A New Bevacizumab Carrier for Intravitreal Administration: Focus on Stability

• Main Authors: Daniela Chirio, Elena Peira, Simona Sapino, Giulia Chindamo, Simonetta Oliaro-Bosso, Salvatore Adinolfi, Chiara Dianzani, Francesca Baratta, Marina Gallarate
• Format: Article
• Language: English
• Published: MDPI AG 2021-04-01
• Series: Pharmaceutics
• Subjects: lipid nanoparticles; microemulsion; bevacizumab; structure stability; biocompatibility; intravitreal injection
• Online Access: https://www.mdpi.com/1999-4923/13/4/560

Bevacizumab (BVZ) is a monoclonal antibody that binds to human vascular endothelial growth factor A (VEGF-A) and inhibits the interaction between VEGF-A and VEGF receptors, thus blocking the angiogenesis. Repeated intravitreal injections of BVZ for the treatment of ocular pathologies that present an excessive proliferation results in a low patience compliance. BVZ is specially indicated for the treatment of diabetic and degenerative retinopathy. In the present study, we designed lipid nanoparticles (NPs) as a BVZ sustained drug delivery system for reducing the frequency of administration. We used a simple and highly efficient procedure, “Cold dilution of microemulsions”, to obtain spherical NPs with mean diameters of 280–430 nm, Zeta potentials between −17 and −31 mV, and drug entrapment efficiencies between 50 to 90%. This study focused on the biochemical and biophysical stabilities of BVZ after entrapment in NPs. SDS-PAGE electrophoretic analysis and circular dichroism, dynamic light scattering, and scanning electron microscopy were used to characterize BVZ-loaded NPs. The biocompatibility was assessed by in vitro cell compatibility studies using the ARPE-19 cell line. Thus, in this work, a stable BVZ-loaded system was obtained. In addition, several studies have shown that BVZ is released slowly from the lipid matrix and that this system is biocompatible. The results are promising and the developed NPs could be exploited to create a new, potentially effective and minimally invasive treatment of intraocular diseases.