title: Composite fiber structures with antiproliferative agents exhibit advantageous drug delivery and cell growth inhibition in vitro.
abstract: Composite core/shell fiber structures loaded with the antiproliferative drugs paclitaxel or farnesylthiosalicylate (FTS) were developed and studied. The latter is a specific nontoxic Ras inhibitor with a mild hydrophobic nature, which can also be used for local cancer treatment and stent applications. The fibers were composed of a dense polyglyconate core and a porous drug-loaded poly(D,L-lactic-glycolic acid) shell, prepared using freeze drying of inverted emulsions. Our study focused on the release profile of the antiproliferative drugs from the fibers, the shell morphology and its degradation and erosion. The postfabrication antiproliferative effect of the drugs was tested in a cell culture. The process parameters were found to affect the drug-release profile via two routes: (1) direct, through water uptake and swelling of the structure leading to FTS release, or through degradation of the host polymer leading to paclitaxel release at a later stage; (2) indirect effect of the microstructure on the release profile. The fabrication process did not reduce the pharmacological activity of either paclitaxel or FTS. FTS-eluting composite fibers proved to effectively induce growth inhibition or cell death by a gradient effect and dose-dependent manner. The combined effect of the targeted mechanism of FTS as a Ras inhibitor together with the localized and controlled release characteristics of the fiber is an advantageous antiproliferative quality. It is therefore suggested that our drug-eluting fibers may be used in biomedical applications that require short release (restenosis) or prolonged release (cancer therapy).
authors.affiliation: Faculty of Engineering, Department of Biomedical Engineering, Tel-Aviv University, Tel-Aviv 69978, Israel.
authors.forename: Amir
authors.initials: A
authors.lastname: Kraitzer
authors.forename: Yoel
authors.initials: Y
authors.lastname: Kloog
authors.forename: Roni
authors.initials: R
authors.lastname: Haklai
authors.forename: Meital
authors.initials: M
authors.lastname: Zilberman
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D016503:Drug Delivery Systems; D054855:Drug-Eluting Stents; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D005204:Farnesol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D019344:Lactic Acid / Q000737:chemistry; D017239:Paclitaxel / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry*; D051381:Rats; D012459:Salicylates / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D012995:Solubility; D018631:ras Proteins / Q000037:antagonists & inhibitors
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D004791:Enzyme Inhibitors; D011108:Polymers; D012459:Salicylates; C093323:farnesylthiosalicylic acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D005204:Farnesol; C046409:polyglyconate; D018631:ras Proteins; D017239:Paclitaxel