title: Controlled release of sphingosine-1-phosphate agonist with gelatin hydrogels for macrophage recruitment.
abstract: The objective of this study is to design a drug delivery system (DDS) for the in vivo promotion of macrophage recruitment. As the drug, a water-insoluble agonist of sphingosine-1-phosphate type 1 receptor (SEW2871) was selected. SEW2871 (SEW) was water-solubilized by micelle formation with gelatin grafted by L-lactic acid oligomer. SEW micelles were mixed with gelatin, followed by dehydrothermal crosslinking of gelatin to obtain gelatin hydrogels incorporating SEW micelles. SEW was released from the hydrogels incorporating SEW micelles in vitro and in vivo. The water-solubilized SEW showed in vitro macrophage migration activity. When implanted into the back subcutis or the skin wound defect of mice, the hydrogel incorporating SEW micelles promoted macrophage migration toward the tissue around the implanted site to a significantly great extent compared with SEW-free hydrogel and that mixed with SEW micelles. The hydrogel is a promising DDS to enhance macrophage recruitment in vivo.
authors.affiliation: Department of Biomaterials, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Murakami
authors.affiliation: Department of Biomaterials, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Saito
authors.affiliation: Department of Biomaterials, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan. Electronic address: yasuhiko@frontier.kyoto-u.ac.jp.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tabata
mesh_terms: D000818:Animals; D002417:Cattle; D002452:Cell Count; D002465:Cell Movement / Q000187:drug effects; D003692:Delayed-Action Preparations; D005780:Gelatin / Q000737:chemistry*; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D019344:Lactic Acid / Q000737:chemistry; D008246:Lysophospholipids / Q000819:agonists*; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects; D008297:Male; D008810:Mice, Inbred C57BL; D008823:Micelles; D010069:Oxadiazoles / Q000494:pharmacology*; D012995:Solubility; D013110:Sphingosine / Q000819:agonists / Q000031:analogs & derivatives*; D034421:Sus scrofa; D013876:Thiophenes / Q000494:pharmacology*; D013997:Time Factors; D014867:Water / Q000737:chemistry
chemical_list: D003692:Delayed-Action Preparations; D020100:Hydrogels; D008246:Lysophospholipids; D008823:Micelles; D010069:Oxadiazoles; C503964:SEW2871; D013876:Thiophenes; D014867:Water; C060506:sphingosine 1-phosphate; D019344:Lactic Acid; D005780:Gelatin; D013110:Sphingosine
keywords: Controlled release; Gelatin hydrogel; Macrophage recruitment; S1P agonist; SEW2871