ABSTRACT
Purpose
To develop rapamycin-eluting electrospun polyurethane (PU) vascular grafts that could effectively suppress local smooth muscle cell (SMC) proliferation.
Methods
Rapamycin (RM) was incorporated in PU fibers by blend electrospinning using three distinct blending methods. The drug release profiles and the bioavailability of RM-containing PU fibers in the form of fibrous mats and vascular grafts were evaluated up to 77 days in vitro.
Results
RM-contained PU fibers generated by the three distinct blending methods exhibited significantly different fiber diameters (200–500 nm) and distinct RM release kinetics. Young’s moduli of the electrospun fibrous mats increased with higher RM contents and decreased with larger fiber diameters. For all blending methods, RM release kinetics was characteristic of a Fickian diffusion for at least 77 days in vitro. RM-PU fibers generated via powder blending showed the highest encapsulation efficiency. The RM in grafts made of these fibers remained bioactive and was still able to inhibit smooth muscle cell proliferation after 77 days of continual in vitro release.
Conclusions
Electrospun RM-containing PU fibers can serve as effective drug carriers for the local suppression of SMC proliferation and could be used as RM-eluting scaffolds for vascular grafts.
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Abbreviations
- AB:
-
almarBlue
- BSA:
-
bovine serum albumin
- DMEM:
-
Dulbecco’s Modified of Eagle’s Medium
- FBS:
-
fetal bovine serum
- HFP-1:
-
1, 1, 3, 3, 3-Hexafluoro-2-Propanol
- HPLC:
-
high performance liquid chromatography
- NS-IP:
-
normal saline-isopropyl alcohol solution
- PANi:
-
polyaniline
- PBS:
-
phosphate buffered saline
- PGE:
-
PLGA-gelatin-elastin
- PLGA:
-
poly(lactic-co-glycolic acid)
- PTCA:
-
percutaneous transluminal coronary angioplasty
- PU:
-
polyurethane
- RM:
-
rapamycin
- SMC:
-
smooth muscle cell
- SPU:
-
segmented polyurethane
- TCP:
-
tissue culture polystyrene
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ACKNOWLEDGEMENTS AND DISCLOSURES
Jingjia Han and Shady Farah equally contributed to this paper. This work was supported by a translational research grant by HUB (DU/BIOMED-IDR/HUJI) from Drexel University and The Hebrew University of Jerusalem. We thank Dr. Gozde Senel-Ayaz (Drexel BIOMED) for her assistance with SEM and Dr. Wahid Khan (IDR) for his assistance with developing the analytical method used to assess drug release.
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Han, J., Farah, S., Domb, A.J. et al. Electrospun Rapamycin-Eluting Polyurethane Fibers for Vascular Grafts. Pharm Res 30, 1735–1748 (2013). https://doi.org/10.1007/s11095-013-1016-5
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DOI: https://doi.org/10.1007/s11095-013-1016-5