June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Terminal e-Beam sterilization of Densomeres™ retains structural integrity and sustained bioactivity of bevacizumab in rabbit cornea model
Author Affiliations & Notes
  • Jan S Peterson
    Sustained Nano Systems LLC, Hollywood, Florida, United States
  • WeiLiam Chen
    Sustained Nano Systems LLC, Hollywood, Florida, United States
  • Peter K Kaiser
    Cleveland Clinic Cole Eye Institute, Cleveland, Ohio, United States
  • Barry M. Libin
    Sustained Nano Systems LLC, Hollywood, Florida, United States
  • Jeffrey M Liebmann
    Ophthalmology, Columbia University Irving Medical Center, New York, New York, United States
  • Footnotes
    Commercial Relationships   Jan Peterson Sustained Nano Systems LLC, Code C (Consultant/Contractor); WeiLiam Chen Sustained Nano Systems, EndoMedix, Code O (Owner); Peter Kaiser Sustained Nano Systems LLC, Code C (Consultant/Contractor); Barry Libin Sustained Nano Systems LLC, Code O (Owner); Jeffrey Liebmann Thea, Allergan, Genentech, Code C (Consultant/Contractor), Sustained Nano Systems LLC, Code O (Owner)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 288 – F0091. doi:
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      Jan S Peterson, WeiLiam Chen, Peter K Kaiser, Barry M. Libin, Jeffrey M Liebmann; Terminal e-Beam sterilization of Densomeres™ retains structural integrity and sustained bioactivity of bevacizumab in rabbit cornea model. Invest. Ophthalmol. Vis. Sci. 2022;63(7):288 – F0091.

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

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Abstract

Purpose : Terminal sterilization could reduce production time and costs for anti-angiogenic monoclonal antibodies (mAbs) needed for sustained ocular delivery in retinal diseases if they retain molecular integrity and prolonged in vivo bioactivity. After observing up to 12 months of sustained release and bioactivity in previous in vitro and in vivo tests, highly densified poly(lactic-co-glycolic acid) (PLGA) microspheres (Densomeres™) incorporating bevacizumab were tested again following e-Beam terminal sterilization for their integrity and sustained bioactivity using a rabbit corneal injury model.

Methods : Bevacizumab was incorporated into Densomeres that were resuspended in saline for injection through a 28-ga needle. Control Densomeres contained no active drug. Terminally sterilized doses using e-Beam were assessed for molecular integrity by SEC-HPLC and functional bevacizumab bioactivity in vivo. Six adult male New Zealand white rabbits (3 active, 3 control) were anesthetized and a 9-0 silk suture placed in one cornea of each animal to induce neovascular encroachment from the limbus. A single 0.5 mL subconjunctival injection with Densomeres was made at the same meridian. External photographs taken over 60 days to documented neovascularization were scored on a 0-5 scale by trained observers. If sutures came out during follow-up, they were replaced to maintain the neovascularization stimulus.

Results : Bevacizumab extracted from Densomere samples for SEC-HPLC before and after e-Beam sterilization matched the authentic reference bevacizumab [Fig. 1]. For e-Beam sterilized Densomeres, anti-angiogenic bioactivity persisted after the single injection through Day 60. Comparing controls to eyes receiving Densomeres with bevacizumab, the average difference in scores from Day 7 to Day 60 was 3.2 ± 0.5 [Fig. 2]. This difference matched the sustained effects observed for up to 12 months after a single injection using traditional Densomere preparations.

Conclusions : Compared to controls, e-Beam sterilized Densomeres™ containing the mAb bevacizumab exhibited both structural integrity and prolonged anti-VEGF bioactivity in vivo following a single injection in the rabbit corneal neovascularization model.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

 

SEC-HPLC of bevacizumab from Densomeres™ before and after e-Beam sterilization

SEC-HPLC of bevacizumab from Densomeres™ before and after e-Beam sterilization

 

Rabbit cornea neovascularization scores after a Day 0 suture and single Densomere™ injection

Rabbit cornea neovascularization scores after a Day 0 suture and single Densomere™ injection

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