Ibuprofen-Functionalized Alkyl α-hydroxy Methacrylate-Based Polymers.

Area of Science:

• Polymer Chemistry
• Drug Delivery Systems
• Biomaterials

Background:

• Improving drug bioavailability and reducing toxicity are key challenges in pharmaceutical development.
• Polymer-based prodrugs offer a versatile platform for controlled drug release and targeted delivery.
• Alkyl α-hydroxymethacrylate-based polymers present a novel scaffold for drug conjugation.

Purpose of the Study:

• To synthesize and characterize novel ibuprofen (IBU)-functionalized methacrylate-based polymer prodrugs.
• To evaluate the drug release kinetics, particularly lipase-triggered release.
• To assess the in vitro efficacy and cytotoxicity of the developed polymer prodrugs for anti-inflammatory applications.

Main Methods:

• Synthesis of an ibuprofen-functionalized methacrylate monomer (TBMA-IBU).
• Free radical polymerization (homo- and co-polymerization with PEGMA) to create polymer prodrugs.
• Chemical cleavage of protecting groups and characterization of the final polymer structures.
• In vitro drug release studies under varying conditions (e.g., lipase stimulation).
• In vitro evaluation of anti-inflammatory activity and cytotoxicity in macrophage cell lines.

Main Results:

• Successfully synthesized and characterized four types of polymer prodrugs: p-TBMA-IBU, p-TBMA-IBU-co-PEGMA, p-MA-IBU, and p-MA-IBU-co-PEGMA.
• Demonstrated extended release of ibuprofen (20-60% over 15 days), controllable by lipase.
• Exhibited significant anti-inflammatory effects in RAW264.7 macrophage cells with no observed cytotoxicity.
• IBU is effectively linked via ester bonds in the polymer side chains, enabling controlled release.

Conclusions:

• Novel methacrylate-based polymer prodrugs effectively deliver ibuprofen with controlled release kinetics.
• The developed prodrugs show potential for managing inflammatory conditions due to their efficacy and safety profile.
• These functional polymers represent a promising strategy for advanced drug delivery systems.