Cancer remains a major global health challenge, and although chemotherapy is widely used for its treatment, the oral administration of anticancer drugs is often limited by poor bioavailability. Factors such as low aqueous solubility, limited intestinal permeability, extensive first-pass metabolism, and active efflux mechanisms significantly reduce the amount of drug reaching systemic circulation. These limitations lead to inconsistent therapeutic outcomes and reduced clinical efficacy. Despite these challenges, oral drug delivery is highly desirable due to improved patient compliance, convenience, and reduced healthcare burden. Recent advancements in nanotechnology have introduced lipid–polymer hybrid nanoparticles (LPHNs) as an effective strategy to overcome these barriers. LPHNs combine the structural stability and controlled-release properties of polymeric nanoparticles with the biocompatibility and solubilization capacity of lipid-based systems. Their core–shell architecture enables efficient drug encapsulation, protection from gastrointestinal degradation, enhanced solubility, and improved intestinal absorption. Additionally, LPHNs can facilitate lymphatic transport, thereby reducing first-pass metabolism and enhancing systemic availability. Surface modification of LPHNs with targeting ligands further improves tumor-specific drug delivery while minimizing off-target toxicity. Preclinical studies have demonstrated significant improvements in pharmacokinetic profiles, bioavailability, and therapeutic efficacy of various anticancer agents when delivered through LPHNs. Although challenges such as large-scale production and long-term stability remain, LPHNs represent a promising platform for oral cancer therapy. Continued research in formulation optimization and clinical translation is essential to fully realize their potential in improving anticancer treatment outcomes.
Chandel et al. (Mon,) studied this question.