Nanoparticles as drug carriers in the treatment of corneal neovascularization

INES LUIS REDIN; M. AGÜEROS; J. LLABOT; ALLEMANDI D; IRACHE J. M

Pamplona

Simposio; 19th International symposium on microencapsulation; 2013

Nanoparticles as drug carriers in the treatment of corneal neovascularization Inés Luis-Redín, M. Agüeros, J.M. Llabot, D. Allemandi, J. M. Irache Corneal neovascularization is a serious condition that can lead to a significant decline in vision. In individuals suffering from this disease, there is a generation of abnormal vessels that block light, cause corneal scarring, compromise visual acuity, and may lead to inflammation and edema. All of this would be consequence of the up-regulation of the synthesis of angiogenic factors (i.e. VEGF or vascular endothelial growth factor). Corneal neovascularization may also occur secondary to chemical burns, ischemia, infection, trauma, and inflammation, and is a major cause of blindness that affects up to 4.14% of patients being treated for eye care or approximately 1.4 million people per year [1]. Current treatments for corneal NV include steroid or non-steroidal anti-inflammatory agents, laser photocoagulation, fine-needle diathermy, photodynamic therapy, and anti-VEGF agents (i.e. bevacizumab). In this way, different studies have demonstrated that topical bevacizumab can reduce corneal neovascularization in humans [2]. More recently, the combination of suramin and bevacizumab (Suramab) has shown to have a synergistic effect, characterized by a therapeutic success in a rabbit model after intravenous administration [3]. Another possible strategy would be the use of nanoparticles capable of developing adhesive interactions with the eye surface in order to prolong the time in close contact with the mucosal surface, thus permitting a sustained and prolonged release of the therapeutic agents. In this context, in a first approach, the aim of this work was the preparation and characterization of poly(anhydride) nanoparticles loaded with either suramin or bevacizumab. Nanoparticles loaded with either suramin or bevacizumab were prepared from the incubation of the drug with the copolymer of methyl vinyl ether and maleic anhydride (Gantrez AN) in acetone. Then nanoparticles were formed by the addition of a mixture of ethanol and water, purified and freeze-dried. On one hand, suramin-loaded nanoparticles displayed a size of about 380 nm and a negative surface charge (zeta potential of ? 50mV) with a drug loading of 80 μg suramin per mg nanoparticles. On the other hand, bevacizumab-loaded nanoparticles showed a mean size of 250 nm, a zeta potential of -45 mV and a drug loading close to 100 μg bevacizumab per mg nanoparticles. In summary, poly(anhydride) nanoparticles are useful to encapsulate both suramin or bevacizumab. The next steps will be devoted to the co-encapsulation of both compounds in these poly(anhydride) nanoparticles as well as their in-vitro and in-vivo evaluation. References 1. Bachmann B, Bock F, Wiegand S, et al. Promotion of graft survival by vascular endothelial growth factor a neutralization after high-risk corneal transplantation. Arch Ophthalmol 126:71-7 (2008) 2. Dastjerdi M, Al-Arfaj K, Nallasamy N, et al. Topical bevacizumab in the treatment of corneal neovascularization: results of a prospective, open-label, non-comparative study. Arch Ophthalmol 127: 381-9 (2009) 3. Lopez ES, Rizzo MM, Croxatto JO, et al. Suramab, a novel antiangiogenic agent, reduces tumor growth and corneal neovascularization. Cancer Chem Pharmacol 67:723-8 (2011). Acknowledgements This research project is funded by the Spanish Ministry of Innovation and Science (ref. PRI-PIBAR-2011-1377).