Nanostructured Lipid Carriers (NLCs) in Drug Delivery: Recent Advances,Functionalization Strategies, and Clinical Translation

Introduction: Conventional drug delivery systems often face challenges such as poor solubility, first-pass metabolism, and non-specific drug distribution. Nanostructured Lipid Carriers (NLCs), as an advancement over Solid Lipid Nanoparticles (SLNs), offer improved drug loading, stability, and controlled release due to their hybrid lipid matrix. Methods: This review compiles and critically analyzes literature from 2022 to 2024 to highlight advancements in the design, functionalization, and clinical translation of NLCs. Emphasis is placed on structural types of NLCs, preparation techniques, surface modifications (ligandmediated, PEGylation, and stimuli-responsive systems), and route-specific delivery strategies. This review was conducted in accordance with PRISMA 2020. Results: NLCs have demonstrated a significant enhancement in therapeutic efficacy, with some studies reporting a 40-60% increase in oral bioavailability and improved skin penetration for topical drugs compared to conventional formulations. PEGylated and ligand-functionalized NLCs showed greater cellular uptake and barrier penetration, particularly in models of cancer and CNS disorders. Clinical trials with docetaxel-loaded NLCs and NLC-based eye drops have shown better targeting and prolonged therapeutic effect. Discussion: Despite encouraging preclinical and early clinical results, translational challenges persist, including scalability, regulatory clarity, and long-term stability. Standardization in production and advanced characterization techniques are essential for successful clinical adoption. Conclusion: NLCs present a promising solution to the limitations of traditional delivery systems. Their multifunctionality and evolving design platforms position them as next-generation carriers in precision therapeutics, provided regulatory and industrial hurdles are systematically addressed.