Docetaxel-Loaded Chitosan-Cholesterol Conjugate-Based Self-Assembled Nanoparticles for Overcoming Multidrug...

Area of Science:

• Biomaterials Science
• Nanotechnology
• Cancer Biology

Background:

• Multidrug resistance (MDR) significantly limits the efficacy of chemotherapy.
• Docetaxel is a key chemotherapeutic agent often rendered ineffective by MDR.
• Novel drug delivery systems are needed to overcome MDR and enhance anticancer drug uptake.

Purpose of the Study:

• To develop cholesteryl hemisuccinate (CHS)-conjugated chitosan (CS)-based self-assembled nanoparticles (NPs).
• To enhance the intracellular uptake of docetaxel in multidrug resistance (MDR)-acquired cancer cells.
• To evaluate the potential of CHS-CS NPs for overcoming MDR in cancer drug delivery.

Main Methods:

• Synthesis and characterization of CHS-CS nanoparticles.
• Assessment of particle size, zeta potential, and drug entrapment efficiency.
• In vitro drug release studies at different pH conditions (6.0 and 7.4).
• In vitro anti-proliferation and cellular accumulation studies in MDR-acquired KBV20C cells.

Main Results:

• Optimized CHS-CS NPs exhibited a mean hydrodynamic diameter of 303 nm and a positive zeta potential of 21.3 mV.
• Docetaxel release from CHS-CS NPs was enhanced in acidic conditions (pH 6.0), mimicking the tumor microenvironment.
• Docetaxel-loaded CHS-CS NPs demonstrated superior anti-proliferative effects and cellular accumulation compared to docetaxel solution in MDR cells.

Conclusions:

• CHS-CS nanoparticles are successfully synthesized and possess suitable characteristics for drug delivery.
• The developed CHS-CS NPs effectively enhance docetaxel uptake in MDR cancer cells.
• CHS-CS NPs show significant potential as a strategy to overcome multidrug resistance in anticancer therapy.