Central Composite Design Based Optimization of Carbohydrate Coated Albumin Nanoparticles for HCC: Synthesis, Extensive Characterization and In Vivo Pharmacokinetic Evaluation
Sanya Batheja, Rakesh K. Sahoo, Sarita Rani, Shruti Gupta, Kiran K. Tejavath, Sonal Sinha, Ajazuddin, Awesh K. Yadav, Amit Kumar Goyal, Umesh Gupta
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引用次数: 0
Abstract
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.
期刊介绍:
Founded in 1963, Biopolymers publishes strictly peer-reviewed papers examining naturally occurring and synthetic biological macromolecules. By including experimental and theoretical studies on the fundamental behaviour as well as applications of biopolymers, the journal serves the interdisciplinary biochemical, biophysical, biomaterials and biomedical research communities.