Docetaxel-Loaded Poly(3HB-co-4HB) Biodegradable Nanoparticles: Impact of Copolymer Composition

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Nanotechnology

Background:

• Polyhydroxyalkanoate (PHA) copolymers offer enhanced in vivo degradation rates, making them attractive for medical applications.
• Docetaxel (DCX), a poorly water-soluble anticancer drug, requires effective delivery systems for improved therapeutic outcomes.
• The biosynthesis of P(3HB-co-4HB) copolymers by Cupriavidus malaysiensis USMAA1020 provides a sustainable source for nanoparticle development.

Purpose of the Study:

• To develop and characterize docetaxel-loaded nanoparticles using P(3HB-co-4HB) copolymers with varying 4-hydroxybutyrate (4HB) content.
• To optimize nanoparticle formulation for docetaxel encapsulation and controlled release.
• To evaluate the potential of these nanoparticles for anticancer drug delivery.

Main Methods:

• Three P(3HB-co-4HB) copolymers with 16%, 30%, and 70% 4HB content (PHB16, PHB30, PHB70) were synthesized.
• Nanoparticles were prepared using the emulsification/solvent evaporation method, with Polyvinyl Alcohol (PVA) and Vitamin E-TPGS as stabilizers/surfactants.
• Characterization included particle size, size distribution (PDI), surface charge, encapsulation efficiency, and in vitro drug release studies.

Main Results:

• Optimized formulations using PHB70, PVA, and VitE-TPGS yielded nanoparticles with an average size of ~150 nm and a narrow PDI (<0.100).
• Encapsulation efficiency of docetaxel increased with 4HB content, reaching up to 50% for PHB70 nanoparticles at a 30% drug-to-polymer ratio.
• Docetaxel release profiles showed approximately 60% release within 7 days for lower drug loadings, and nearly complete release (98%) at higher loadings (30-40%) within the same timeframe.

Conclusions:

• P(3HB-co-4HB) copolymers, particularly PHB70, are suitable for developing docetaxel-loaded nanoparticles with controlled size and high encapsulation efficiency.
• The developed nanoparticles demonstrate tunable drug release kinetics, suggesting their potential for effective docetaxel delivery in cancer therapy.
• This study highlights the promise of PHA-based nanoparticles for advanced drug delivery systems in biomedical applications.