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Benjamin Maynor, Andres Garcia, Janet Tully, Gary Owens, RiLee Robeson, Tomas Navratil, Brian C Gilger, Benjamin R Yerxa; Development of Precisely-Engineered Biodegradable Drug Delivery Systems for Posterior Ocular Drug Delivery: PRINT® PLGA Extended Release Implants for anti-VEGF Biologics. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5269.
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The ability to precisely manufacture poly(lactic acid-co-glycolic acid) (PLGA) drug delivery systems for biological molecules, such as monoclonal antibodies, antibody fragments, and other biologics has been limited by available technologies (e.g. hot melt extrusion, in-situ gelation, solvent/antisolvent precipitation, microemulsion methods). Here, we present PRINT technology as an alternative technology for fabrication of extended release, biodegradable PLGA implants with precise dose/size/shape uniformity and good retention of biological activity of the active pharmaceutical ingredients, with potential for >2 month extended release of biologics.
We use a low-temperature, solvent-free process to formulate bevacizumab into PLGA intraocular implants to achieve extended release of the active. Solid particles of the active were uniformly dispersed in PLGA matrices and molded to produce size- and shape-controlled implantable drug delivery systems. The implants may contain other protective excipients to improve release kinetics and/or enhance stability of the cargo. In vitro release of biologics from the implants were measured in physiologically relevant media at 37°C and bevacizumab concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Safety, tolerability, and release were monitored in vivo.
PLGA implants containing biologics, including bevacizumab, were successfully fabricated using the PRINT technology (Figure 1A). Bevacizumab loading in implants was 57 μg ±7 μg. Biological activity of bevacizumab was maintained throughout formulation steps and extended release of active bevacizumab over several weeks was confirmed by ELISA (Figure 1B). It was found that protective excipients can enhance the stability of the biologic cargo during implant fabrication.
The PRINT technology allows for the fabrication of drug delivery systems for the extended release of biologics. PRINT offers advantages with respect to formulation of biologics, including low-temperature processing, solvent-free processing, and utilization of protective excipients.
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