Biodegradable Simvastatin-Containing Polymeric Prodrugs with Improved Drug Release

Area of Science:

• Polymer Chemistry
• Biomaterials Science
• Drug Delivery

Background:

• Polymeric prodrugs enhance drug loading but can exhibit slow release due to hydrophobicity.
• Simvastatin polymeric prodrugs previously showed high drug loading but limited in vitro drug release.

Purpose of the Study:

• To accelerate the in vitro degradation and drug release of simvastatin polymeric prodrugs.
• To investigate the effect of incorporating glycolide and lactide comonomers into the polymer backbone.

Main Methods:

• Copolymers were synthesized via ring-opening polymerization using poly(ethylene glycol) as a microinitiator.
• Simvastatin was incorporated, along with either lactide or glycolide comonomers.
• In vitro degradation, drug release, and compressive modulus were evaluated.

Main Results:

• Incorporating glycolide significantly increased in vitro mass loss (up to 2x) and simvastatin release (up to ~7x) compared to parent polymers.
• Glycolide incorporation also led to a 2-3x increase in compressive modulus.
• Lactide-containing polymers showed less pronounced changes compared to glycolide-modified ones.

Conclusions:

• Chemical modification of the polymer backbone by introducing glycolide comonomers effectively accelerates simvastatin release from polymeric prodrugs.
• This strategy improves both the degradation profile and mechanical properties of the simvastatin delivery system.
• Glycolide is a promising comonomer for developing advanced simvastatin polymeric prodrugs with enhanced therapeutic potential.