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. 2025 Sep;14(9):e202500038.
doi: 10.1002/open.202500038. Epub 2025 Jun 4.

Ibuprofen-Functionalized Alkyl α-hydroxy Methacrylate-Based Polymers

Burcu Balaban  1 , Seckin Altuncu  1 , Aleyna Esenturk  1 , Simay Denizkusu  1 , Ece Sabuncu  2 , Hande Sipahi  2 , Duygu Avci  1
Affiliations

Ibuprofen-Functionalized Alkyl α-hydroxy Methacrylate-Based Polymers

Burcu Balaban et al. ChemistryOpen. 2025 Sep.

Abstract

Novel alkyl α-hydroxymethacrylate-based prodrugs are prepared to improve bioavailability, decrease toxicity, and control drug release. First, an ibuprofen (IBU)-functionalized methacrylate (TBMA-IBU) is synthesized from the reaction of tert-butyl α-bromomethacrylate with IBU. The free radical homopolymerization and copolymerization with poly(ethylene glycol) methyl ether methacrylate (Mn = 300), cleavage of tert-butyl ester groups of the homopolymer and a copolymer with trifluoroacetic acid (TFA) gave new polymer prodrugs (p-TBMA-IBU, p-TBMA-IBU-co-PEGMA, p-MA-IBU, and p-MA-IBU-co-PEGMA), with IBU linked through ester bonds on the side chain. The release studies showed extended-release of IBU (20-60% in 15 d), which can be triggered under the stimulation of lipase. The in vitro studies indicate that the representative polymers are effective in relieving inflammatory responses in RAW264.7 macrophage cells without any cytotoxicity. These results suggest that the synthesized polymers with controllable functionality can be promising IBU prodrugs.

Keywords: alkyl α‐hydroxymethacrylates; drug design; ibuprofen; inflammation; polymer‐drug conjugates.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Synthesis of TBMA‐IBU and its polymer conjugates.
Figure 2
Figure 2
1H NMR spectrum of TBMA‐IBU.
Figure 3
Figure 3
13C NMR spectrum of TBHMA‐IBU.
Figure 4
Figure 4
1H NMR spectra of p‐TBMA‐IBU (top) and p‐MA‐IBU (bottom).
Figure 5
Figure 5
R p versus time and conversion versus time plots of TBMA‐IBU, PEGMA, and TBMA‐IBU:PEGMA (25:75 and 50:50 mol%).
Figure 6
Figure 6
Thermal degradation of p‐TBMA‐IBU, p‐MA‐IBU, and p‐TBMA‐IBU‐co‐PEGMA (50:50 mol%).
Figure 7
Figure 7
The release profiles of IBU from p‐TBMA‐IBU, p‐TBMA‐co‐PEGMA (50:50 mol% in feed) (top), and p‐MA‐IBU with or without lipase (bottom).
Figure 8
Figure 8
The effects of ibuprofen functionalized polymers at various doses (50, 100, and 200 μM) on nitrite production in LPS‐stimulated RAW 264.7 cells. Ctrl: Control group treated with DMEM; LPS: Control group only stimulated with LPS; LPS: Lipopolysaccharides from E. coli; Indomethacin: Indomethacin (100 μM); IBU: Ibuprofen. Statistically significant differences were indicated for each compound versus LPS (*p < 0.001.).
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