Fatemeh Dadgar Pakdel
1,2 
, Ahmad Mirshahi
3, Payam Zahedi
4, Kazem Mohammad
5, Farkhondeh Hemmati
6, Javad Dadgar Pakdel
7, Mohammad Hossein Nicknam
1,8* , Farid Abedin Dorkoosh
2,9* 1 Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
2 Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
3 Department of Ophthalmology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
4 Department of Polymer, School of Chemical Engineering, College of Engineering, University of Tehran, P. O. Box: 11155-4563, Tehran, Iran.
5 Epidemiology and Biostatistics Department, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
6 Caspian Faculty of Engineering, College of Engineering, University of Tehran, P.O.BOX 43841-119, Gilan, Iran.
7 Department of Pharmaceutical Biotechnology, Pasteur Institute, Tehran, Iran.
8 Molecular Immunology Research Center, Tehran University of Medical Sciences, Tehran, Iran.
9 Medical Biomaterial Research Centre (MBRC), Tehran University of Medical Sciences, Tehran, Iran.
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 (RVO), and diabetic macular edema (DME), 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.