Controlled release of heparin from poly(epsilon-caprolactone) electrospun fibers.
Sustained delivery of heparin to the localized adventitial surface of grafted blood vessels has been shown to prevent the vascular smooth muscle cell (VSMC) proliferation that can lead to graft occlusion and failure. In this study heparin was incorporated into electrospun poly(epsilon-caprolactone) (PCL) fiber mats for assessment as a controlled delivery device. Fibers with smooth surfaces and no bead defects could be spun from polymer solutions with 8%w/v PCL in 7:3 dichloromethane:methanol. A significant decrease in fiber diameter was observed with increasing heparin concentration. Assessment of drug loading, and imaging of fluorescently labeled heparin showed homogenous distribution of heparin throughout the fiber mats. A total of approximately half of the encapsulated heparin was released by diffusional control from the heparin/PCL fibers after 14 days. The fibers did not induce an inflammatory response in macrophage cells in vitro and the released heparin was effective in preventing the proliferation of VSMCs in culture. These results suggest that electrospun PCL fibers are a promising candidate for delivery of heparin to the site of vascular injury.
Luong-Van
Emma
E
School of Molecular and Microbial Sciences, University of Queensland, Brisbane QLD 4072, Australia.
Grøndahl
Lisbeth
L
Chua
Kian Ngiap
KN
Leong
Kam W
KW
Nurcombe
Victor
V
Cool
Simon M
SM
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000633:toxicity; D016503:Drug Delivery Systems; D006493:Heparin / Q000737:chemistry / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D032389:Myocytes, Smooth Muscle / Q000187:drug effects*; D011091:Polyesters / Q000737:chemistry* / Q000633:toxicity; D011817:Rabbits; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D003692:Delayed-Action Preparations; D011091:Polyesters; D014409:Tumor Necrosis Factor-alpha; C016240:polycaprolactone; D006493:Heparin