The Optimal Amount of PAMAM G3 Dendrimer in Polyurethane Matrices Makes Them a Promising Tool for Controlled Drug Release.

Systemic anticancer therapy causes a number of side effects; therefore, local drug release devices may play an important role in this area. In this study, we developed polyurethane-dendrimer foams containing different amounts of third-generation poly (amidoamine) dendrimers (PAMAM G3) to evaluate their ability to encapsulate and release the model anticancer drug doxorubicin (DOX), as well as their biocompatibility and effectiveness against normal and cancer cells in vitro. PU-PAMAM foams containing 10-50 wt% PAMAM G3 were prepared using glycerin-based polyether polyol and castor oil as co-components. Structural and rheological analyses revealed that foams containing up to 20 wt% PAMAM G3 exhibited a well-developed porous structure, while higher dendrimer loadings (≥30 wt%) led to irregular cell shapes, pore coalescence, and thinning of cell walls, and indicated a gradual loss of structural integrity. Rheological creep-recovery measurements confirmed the structural findings: moderate PAMAM G3 incorporation (≤20 wt%) increased both the instantaneous and delayed elastic modulus (E1 ≈ 130-140 kPa; E2 ≈ 80 kPa) and enhanced elastic recovery, reflecting improved cross-link density and foam stability. Higher dendrimer contents (30-50 wt%) caused a decline in these parameters and higher viscoelastic compliance, indicating a softer, less stable structure. The DOX loading capacity and encapsulation efficiency increased with PAMAM G3 content, reaching maximum values of 35% and 51% for 30-40 wt% PAMAM G3, respectively. However, the most sustained DOX release profiles were observed for matrices containing 20 wt% PAMAM G3. Analysis of cumulative release and kinetic modeling revealed a transition from diffusion-controlled release at low PAMAM contents to burst-dominated release at higher dendrimer loadings. Importantly, matrices containing 10-20 wt% PAMAM G3 also indicated selective anticancer action against squamous cell carcinoma (SCC-15) compared to non-cancerous human keratinocytes (HaCaT). Moreover, the DOX they released effectively destroyed cancer cells. Overall, PU-PAMAM foams containing 10-20 wt% PAMAM G3 provide the most balanced combination of structural stability, controlled drug release, and cytocompatibility. These materials therefore represent a promising platform as passive carriers in drug delivery systems (DDSs), such as local implants, anticancer patches, or bioactive wound dressings.