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Devi Kalyan Karumanchi, Jeffrey Benner, Steven Cohen, Yana Skrypai, Alex Thomas, Ajinboye Uwensuyi, Elizabeth R Gaillard; Extended Release of Bevacizumab Through Nanoliposomes for Treating Ocular Angiogenesis. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4102.
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© ARVO (1962-2015); The Authors (2016-present)
To develop a sustained release ocular drug delivery system to improve the release kinetics of Bevacizumab to treat ocular angiogenesis
Fluorescent labeled Bevacizumab (Avastin) was encapsulated in cocktail of different liposomal formulations. The liposomes were examined for hydrodynamic diameter, surface morphology, thermal stability and in vitro release using dynamic light scattering, transmission electron microscopy, differential scanning calorimetry and dissolution studies respectively. Dutch belted rabbits were used as animal models to compare controls with various strategies like liposomal injections, hydrogels and drug depot implants to improve the sustained release of Avastin over a longer period of time. Sustained release and diffusion of the fluorescent labeled antibodies in the rabbit’s eye was screened using a Fluorotron spectrofluorometer on a weekly basis.
The liposomal formulations after extrusion exhibited a narrow size distribution of approximately 100-150 nm in diameter with around 85-92% encapsulation efficiency. From the in vitro drug release studies, we observed a timed release over a period of 6-8 months depending on the composition of the formulation. Through trapping the bevacizumab loaded liposomes in hydrogels and drug depot implants, we were able to extend the release to about 7-8 months in vitro. In vivo drug release kinetics and distribution using Dutch belted rabbits as animal models to test the efficacy of liposomes, hydrogels and the implant are currently in progress.
Liposomal compositions were modified to improve the stability and to extend the time of release. Abrishami et al have been able to obtain a sustained release of the anti-VEGF drugs up to a period of 42 days. We have been successful in encapsulating a model protein into our stable liposomal formulations and employ different intravitreal administration strategies to attain a controlled release over a period of 6-8 months in vitro. Currently, we are studying the in vivo drug release kinetics and distribution using Dutch belted rabbits as animal models. With this study, our efforts would be to decrease the frequency of intravitreal injections from 12 to 2 per year, thereby effectively making the treatment more economical.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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