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dc.contributor.authorWennink JWH
dc.contributor.authorLiu Y
dc.contributor.authorMäkinen PI
dc.contributor.authorSetaro F
dc.contributor.authorde la Escosura A
dc.contributor.authorBourajjaj M
dc.contributor.authorLappalainen JP
dc.contributor.authorHolappa LP
dc.contributor.authorvan den Dikkenberg JB
dc.contributor.authorAl Fartousi M
dc.contributor.authorTrohopoulos PN
dc.contributor.authorYlä-Herttuala S
dc.contributor.authorTorres T
dc.contributor.authorHennink WE
dc.contributor.authorvan Nostrum CF
dc.date.accessioned2017-07-21T09:40:38Z
dc.date.available2017-07-21T09:40:38Z
dc.date.issued2017
dc.identifier.urihttps://erepo.uef.fi/handle/123456789/3695
dc.description.abstractSelective elimination of macrophages by photodynamic therapy (PDT) is a new and promising therapeutic modality for the reduction of atherosclerotic plaques. m-Tetra(hydroxyphenyl)chlorin (mTHPC, or Temoporfin) may be suitable as photosensitizer for this application, as it is currently used in the clinic for cancer PDT. In the present study, mTHPC was encapsulated in polymeric micelles based on benzyl-poly(ε-caprolactone)-b-methoxy poly(ethylene glycol) (Ben-PCL-mPEG) using a film hydration method, with loading capacity of 17%. Because of higher lipase activity in RAW264.7 macrophages than in C166 endothelial cells, the former cells degraded the polymers faster, resulting in faster photosensitizer release and higher in vitro photocytotoxicity of mTHPC-loaded micelles in those macrophages. However, we observed release of mTHPC from the micelles in 30 min in blood plasma in vitro which explains the observed similar in vivo pharmacokinetics of the mTHPC micellar formulation and free mTHPC. Therefore, we could not translate the beneficial macrophage selectivity from in vitro to in vivo. Nevertheless, we observed accumulation of mTHPC in atherosclerotic lesions of mice aorta's which is probably the result of binding to lipoproteins upon release from the micelles. Therefore, future experiments will be dedicated to increase the stability and thus allow accumulation of intact mTHPC-loaded Ben-PCL-mPEG micelles to macrophages of atherosclerotic lesions.
dc.language.isoEN
dc.relation.ispartofseriesEUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
dc.rightsCC BY http://creativecommons.org/licenses/by/4.0/
dc.titleMacrophage selective photodynamic therapy by meta-tetra(hydroxyphenyl)chlorin loaded polymeric micelles : a possible treatment for cardiovascular diseases
dc.description.versionpublished version
dc.contributor.departmentA.I. Virtanen -instituutti
dc.contributor.departmentA.I. Virtanen -instituutti / Bioteknologia ja molekulaarinen lääketiede
uef.solecris.id48421298
dc.type.publicationinfo:eu-repo/semantics/article
dc.rights.accessrights© Authors
dc.relation.doi10.1016/j.ejps.2017.06.038
dc.description.reviewstatuspeerReviewed
dc.format.pagerange112-125
dc.publisher.countryAlankomaat
dc.relation.issn0928-0987
dc.relation.volume107
dc.rights.accesslevelopenAccess
dc.type.okmA1
dc.type.versioninfo:eu-repo/semantics/publishedVersion
uef.solecris.openaccessHybridijulkaisukanavassa ilmestynyt avoin julkaisu


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