Polyurethane Foams Functionalized with Hydroxylated PAMAM G3 Dendrimers for Local Drug Delivery, Including Anticancer Therapy: In Vitro and In Vivo Studies

There is growing interest in local drug delivery systems that release their payload in a controlled manner directly at the implantation site. Such systems are particularly valuable in solid tumors, chronic wounds and infections, where systemic administration is constrained by poor tissue penetration and dose-limiting side effects. In this study, hydroxylated poly(amidoamine) (PAMAM) G3 dendrimers were incorporated into polyurethane foams (PU) as multifunctional polyol components to obtain hybrid porous matrices. Surface polyhydroxylation of amine-terminated PAMAM G3 via glycidol ring-opening introduced hydroxyl functionalities that enabled integration of the modified dendrimer into the PU network. Morphological analysis by scanning electron microscopy (SEM) and micro-computed tomography (µCT) confirmed a well-defined cellular architecture without macroscopic defects upon dendrimer incorporation. The modified material exhibited reduced apparent density and increased water absorption compared with the reference PU foam. Rheological creep–recovery analysis demonstrated enhanced delayed elasticity and reduced permanent deformation in the dendrimer-modified matrix, reflecting improved viscoelastic recovery. Mass balance analysis showed higher encapsulation efficiency for the dendrimer-modified foam (34.9%) than for the reference material (29.7%). Despite this higher loading, the cumulative release of doxorubicin (DOX) over 100 h in phosphate-buffered saline (PBS) (pH 7.4, 37 °C) was lower for the modified system (7.0%) than for the reference matrix (15.8%), and the initial burst release after 30 min was six-fold lower, indicating enhanced drug retention and the potential for prolonged release. Biological studies showed that the matrices were non-toxic and highly biocompatible towards human SCC-15 and HaCaT cells in vitro and in the Caenorhabditis elegans model in vivo, whereas DOX released from the matrices effectively killed cancer cells at extract concentrations as low as 3%. These results show that hydroxylated PAMAM G3 acts as a structural modifier of PU foams capable of modulating drug retention and release, and therefore use of dendrimeric matrix as a drug carrier in local therapy is worth considering.