April 2014
Volume 55, Issue 13
ARVO Annual Meeting Abstract  |   April 2014
Ovalbumin as a model protein for ranibizumab in a poly(lactic-co-glycolic) acid microsphere drug delivery system
Author Affiliations & Notes
  • Christian R Osswald
    Biomedical Engineering, Illinois Institute of Technology, Chicago, IL
  • Jennifer J Kang Mieler
    Biomedical Engineering, Illinois Institute of Technology, Chicago, IL
  • Footnotes
    Commercial Relationships Christian Osswald, None; Jennifer Kang Mieler, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 464. doi:
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      Christian R Osswald, Jennifer J Kang Mieler; Ovalbumin as a model protein for ranibizumab in a poly(lactic-co-glycolic) acid microsphere drug delivery system. Invest. Ophthalmol. Vis. Sci. 2014;55(13):464.

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

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Purpose: To characterize the release of ovalbumin (OVA) from a poly(lactic-co-glycolic) acid (PLGA) microsphere ocular drug delivery system capable of controlled release for several months. OVA (44.3 kDa), rather than bovine serum albumin (BSA, 66.5 kDa), may better model the release of ranibizumab (48.4 kDa) due to similar molecular weights.

Methods: OVA was radiolabeled with iodine-125 before incorporation into PLGA microspheres. Effects of fabrication techniques and polymer formulation were explored. Protocol A (PLGA 50:50) and Protocol B (PLGA 75:25) used 10% polyvinyl alcohol (PVA) in the outer aqueous phase (w2) and 0.2% PVA during solvent evaporation; Protocol C (PLGA 50:50) used 1% PVA in w2 and 2% isopropanol. Release profiles were measured at 37°C under mild agitation with samples collected at 3, 7, 24, 48, 96, and 168 hours and then weekly. Cumulative release was calculated as a percent of encapsulated drug. Encapsulation efficiency (EE) was defined as the percent-drug within the microspheres relative to initial loading. Initial burst (IB) was defined as drug released within the first 24 hours. Using the same three protocols, BSA microspheres were characterized using the BCA assay. Both OVA and BSA microspheres were sized using a confocal microscope.

Results: Average microsphere diameters were ~10μm (A: 8.4μm±4.3μm; B: 7.7μm±5μm; C: 6μm±3.5μm) with no significant difference between OVA and BSA microspheres. EE was significantly higher in OVA vs BSA microspheres (A: 33.5%±4.4% vs 22.3%±5%; B: 21.8%±3.9% vs 14.1%±2.7%; C: 11.9%±2.6% vs 6.3%±3%). Protocols A and B had significantly reduced IB in OVA vs BSA microspheres (A: 18%±3.3% vs 47.1%±8.2%; B: 20.2%±0.01% vs 25%±4.5%); in Protocol C, IB increased (44.2%±11.5% vs 33.8%±8.6%). For OVA microspheres, both Protocols A and B released beyond 70 days and Protocol C released for over 50 days. BSA microspheres released for 98, 112, and 77 days, respectively. After the IB, OVA microspheres released with t1/2 kinetics, whereas BSA microspheres released ≥80% during the first week.

Conclusions: OVA microspheres showed more desirable characteristics (e.g., higher EE, lower IB, and t1/2 kinetics) than BSA microspheres. While BSA released for significantly longer than OVA, less BSA was released overall. OVA is similar in size to ranibizumab and may be a better model protein for investigating extended-release ocular drug delivery systems.

Keywords: 607 nanotechnology • 608 nanomedicine  

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