title: Biocatalytic polymer coatings: on-demand drug synthesis and localized therapeutic effect under dynamic cell culture conditions.
abstract: Biocatalytic surface coatings are prepared herein for localized synthesis of drugs and their on-demand, site-specific delivery to adhering cells. This novel approach is based on the incorporation of an enzyme into multilayered polymer coatings to accomplish enzyme-prodrug therapy (EPT). The build-up of enzyme-containing multilayered coatings is characterized and correlations are drawn between the multilayer film assembly conditions and the enzymatic activity of the resulting coatings. Therapeutic effect elicited by the substrate mediated EPT (SMEPT) strategy is investigated using a prodrug for an anticancer agent, SN-38. The performance of biocatalytic coatings under flow conditions is investigated and it is demonstrated that EPT allows synthesizing the drugs on-demand, at the time desired and in a controllable amount to suit particular applications. Finally, using cells cultured in sequentially connected flow chambers, it is demonstrated that SMEPT affords a site-specific drug delivery, that is, exerts a higher therapeutic effect in cells adhering directly to the biocatalytic coatings than in the cells cultured "downstream". Taken together, these data illustrate biomedical opportunities made possible by engineering tools of EPT into multilayered polymer coatings and present a novel, highly versatile tool for surface mediated drug delivery.
authors.affiliation: Department of Chemistry, Aarhus University, Aarhus, 8000, Denmark.
authors.forename: Betina
authors.initials: B
authors.lastname: Fejerskov
authors.forename: Najah B S
authors.initials: NB
authors.lastname: Jensen
authors.forename: Boon M
authors.initials: BM
authors.lastname: Teo
authors.forename: Brigitte
authors.initials: B
authors.lastname: Städler
authors.forename: Alexander N
authors.initials: AN
authors.lastname: Zelikin
mesh_terms: D055162:Biocatalysis; D002166:Camptothecin / Q000031:analogs & derivatives / Q000494:pharmacology; D018929:Cell Culture Techniques / Q000379:methods*; D002470:Cell Survival / Q000187:drug effects; D020099:Coated Materials, Biocompatible / Q000494:pharmacology*; D005966:Glucuronidase / Q000378:metabolism; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D000077146:Irinotecan; D010477:Perfusion; D004364:Pharmaceutical Preparations / Q000138:chemical synthesis*; D011108:Polymers / Q000494:pharmacology*; D011355:Prodrugs / Q000138:chemical synthesis; D058525:Quartz Crystal Microbalance Techniques
chemical_list: D020099:Coated Materials, Biocompatible; D004364:Pharmaceutical Preparations; D011108:Polymers; D011355:Prodrugs; D000077146:Irinotecan; D005966:Glucuronidase; D002166:Camptothecin
keywords: Biomaterials; Enzyme - prodrug therapy; Multilayered polymer coatings; Shear stress; Surface mediated drug delivery