Long-term release of clodronate from biodegradable microspheres

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Nanotechnology

Background:

• Biodegradable microparticulate systems offer controlled release for treating bone diseases.
• Bisphosphonates like clodronate are crucial for managing skeletal conditions.
• Optimizing drug encapsulation and release kinetics is key for therapeutic efficacy.

Purpose of the Study:

• To formulate biodegradable microparticles encapsulating clodronate.
• To investigate the impact of polymer type (PLGA, PDLLA) and formulation variables on clodronate release.
• To achieve tunable drug release profiles for bone disease treatment.

Main Methods:

• Fabrication of clodronate-loaded microspheres using poly(D,L-lactide-co-glycolide) (PLGA) and poly(D,L-lactide) (PDLLA) via w/o/w double emulsion solvent evaporation.
• Evaluation of critical process parameters and additives (e.g., Span 20, carboxymethylcellulose) on encapsulation efficiency and release rate.
• Characterization of microsphere morphology, yield, and drug release kinetics.

Main Results:

• Well-formed clodronate microspheres were produced with yields above 60% and encapsulation efficiencies of 49-75%.
• PLGA microspheres exhibited rapid clodronate release (approx. 48 hours), while PDLLA microspheres showed sustained release (approx. 20 days).
• Inclusion of surfactants or viscosifying agents extended release up to 3 months.

Conclusions:

• Biodegradable PLGA and PDLLA microspheres effectively encapsulate clodronate.
• Drug release duration can be precisely modulated from short-term to extended periods (up to 3 months) by selecting appropriate polymers, additives, and manufacturing conditions.
• This tunable drug delivery system holds promise for managing bone diseases effectively.