Sustained Delivery of Paliperidone Palmitate via Encapsulation in Bio-Based NIPU Nanoparticles

In this study, Paliperidone Palmitate (PP), a second-generation antipsychotic, commonly used for the treatment of schizophrenia, was encapsulated in bio-based non-isocyanate polyurethane (NIPU) nanoemulsions. NIPU was synthesized via an isocyanate-free polyaddition route, addressing safety and environmental concerns associated with conventional polyurethanes. The drug-loaded nanoparticles were produced utilizing oil-in-water (O/W) emulsions followed by solvent evaporation and lyophilization. NIPU concentrations of 0.3% and 0.5% w/v, as well as 0.5% w/v PVA were employed, while PP was incorporated at 0.2%, 0.5% and 1% w/v. The formulations were characterized by FTIR, DSC and XRD analyses, and the mechanical strength of neat sponges was evaluated. The nanoparticle formation and size were assessed by DLS and SEM analyses. The water contact angle, porosity measurements and aquatic and enzymatic hydrolysis were additionally performed. The resulting nanocarriers exhibited controlled particle size, increased drug-loading values, structural stability and biodegradability. Lastly, the in vitro dissolution studies revealed a system-specific burst release behavior, and a controlled and sustained overall drug-release profile for majority of the formulations, thereby indicating the potential of NIPU nanocarriers for drug delivery applications, particularly where sustained therapeutic effects are required.