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Electrospun Rapamycin-Eluting Polyurethane Fibers for Vascular Grafts

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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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Authors and Affiliations

  1. School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, Pennsylvania, 19104, USA

    Jingjia Han & Peter I. Lelkes

  2. School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, 91120, Israel

    Shady Farah

  3. School of Pharmacy, Faculty of Medicine Center for Nanosciences and Nanotechnology Grass Center for Drug Design and Synthesis, The Hebrew University of Jerusalem, Jerusalem, 91120, Israel

    Abraham J. Domb

  4. Department of Bioengineering, College of Engineering, Temple University, Philadelphia, Pennsylvania, 19122, USA

    Peter I. Lelkes

Authors
  1. Jingjia Han
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  2. Shady Farah
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  3. Abraham J. Domb
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  4. Peter I. Lelkes
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Corresponding authors

Correspondence to Abraham J. Domb or Peter I. Lelkes.

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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

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