| Autor: |
Xiangheng Guan, Xin-Gang Wang, Binbin Sun, Hongsheng Wang, EL-Newehy, Mohamed, Abdulhameed, Meera Moydeen, Xiumei Mo, Bei Feng, Jinglei Wu |
| Zdroj: |
Journal of Materials Chemistry B; 12/21/2024, Vol. 12 Issue 47, p12251-12264, 14p |
| Abstrakt: |
Polymer-drug conjugates are widely used for drug delivery. Herein, we report an injectable hydrogel for local delivery of nonsteroidal anti-inflammatory drugs (NSAIDs) using chitosan (CS) as a carrier polymer. Loxoprofen (LOX) was conjugated to the backbone of CS via carbodiimide chemistry to obtain the LOX-CS conjugate. This conjugation transformed the water-insoluble unmodified CS into the water-soluble LOX-CS conjugate. In particular, the LOX-CS conjugate did not precipitate at pH 7, allowing smooth subsequent chemical modification with methacrylic anhydride (MA) to synthesize LOX- CS methacrylate (LOX-CS-MA) with significantly higher methacrylation substitution. The LOX-CS-MA was capable of in situ gel formation under visible light irradiation in the presence of a benzoin-2,4,6-trimethylbenzoylphosphinate lithium (LAP) photoinitiator. Our results show that the LOX-CS-MA hydrogel exhibited good cytocompatibility and blood compatibility. It promoted M2 polarization, inhibited pro-inflammatory gene expression, and upregulated anti-inflammatory gene expression of macrophages. Furthermore, the LOX-CS-MA hydrogel significantly reduced reactive oxygen species (ROS) and nitric oxide (NO) produced by lipopolysaccharide (LPS)-stimulated macrophages. A subcutaneous implanted LOX-CS-MA hydrogel in a rat model revealed significantly reduced inflammatory cell density, decreased cell infiltration, and a much thinner fibrous capsule compared to the CS methacrylate (CS-MA) hydrogel, thus markedly alleviating the inflammatory response. This study highlights the feasibility of CS-drug conjugates in preparing CS-based methacrylate hydrogels for sustained drug release. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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