Nanostructured Lipid Carriers as an Advanced Oral Drug Delivery System for Improving Bioavailability

Oral drug delivery remains the most preferred route of administration due to patient convenience and compliance; however, poor oral bioavailability continues to limit the therapeutic efficacy of many drugs, particularly those belonging to Biopharmaceutics Classification System (BCS) classes II and IV. Factors such as low aqueous solubility, inadequate intestinal permeability, extensive first-pass metabolism, and efflux transporter activity significantly compromise drug absorption following oral administration. To overcome these challenges, lipid-based nanocarrier systems have emerged as promising strategies, among which nanostructured lipid carriers (NLCs) represent a second-generation advancement over solid lipid nanoparticles. NLCs are composed of a blend of solid and liquid lipids stabilized by biocompatible surfactants, resulting in a structurally imperfect lipid matrix that enhances drug loading capacity and minimizes drug expulsion during storage. The unique composition and nanoscale size of NLCs facilitate improved drug solubilization in gastrointestinal fluids, promote lymphatic transport, reduce first-pass hepatic metabolism, and enhance intestinal permeability, collectively leading to improved oral bioavailability. This review provides a comprehensive overview of the principles of oral bioavailability, the relevance of BCS classification, and the design rationale of nanostructured lipid carriers.