Taha Hammady

Publications (2)6.21 Total impact

• Article: Functionalized nanospheres loaded with anti-angiogenic drugs: cellular uptake and angiosuppressive efficacy.

  Taha Hammady, Jean-Michel Rabanel, Renu Singh Dhanikula, Grégoire Leclair, Patrice Hildgen
  [show abstract] [hide abstract]
  ABSTRACT: The objective of this study was to develop polymeric nanospheres (NPs) that are able to selectively target the activated vascular endothelium and to deliver co-encapsulated anti-angiogenic agents for improved treatment efficacy in inflammatory diseases with an angiogenic component. We evaluated a novel poly(d,l)-lactide (PLA)-based polymer, grafted with a synthetic ligand specific for selectin (PLA-g-SEL), for the preparation of functionalized NPs. The NPs were produced according to a double emulsion-solvent diffusion/evaporation method, allowing the co-encapsulation of hydrophilic and lipophilic drugs. Incorporation of the functionalized polymer enhanced the internalization of fluorescein-labeled NPs by lipopolysaccharide-activated vascular endothelial cells relative to control NPs, as evidenced by confocal laser scanning microscopy and quantitative fluorescence measurements. Two anti-angiogenic agents, endostatin and paclitaxel, were co-loaded in the functionalized NPs. Respective drug loadings were optimized by adjusting polymer composition, as well as by the microemulsion technique. NPs loaded with either of the chosen drugs or with a combination of them were tested for their anti-angiogenic efficacy in human umbilical vascular endothelial cell (HUVEC) culture in vitro and rat aorta tissue culture ex vivo models. An enhanced anti-proliferative effect on HUVECs and heightened anti-angiogenic action on rat aorta ring cultures was observed for the loaded drugs compared to the free molecules. Moreover, combined loaded treatments were found to be more potent, evoking additive and even synergetic outcomes (at lower doses) greater than the corresponding single-loaded treatments in inhibiting new vessels sprouting in rat aortic rings.
  European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 07/2009; 72(2):418-27. · 3.15 Impact Factor
• Article: On the mechanism and dynamics of uptake and permeation of polyether-copolyester dendrimers across an in vitro blood-brain barrier model.

  Renu Singh Dhanikula, Taha Hammady, Patrice Hildgen
  [show abstract] [hide abstract]
  ABSTRACT: Dendrimers have emerged as a promising drug delivery system due to their well defined size, tailorability, and multifunctional nature. However, their application in brain delivery is relatively a new area of research. The present study was aimed at evaluating the uptake and permeation of polyether-copolyester (PEPE) dendrimers across the blood-brain barrier model and exploring the underlying mechanisms. Saturation was observed in the uptake of rhodamine B labeled PEPE dendrimers by brain vascular endothelial (bEnd.3) cells at high concentrations. Clathrin and caveolin inhibitors produced partial inhibition of the dendrimer uptake, signifying contribution of both pathways in the uptake process. PEPE dendrimers were able to cross in vitro BBB model in high amounts with P(app) of 19.7 +/- 1.9 x 10(-6) cm/s and 38.6 +/- 4.1 x 10(-6) cm/s for den-1-(G2)-400 and den-2-(G2)-400, respectively; and only 11-14% reduction in transendothelial electrical resistance during initial 4 h. The results of this study suggest that architecture of dendrimers plays a major role not only in influencing the extent and mechanism of uptake by bEnd.3 cells but also permeation across the BBB model. =
  Journal of Pharmaceutical Sciences 02/2009; 98(10):3748-60. · 3.06 Impact Factor