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Vascular Endothelial Growth Factor-Releasing Microspheres Based on Poly(ε-Caprolactone-PEG-ε-Caprolactone)-b-Poly(L-Lactide) Multiblock Copolymers Incorporated in a Three-Dimensional Printed Poly(Dimethylsiloxane) Cell Macroencapsulation Device.

Authors :
Scheiner KC
Coulter F
Maas-Bakker RF
Ghersi G
Nguyen TT
Steendam R
Duffy GP
Hennink WE
O'Cearbhaill ED
Kok RJ
Source :
Journal of pharmaceutical sciences [J Pharm Sci] 2020 Jan; Vol. 109 (1), pp. 863-870. Date of Electronic Publication: 2019 Oct 22.
Publication Year :
2020

Abstract

Pancreatic islet transplantation is a promising advanced therapy that has been used to treat patients suffering from diabetes type 1. Traditionally, pancreatic islets are infused via the portal vein, which is subsequently intended to engraft in the liver. Severe immunosuppressive treatments are necessary, however, to prevent rejection of the transplanted islets. Novel approaches therefore have focused on encapsulation of the islets in biomaterial implants which can protect the islets and offer an organ-like environment. Vascularization of the device's surface is a prerequisite for the survival and proper functioning of transplanted pancreatic islets. We are pursuing a prevascularization strategy by incorporation of vascular endothelial growth factor (VEGF)-loaded microspheres in 3-dimensional printed poly(dimethylsiloxane)-based devices prior to their prospective loading with transplanted cells. Microspheres (~50 μm) were based on poly(ε-caprolactone-PEG-ε-caprolactone)-b-poly(L-lactide) multiblock copolymers and were loaded with 10 μg VEGF/mg microspheres, and subsequently dispersed in a hyaluronic acid carrier liquid. In vitro release studies at 37°C demonstrated continuous release of fully bioactive VEGF for 4 weeks. In conclusion, our results demonstrate that incorporation of VEGF-releasing microspheres ensures adequate release of VEGF for a time window of 4 weeks, which is attractive in view of the vascularization of artificial pancreas implants.<br /> (Copyright © 2020 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
1520-6017
Volume :
109
Issue :
1
Database :
MEDLINE
Journal :
Journal of pharmaceutical sciences
Publication Type :
Academic Journal
Accession number :
31654660
Full Text :
https://doi.org/10.1016/j.xphs.2019.10.028