosan for the formulation of pH-responsive polyelectrolyte-coated MSNs in the treatment of cancer [ 144 ] and neurodegenerative diseases [ 187 ].…”

Nanoarchitectonics beyond perfect order – not quite perfect but quite useful

“…329,330 Some polyelectrolyte multilayers have pH-dependent ionization degree, near-infrared light, and thermal sensitivity, and the resulting polymers show good pH, light, and thermal responsiveness, which provides a basis for targeted drug release. 331–333…”

“…329,330 Some polyelectrolyte multilayers have pH-dependent ionization degree, near-infrared light, and thermal sensitivity, and the resulting polymers show good pH, light, and thermal responsiveness, which provides a basis for targeted drug release. [331][332][333] 4.2.2 Hydrogels. As mentioned above, self-assembled hydrogels have reliable biocompatibility compared with the hydrogels formed by chemical cross-linking and possess the general properties inherent in hydrogels, including high water content and network-like structure.…”