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J Pharm Sci ; 109(1): 863-870, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31654660

RESUMO

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.


Assuntos
Indutores da Angiogênese/química , Dimetilpolisiloxanos/química , Portadores de Fármacos , Poliésteres/química , Polietilenoglicóis/química , Impressão Tridimensional , Fator A de Crescimento do Endotélio Vascular/química , Indutores da Angiogênese/farmacologia , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Composição de Medicamentos , Implantes de Medicamento , Liberação Controlada de Fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Ácido Hialurônico/química , Microesferas , Fatores de Tempo , Fator A de Crescimento do Endotélio Vascular/farmacologia
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