Synthesis of RGD Analogs as Potential Vectors for Targeted Drug Delivery

Promoting regeneration of peripheral nerves in-vivo using new PCL-NGF/Tirofiban nerve conduits

“…The enhancement of PCL-NGF scaffolds of on the growth of PC12 cells in this study could be due to the interactions of NGF and Trk A receptors on the membrane of PC12 cells [16e18]. Furthermore, the rate of cellular uptake of RGD-modified polymeric micelles by PC12 cells was enhanced compared to that of micelles without modification [12,13]. Since TF has the same functions as RGD integrin, the promotion by TF on the growth of PC12 cells in PCL-NGF/TF scaffolds was also demonstrated (Fig.…”

“…Tirofiban (TF) is a non-peptide RGD-mimetic molecule [10] that is produced from the snake venom, echistatin and has a function that is analogous to that of arginine-glycine-aspartic acid (RGD), a wellknown minimal cell-recognizable peptide of numerous adhesive plasma and extracellular proteins such as fibronectin [7,10,11]. Functionally, TF is extensively employed as a clinical anti-thrombosis drug to block the receptors of glycoprotein (GP) IIb/IIIa on the membrane of human platelets and thereby inhibit platelet aggregation [11,12]. The binding of ligands to integrins is well known to produce intracellular signals and regulate cellular growth and differentiation [12].…”

“…Functionally, TF is extensively employed as a clinical anti-thrombosis drug to block the receptors of glycoprotein (GP) IIb/IIIa on the membrane of human platelets and thereby inhibit platelet aggregation [11,12]. The binding of ligands to integrins is well known to produce intracellular signals and regulate cellular growth and differentiation [12]. For instance, RGD peptide has been employed to promote the growth of various cells on different biomaterials such as PCL [7].…”

“…For instance, RGD peptide has been employed to promote the growth of various cells on different biomaterials such as PCL [7]. Furthermore, for using as drug delivery carriers, the rate of cellular uptake of RGD-modified polymeric micelles by neuron-like PC12 cells was enhanced [12,13]. Since TF has similar functions to those of RGD, it may exhibit specific interactions with PC12 cells and is therefore used as one of the constituents of modified PCL scaffolds, to enable its effects on the growth of PC12 cells to be evaluated.…”

“…Since TF molecules have similar functions to those of RGD which may have specific interactions with PC12 cells [12,13], and since NGF may promote the growth of neural-like PC12 cells [8,19], they may have cooperatively effects on promoting the growths of PC12 cells. Accordingly, TF and NGF were grafted onto PCL scaffolds (PCL-NGF/TF) that were coated with a thin layer of chitosan, a polymer that provides amine groups, using a photochemical technique [13,16] for testing the hypothesis.…”