VEGF-functionalized dextran has longer intracellular bioactivity than VEGF in endothelial cells.

Herein, we report that VEGF-functionalized dextran (dexOx-VEGF) is comparatively superior to free VEGF in prolonging the phosphorylation of VEGF receptor 2 (VEGFR-2). Both dexOx-VEGF and free VEGF activate VEGFR-2, and the complexes are internalized into early endosomes (EEA1(+) vesicles) and then transported to lysosomes (Rab7(+) vesicles). However, after cell activation, dexOx-VEGF is preferentially colocalized in early endosomes where VEGF signaling is still active while free VEGF is preferentially transported to late endosomes or lysosomes. We further show that dexOx-VEGF after phosphorylation of VEGF receptor 2 induces an increase of intracellular Ca(2+) and activates VEGF downstream effectors such as Akt and extracellular signal-regulated kinase (ERK1/2) proteins. Under specific conditions, the activation level is different from the one observed for free VEGF, thus suggesting mechanistic differences, which is illustrated by cell migration and cord-like formation studies. DexOx-VEGF can be cross-linked with adipic acid dihydrazide to form a degradable gel, which in turn can be incorporated in a fibrin gel containing endothelial cells (ECs) to modulate their activity. We envision that these constructs might be beneficial to extend the pro-angiogenic activity of VEGF in ischemic tissues and to modulate the biological activity of vascular cells.

Drug delivery systems: Advanced technologies potentially applicable in personalized treatments.

Advanced drug delivery systems (DDS) present indubitable benefits for drug administration. Over the past three decades, new approaches have been suggested for the development of novel carriers for drug delivery. In this review, we describe general concepts and emerging research in this field based on multidisciplinary approaches aimed at creating personalized treatment for a broad range of highly prevalent diseases (e.g., cancer and diabetes). This review is composed of two parts. The first part provides an overview on currently available drug delivery technologies including a brief history on the development of these systems and some of the research strategies applied. The second part provides information about the most advanced drug delivery devices using stimuli-responsive polymers. Their synthesis using controlled-living radical polymerization strategy is described. In a near future it is predictable the appearance of new effective tailor-made DDS, resulting from knowledge of different interdisciplinary sciences, in a perspective of creating personalized medical solutions.

Immobilisation of cardosin A in chitosan sponges as a novel implant for drug delivery.

Cardosin A is extracted from the pistils of the plant Cynara cardunculus L. and chitosan is a polysaccharide derived from chitin with valuable properties as a biomaterial. In this work we report our experiments on the synthesis of chitosan sponges and immobilisation of cardosin A, by entrapment. We observed that 10-15% of the incorporated cardosin A were released over 6 days of incubation. In addition, we could also note that this immobilisation procedure did not induce any specificity alterations on cardosin A. The specificity study of the enzyme, using beta-chain of oxidised insulin, showed that the immobilised and released enzymes have the same hydrolysis pattern as the free enzyme. The ability of this enzyme to hydrolyse type I collagen was maintained, after the immobilisation procedure. The biocompatibility in vivo of these sponges was evaluated by histological staining after implantation in rats submitted to abdominal surgery. Results of this study demonstrated that these chitosan sponges are very promising vehicles for the application of cardosin A, in abdominal cavity for prevention and reduction of the adhesions formation.