Lipid-based nanocarriers for oral drug delivery enhancement

Oral drug delivery remains the most widely used form because of its non-invasive nature, and high patient compliance. The therapeutic efficacy of oral drugs is limited by lower aqueous solubility, low intestinal permeability, instability within the gastrointestinal (GI) tract, and extensive first-pass hepatic metabolism. These challenges are particularly significant for Biopharmaceutics Classification System (BCS) class II and IV drugs, as well as for biomacromolecules such as peptides and proteins, which are sensitive to enzymatic degradation and show minimal absorption. Consequently, achieving maximum bioavailability and consistent pharmacokinetic profiles through regular oral formulations remains a major challenge in pharmaceutical development. Currently, various formulation, use particle size reduction, salt formation, and use of solubilizing particles, to improve oral drug delivery. However, these methods provide limited and inconsistent outcomes. Nanotechnology-based drug delivery systems, particularly lipid-based nanocarriers, are now majorly used because of their bioactivity, biodegradability, and are able to improve drug solubilization. Oral drug delivery has showed promise with lipid-based systems such liposomes, solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLCs), self-emulsifying drug delivery systems(SEDDS), and ionizable lipid nanoparticles. This help improve the drug absorption through several mechanisms, including enhanced dissolution, protection from GI degradation, modulation of intestinal permeability, and lymphatic transport. Limitations including formulation instability, scalability challenges, variability in in-vivo performance, and regulatory concerns related to safety and toxicity continue to restrict the clinical use of the nanocarriers. The aim of this review is to analyze the role of lipid-based nanocarriers in improving oral drug delivery, with focus on their classification, mechanisms, formulation strategies, and pharmaceutical applications.