Nanoparticles as carriers of suramin in the treatment of corneal neovascularization

INES LUIS REDIN; AGÜEROS M.; LLABOT, J.; BOIERO C; IRACHE J. M

Dresden

Congreso; Crossing Biological Barriers ? Advances in Nanocarrier Design for Targeted Drug Delivery; 2015

Corneal neovascularization (CNV) is characterized by the formation of new vascular structures in areas that were previously avascular. The abnormal vessels block light, cause corneal scarring, compromise visual acuity, and may lead to inflammation and edema. Recently, the association between suramin and bevacizumab (Suramab?) has demonstrated a higher and more prolonged antiangiogenic effect than the antibody alone or other conventional treatments [1]. In this context, the aim of this work was to develop and optimize nanocarriers based on human serum albumin (HSA) for the topical eye delivery of suramin.HSA nanoparticles were prepared by a desolvationprocedure using ethanol, stabilized by addition of either glutaraldehyde (Nps-Glu) or Gantrez ES-425? (Nps-Ga), purified and finally dried by lyophilization. For suramin-loaded nanoparticles (S-Nps-Ga or S-Nps-Glu), the drug was added to the albumin solutionand the nanocarriers were preparedin the same way as described above.For empty nanoparticles, the size of nanoparticles stabilized by incubation with Gantrez was found to be higher than those cross-linked with glutaraldehyde (210 vs 160 nm). However, in both cases, the resulting nanocarriers were homogeneous and negatively charged (between -35 and -39 mV). On the other hand, for suramin-loaded nanoparticles, the physico-chemical characteristics of S-Nps-Glu were quite similar to those observed for S-Nps-Ga. Their mean size was approximately 200 nm and the drug loading was calculated to be close to 120 μg/mg nanoparticle. Regarding in vitro release kinetics, the release of suramin from nanoparticles stabilized by coating with Gantrez was faster than that from nanoparticles cross-linked with glutaraldehyde. After 8 h of incubation in PBS, 70% of suramin was released from S-NPs-Ga and only 50% from S-Nps-Glu.In summary, Gantrez® ES-425 may be an appropriate stabilizing agent for HSA nanoparticles, avoiding the drawbacks associated with the use ofglutaraldehyde. References[1] Lopez et al. (2011). Cancer. Chemother. Pharmacol. 67, 723-728.AcknowledgementsThis research has received funding from the ?Ministerio de Ciencia e Innovación" (PRI-PIBAR-2011-1377) in Spain and CONICET and FONCyT (BID 2473/OC-AR PICT 2010-0380) in Argentina.