Toxicological and anti-inflammatory activities of doxorubicin loaded onto pH-sensitive poly(β-amino ester) modified mesoporous silica nanoparticles in mice.

Chemotherapy drugs used in inflammatory disorders and some cancers, while effective, often cause diverse side toxic effects, prompting research into alternatives to ameliorate damage in healthy tissues. One strategy is to encapsulate doxorubicin (DOX) chemotherapeutic agents into nano-vehicles, such as organic-functionalized mesoporous nanoparticles, to reduce systemic leakage and adverse effects, such as inflammation. This study analyzes the toxicological and anti-inflammatory effects of a drug-delivered system (DDS) based on MCM-41 mesoporous silica nanoparticles modified with a pH-sensitive poly(β-amino ester) named MCM-41-PbAE. The effects of both blank nanoparticles (MCM-41-PbAE) and those with encapsulated DOX (MCM-41-PbAE-DOX) were evaluated in LPS-stimulated mouse macrophages and in an in vivo inflammation model. Characterization of nanoparticles was carried out through TEM, DLS, FTIR Z-potential, and thermogravimetric tests. Macrophages were treated with MCM-41-PbAE and MCM-41-PbAE-DOX particles at several concentrations, and the production of proinflammatory and anti-inflammatory cytokines, nitric oxide (NO), and hydrogen peroxide (HO) levels were determined. Toxicological evaluation was performed in BALB/c mice and the in vivo anti-inflammatory effect was evaluated in a carrageenan-induced paw edema model and the measuring serum levels of pro-inflammatory cytokines. Results indicated that MCM-41-PbAE-DOX significantly reduces NO and HO levels and pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) in dose-manner without affecting cell viability or causing toxicity in mice. Conversely, a reduction in carrageenan-induced paw edema and decreased levels of proinflammatory cytokines were noted, indicating the potential advantage of encapsulating DOX within MCM-41-PbAE nanoparticles, which could inhibit inflammation without compromising healthy cell viability.