A Novel Approach for Development of Intraocular Biodegradable Ranibizumab Implant: A Solution for Stability of Protein Activity Publisher



Pakdel FD^{1, 2} ; Mirshahi A³ ; Zahedi P⁴ ; Mohammad K⁵ ; Hemmati F⁶ ; Pakdel JD⁷ ; Nicknam MH^{1, 8} ; Dorkoosh FA^{2, 9} Show Affiliations
Source: Advanced Pharmaceutical Bulletin Published:2021

Abstract

Purpose: Ranibizumab is a monoclonal antibody fragment, targeting all isoforms of vascular endothelial growth factor A (VEGF-A), a protein involved in angiogenesis. It is used to treat age-related macular degeneration (AMD), retinal vein occlusion, and diabetic macular edema, which are associated with blindness worldwide. However, proper treatment can decrease the loss of vision in about 90% of patients. Because of poor drug uptake in topical therapy and several adverse side effects of systemic irregularities and intravitreal injections, sustained-release drug delivery systems are more suitable for treatment. However, there are many challenges in the development of these systems due to the loss of protein activities. Methods: After drug complexation by the ion pairing method and preparation of a polymeric implant, containing the drug, the characteristics of the complexes were examined by Fourier-transform infrared spectroscopy and circular dichroism spectroscopy. The stability of antibody activity and biocompatibility of the released drug from the implant were assessed by bioassays and MTT assay, respectively. Finally, the release kinetics were investigated. Results: The bioassays showed the higher activity of the drug complex, compared to the free form, besides good biocompatibility in vitro. Also, the release data confirmed sustained and controlled release characteristics for the prepared implant. Conclusion: In this study, for the first time, we proposed a method for developing a sustained-release intraocular implant, consisting of ranibizumab by the heating method. This method allows for the industrial production of ranibizumab by extrusion and eliminates the complications related to reservoir systems. © 2021 The Author (s). This is an Open Access article distributed under the terms of the Creative Commons Attribution (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, as long as the original authors and source are cited. No permission is required from the authors or the publishers.