(T1330-12-68) Folic Acid Conjugated Lipid Nanoparticles containing CORM-2 for Inflammation-Targeted Carbon Monoxide Delivery

Purpose: The aim of this study was to investigate folic acid-modified lipid nanoparticles containing carbon monoxide releasing molecule-2 (FA-CORM-2-LNs) for targeted delivery of carbon monoxide to macrophages

Methods: FA-CORM-2-LNs were prepared by nanotemplate engineering technique with palmityl alcohol as a solid lipid and Tween40/Span40/Myrj S40 as a surfactants mixture. The physical properties of FA-CORM-2-LNs were characterized in terms of particle size, polydispersity index, zeta potential and transmission electron microscopy. The incorporation efficiency of CORM-2 into FA-CORM-2-LNs was determined by quantifying ruthenium using ICP-AES. CO release from FA-CORM-2-LNs were assessed by myoglobin assay. In vitro cytotoxicity of FA-CORM-2-LNs was evaluated with the MTT assays. In vitro anti-inflammatory effects were evaluated by nitric oxide assay in lipopolysaccharide-stimulated RAW 264.7 macrophages. The targeting ability of FA-CORM-2-LNs was evaluated by competitive inhibition assay after pretreatment with free folic acid.

Results: Spherical FA-CORM-2-LNs were around 100 nm with narrow particle size distribution. About 90% of CORM-2 was incorporated into FA-CORM-2-LNs. The sustained CO release from FA-CORM-2-LNs was observed and the half-life of CO release increased up to 30 times compared with that of CORM-2 solution. Non-cytotoxicity of FA-CORM-2-LNs was confirmed by evaluating in vitro cell viability of RAW 264.7 macrophages by MTT assay. Through targeting to Raw 264.7 cells, FA-CORM-2-LNs exhibited better effects than CORM-2-LNs in NO inhibition, suggesting greater anti-inflammatory activity. Taken together, FA-CORM-2-LNs have a great potential for targeted CO therapeutics against inflammation via folate receptor-mediated specific delivery.

Conclusion: These results suggest that folate receptor-targeted lipid nanoparticles containing CORM-2 (FA-CORM-LNs) showed a potential for targeted anti-inflammatory therapy.

References: Foresti R, Bani-Hani MG, Motterlini R. Intensive Care Med 2008:649-58
Qureshi OS, Kim HS, Zeb A. Journal of microencapsulateion 2017:250-61
Yi Ys. Immune Netw 2016:337-43

TEM images of blank-LNs, CORM-2-LNs, and FA-CORM-2-LNs



Comparison of CO release between Fol-CORM-2-NPs, CORM-2-NPs and CORM-2 solution



in vitro anti-inflammatory effects of Fol-CORM-2-NPs, CORM-2-NPs and CORM-2 solution in RAW 264.7 cells