Integrative nanoparticulate strategies with SEDDS for controlled drug release: from lipid platforms to smart delivery systems

Background: Self-emulsifying drug delivery systems (SEDDS) have emerged as effective oral formulation strategies for enhancing the solubility and bioavailability of poorly water-soluble drugs. These systems spontaneously form fine oil-in-water emulsions upon contact with gastrointestinal fluids, thereby facilitating drug absorption. However, conventional SEDDS formulations face challenges, including drug precipitation, formulation instability, and limited targeting efficiency. The integration with nanotechnology has shown promise in overcoming these limitations and improving the performance and functionality of SEDDS. Area covered: This review provides a comprehensive analysis of recent advancements in nano-enabled SEDDS, emphasizing strategies to enhance formulation stability, control release kinetics, and improve targeting ability. Key technologies include solid lipid nanoparticles, polymeric nanocarriers, ion-sensitive gels, and Janus nanoparticles. Each offers distinct advantages, including enhanced mucosal adherence, improved lymphatic transport, and modulated permeability across epithelial barriers. Applications across diverse therapeutic categories, including oncology, virology, central nervous system disorders, and biologics, are examined in depth. Furthermore, preclinical data on bioavailability, pharmacokinetics, and safety are also presented, along with considerations for scalability and regulatory compliance. Expert opinion: Nanoparticle-integrated SEDDS constitute a next-generation oral drug delivery platform that addresses several limitations of traditional lipid-based systems. Despite their therapeutic potential, challenges remain, including formulation complexity, variability in in vivo performance, and the absence of standardized regulatory frameworks. Furthermore, the incorporation of stimuli-responsive features, biomimetic elements, and artificial intelligence-driven formulation optimization is expected to transform future drug delivery designs. Continued interdisciplinary efforts are essential to enable the clinical translation of nano-augmented SEDDS platforms for precision and patient-centered therapies.