Central Composite Design Based Optimization of Carbohydrate Coated Albumin Nanoparticles for <scp>HCC</scp>: Synthesis, Extensive Characterization and In Vivo Pharmacokinetic Evaluation

Hepatocellular carcinoma (HCC) is one serious cause of cancer-associated deaths worldwide. Poor bioavailability and non-specific targeting of drugs is a challenge. Gemcitabine (GEM) is broad-spectrum anticancer drug for liver and other cancers. In this study, an attempt to formulate drug-loaded galactosylated albumin-based nanoparticles (GEM-LA-BSA NPs) was made to increase the bioavailability and targetability of hydrophilic drugs. The formulation was optimized using central composite design for further evaluation and developed a pilot-scale approach for commercialization. LA-BSA conjugate was synthesized, characterized, and formulated into a nanoformulation. The particle size of the optimal formulation was 40.19 ± 7.98 nm with reduced drug release (57.78% ± 4.10%) in 48 h and aggregates-like structure by HR-TEM. In vitro studies in HepG2 cells indicated better cytotoxicity of GEM-LA-BSA NPs than GEM (IC₅₀ values 226.42 ± 11.32 and 366.03 ± 11.93 μg/mL, respectively), while in vivo studies in SD rats exhibited almost two-fold bioavailability, better pharmacokinetics, and reduced IC50 portraying immense potential as an effective drug delivery system.