PRELIMINARY STUDIES IN THE DEVELOPMENTO OF BEVACIZUMAB-LOADED LIPID NANOCAPSULES

PERNOCHI SCERBO, JUAN MATIAS; DANIEL ALBERTO ALLEMANDI; PALMA, SANTIAGO DANIEL; FORMICA, MARÍA LINA

Rosario

Congreso; 7MA REUNIÓN INTERNACIONAL DE CIENCIAS FARMACÉUTICAS; 2023

Corneal neovascularization (NV) involves the formation of new vessels from pre-existing neovascular structures in the avascular cornea, due to a disturbance in the balance between pro- and anti-angiogenic factors. Bevacizumab (BVZ) is a complete recombinant humanized monoclonal antibody of IgG1 isotype (149 kDa) that inhibits the biological activity of all isoforms of human VEGF-A, mainly responsible of NV. Currently, BVZ is used "off-label" for the therapy of proliferative ocular diseases such as NV, however, the need for repeated dosing is associated with an increased risk of corneal epithelial defects. In this work, we propose the development of lipid nanocapsules loaded with bevacizumab with the aim of improving the ocular permeation of BVZ, and optimizing its safety and efficacy. In this regard, we first explored the obtaining of reverse micelles (RM) with different proportions of Labrafac® WL 1349 and Dioctyl Sulfosuccinate Sodium (DSS) by means of different heating and melting procedures of the excipients, followed by the preparation of RM loaded lipid nanocapsules (RM-LNC) Then, preliminary studies were carried out to obtain bevacizumab reverse micelles-loaded lipid nanocapsules (BVZ-RM-LNC), which were obtained by an optimized phase inversion method (PIT). All systems were characterized in terms of average particle size (APS), polydispersity index (PDI) and zeta potential (ZP) by dynamic light scattering (DLS). Acceptable RM with an APS (1-10 nm) were prepared by emulsification under direct heat and co-melting of DSS and Labrafac® WL 1349. and the incorporation of RM into lipid nanocapsules (RM-LNC) showed a size of (64.29±2.08) nm, with a narrow size distribution (PI less than 0.2), and a ZP of (-46.23±7.53) mV. Then, BVZ-RM-LNC presented an APS of (65.87±0.96) nm, a PDI of (0.173±0.082) and a ZP of (-41.1±8.7) mV. In turn, BVZ-RM-LNC showed no significant difference in the parameters studied in relation to RM-LNC. Moreover, APS and PDI remain stable for at least a period of 30 days under storage conditions at 4-8 °C. The obtained formulation could be a promising strategy for the ocular application of BVZ. Future studies of characterization, encapsulation efficiency, antigen affinity and in vitro/in vivo therapeutic efficacy will be carried out.