Antiangiogenic activity of PLGA-Lupeol implants for potential intravitreal applications

Publication date: August 2017
Source:Biomedicine & Pharmacotherapy, Volume 92
Author(s): Daniel Crístian Ferreira Soares, Diogo Coelho de Paula Oliveira, Luciola Silva Barcelos, Alan Sales Barbosa, Lorena Carla Vieira, Danyelle M. Townsend, Domenico Rubello, André Luis Branco de Barros, Lucienir Pains Duarte, Armando Silva-Cunha
Uncontrolled angiogenesis is directly associated with ocular diseases such as macular degeneration and diabetic retinopathy. Implantable polymeric drug delivery systems have been proposed for intravitreal applications and in the present work, we evaluated the antiangiogenic potential of PLGA ocular implants loaded with the triterpene lupeol using in vitro and in vivo models. The drug/polymer physiochemical properties of the lupeol-loaded PLGA were validated as functionally similar using differential scanning calorimetry, Fourier transform infrared spectroscopy, and scanning electron microscopy. Interestingly, in an in vitro culture system, lupeol (100μg/mL and 250μg/mL) was capable to inhibited the proliferation as well as the migration of Human Umbilical Vein Endothelial Cells (HUVEC), without interfering in cell viability, promoting a significant reduction in the percentage of vessels (39.41% and 44.12%, respectively), compared with the control group. In vivo test, by using the chorioallantoic membrane (CAM) model, lupeol-loaded PLGA ocular implants showed antiangiogenic activity comparable to the FDA-approved anti-VEGF antibody Bevacizumab. Overall, our results suggest lupeol-loaded PLGA ocular implants were able to inhibit the angiogenic process by impairing both proliferation and migration of endothelial cells.

Graphical abstract

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