ChemRN: Bioorganic Chemistry (Topic)最新文献

{"title":"Indented Polymer Microparticles with Shape Variety Reminiscent of Poikilocytosis for Intratumoral Drug Delivery after Transarterial Chemo-Embolization","authors":"A. Benzina, Aigerim Karina, Marion Guillonneau, Samal Tazhibayeva, Haiyan Fan, L. Koole","doi":"10.2139/ssrn.3446992","DOIUrl":"https://doi.org/10.2139/ssrn.3446992","url":null,"abstract":"Transarterial chemo-embolization with drug-eluting embolic beads (DEB-TACE) is rapidly gaining acceptance and importance in interventional oncology, particularly in the treatment of patients with intermediate-stage hepatocellular carcinoma. The technique is still evolving, recent technical developments include the launching of imageable radiopaque drug-eluting particles which consist of crosslinked poly(vinylalcohol) with covalent bonds to sulfonate groups and single-aromatic rings to which 3 (X-absorbing) iodine atoms are attached. Here, we report on conceptually different radiopaque polymeric drug-eluting embolic particles, which are (i), crosslinked poly(methacrylates); (ii), radiopaque since 4-iodobenzoylethyl methacrylate was built-in; (iii), microporous; (iv), having one large indentation to accommodate crystalline drug; (v), able to carry/release lipophilic drugs into/inside the tumor's microvasculature; many effective cytostatics in clinical use fall into this category. We were stunned to find indented microparticles after running a suspension polymerization in the presence of Cu(0). The particles have the same shape-variety that is well-known to exist for erythrocytes (red blood cells), although they are roughly 3000 times larger. This is -to the best of our knowledge- a novum in macromolecular/organic chemistry. Quite old theoretical studies explaining the peculiar shapes of healthy and diseased red blood cells, and recent studies on the catalytic effect of Cu(0) on free-radical polymerizations, provided clues to understand our findings. More importantly, the indented particles were found to be chargeable with lipophilic drugs which cannot be used with normal DEB-TACE formulations, and which are nonetheless crucially important in oncology. This concerns the taxanes (diterpenes) in particular. Hence, we believe that our new indented non-spherical particles hold the promise of becoming scope-widening for DEB-TACE, which is likely to become a cornerstone technique of interventional oncology in the years ahead.","PeriodicalId":321270,"journal":{"name":"ChemRN: Bioorganic Chemistry (Topic)","volume":"30 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121436544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}