April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Development of Precisely-Engineered Biodegradable Drug Delivery Systems for Posterior Ocular Drug Delivery: PRINT® PLGA Extended Release Implants for anti-VEGF Biologics
Author Affiliations & Notes
  • Benjamin Maynor
    Envisia Therapeutics, Research Triangle Park, NC
  • Andres Garcia
    Envisia Therapeutics, Research Triangle Park, NC
  • Janet Tully
    Envisia Therapeutics, Research Triangle Park, NC
  • Gary Owens
    Envisia Therapeutics, Research Triangle Park, NC
  • RiLee Robeson
    Envisia Therapeutics, Research Triangle Park, NC
  • Tomas Navratil
    Envisia Therapeutics, Research Triangle Park, NC
  • Brian C Gilger
    North Carolina State University, Raleigh, NC
  • Benjamin R Yerxa
    Envisia Therapeutics, Research Triangle Park, NC
  • Footnotes
    Commercial Relationships Benjamin Maynor, Envisia Therapeutics (E); Andres Garcia, Envisia Therapeutics (E); Janet Tully, Envisia Therapeutics (C); Gary Owens, Envisia Therapeutics (E); RiLee Robeson, Envisia Therapeutics (E); Tomas Navratil, Envisia Therapeutics (E); Brian Gilger, Envisia Therapeutics (C); Benjamin Yerxa, Envisia Therapeutics (E)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 5269. doi:https://doi.org/
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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. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract
 
Purpose
 

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.

 
Methods
 

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.

 
Results
 

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.

 
Conclusions
 

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.

  
Keywords: 700 retinal neovascularization • 608 nanomedicine • 748 vascular endothelial growth factor  
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