Advances in Design, Formulation and Pharmacokinetic Evaluation of Targeted Nanostructured Lipid Carriers for Enhanced Oral Bioavailability of Poorly Soluble Antineoplastic Agents

Sarah Jenkins, Kenichi Nomura

Oral administration of hydrophobic antineoplastic drugs is frequently hampered by poor aqueous solubility, extensive first-pass hepatic metabolism, and low gastrointestinal bioavailability. This pharmaceutical study develops, optimizes, and evaluates surface-modified Nanostructured Lipid Carriers (NLCs) engineered for the enhanced oral bioavailability and controlled intestinal release of paclitaxel. The lipid nanoparticles were synthesized via high-pressure hot homogenization utilizing solid and liquid lipid matrices stabilized with non-ionic surfactants and functionalized with chitosan for mucoadhesive targeting. Physicochemical characterization demonstrated uniform spherical morphology with a mean hydrodynamic particle size of 138.4 nanometers, polydispersity index of 0.142, and high drug entrapment efficiency of 92.6%. In vivo pharmacokinetic studies conducted in rodent models confirmed a 4.6-fold enhancement in systemic peak plasma concentration (Cmax) and a 5.2-fold increase in total area under the plasma concentration-time curve (AUC0-inf) compared to standard oral drug suspensions. Cellular cytotoxicity assays against human carcinoma cell lines corroborated enhanced cellular uptake and apoptotic induction, establishing the formulated NLCs as a promising nanocarrier platform for oral cancer chemotherapy.