Exploring the Impact of Nanocarrier Composition in Thermo-responsive Hydrogels

Personalized medicine increasingly requires drug delivery systems that can be adapted to specific therapeutic needs while maintaining formulation simplicity and reproducibility. In this context, thermoresponsive hydrogels are attractive because they combine injectability, in situ gel formation and sustained release of entrapped compounds. Their coupling with nanocarriers may further increase the versatility of these systems by modulating their physicochemical properties and drug release behavior.

Based on this, two thermoresponsive nanocomposite formulations were investigated in order to evaluate the influence of nanocarrier composition and surface properties.

Initially, poloxamer 407 (P407), one of the most widely investigated thermoresponsive copolymers for drug delivery, was combined with liposomes characterized by different lipid composition and surface properties. The inclusion of liposomes preserved the thermogelation and viscoelastic behaviour of hydrogels, whereas physical stability was strongly influenced by the vesicular composition and surface architecture, with charged and PEGylated systems showing greater stability than neutral formulations. These differences may reflect distinct liposome-matrix interactions, including hydrophobic interactions between P407 domains and lipid bilayers.

Successively, the same approach was applied to poloxamine 908 (P908), an X-shaped amphiphilic copolymer characterized by both temperature- and pH-responsive behaviour. P908 was combined with nanoparticles made up of poly(lactic-co-glycolic acid) (PLGA) or zein, stabilized with poloxamer 188 (P188) or sodium deoxycholate (SD). The polymer and stabilizer employed significantly modulated the main properties of P908 matrix. Zein nanoparticles prepared with different stabilizers promoted distinct effects on network strength, sol-gel transition and dissolution; in detail, SD-stabilized zein nanoparticles exerted the most pronounced changes in hydrogels, while the Zeta-potential of the colloidal systems affected their drug release, especially under acidic conditions.

These findings demonstrate that nanocarrier-matrix compatibility is a key factor of nanocomposite hydrogels, supporting the design of responsive local drug delivery systems tailored to different therapeutic needs.