Rifampicin Polymeric Nanoparticles for Tuberculosis: Molecular Dynamics, Physicochemical Characterization and Cytotoxicity

Abstract Tuberculosis infected 10.8 million people worldwide in 2023, resulting in 1.09 million deaths. Rifampicin (RIF) is one of the main drugs used in the treatment, but its low solubility and side effects, such as hepatotoxicity, limit its therapeutic efficacy. Polymeric nanoparticles (PNs) emerge as a promising strategy to optimize RIF delivery. This study aimed to develop RIF-PNs guided by molecular dynamics (MD), perform their physicochemical characterization and evaluate their in vitro cytotoxicity. MD allowed observing the molecular interactions between the components of the formulation and led to the formation of PNs. The PNs presented an average size of 177.0 ± 0.80 nm, polydispersity index of 0.094 ± 0.046, zeta potential of -15.0 ± 0.65 mV, encapsulation efficiency of 20.98% and drug loading of 2.29%, with colloidal stability maintained for up to 180 days. The physicochemical characterizations indicated the polymorphic form II of RIF, amorphous pattern of ethylcellulose (EC) and encapsulation of RIF in PN. Atomic force microscopy observed a spherical shape of the particles with a size of 38.4 ± 14.6 nm. RIF-EC-PN presented a sustained release profile with release of 20.65 ± 0.44% in 24 h and and the unencapsulated RIF demonstrated a release of 90.75% in 15 min. Cell viability was demonstrated in monkey renal epithelial cells (LLC-MK2). PNs showed favorable properties as RIF delivery systems. Graphical Abstract