September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Sustained-release Drug-eluting Microrods as Ocular Implants
Author Affiliations & Notes
  • Anthony Ng
    School of Materials Science & Engineering, Nanyang Technological University, Singapore, Singapore
  • Xu Wen Ng
    School of Materials Science & Engineering, Nanyang Technological University, Singapore, Singapore
  • Yu-Chi Liu
    Singapore Eye Research Institute, Singapore, Singapore
  • Yan Peng
    School of Materials Science & Engineering, Nanyang Technological University, Singapore, Singapore
  • Jodhbir S Mehta
    Singapore Eye Research Institute, Singapore, Singapore
  • Tina T Wong
    Singapore Eye Research Institute, Singapore, Singapore
    School of Materials Science & Engineering, Nanyang Technological University, Singapore, Singapore
  • Subbu Venkatraman
    School of Materials Science & Engineering, Nanyang Technological University, Singapore, Singapore
  • Footnotes
    Commercial Relationships   Anthony Ng, None; Xu Wen Ng, None; Yu-Chi Liu, None; Yan Peng, None; Jodhbir Mehta, None; Tina Wong, None; Subbu Venkatraman, None
  • Footnotes
    Support  Translational and Clinical Research (TCR) Programme NRF NMRC (Singapore)
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 4011. doi:
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    • Get Citation

      Anthony Ng, Xu Wen Ng, Yu-Chi Liu, Yan Peng, Jodhbir S Mehta, Tina T Wong, Subbu Venkatraman; Sustained-release Drug-eluting Microrods as Ocular Implants. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4011.

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

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Abstract

Purpose : The current standard for postoperative anti-inflammation management involves taking eye drops after cataract surgery, and places high emphasis on patient compliance. Our solution is a biodegradable subconjunctival rod shaped implant (microrod) that provides sustained anti-inflammatory drug-release over 4 weeks. Our studies involve in-vitro drug-release and toxicokinetic performance of microrods subconjunctivally implanted in a macaque model.

Methods : The biodegradable copolymer used was poly(L-lactide-co-ε-caprolactone) (PLC). The drug was prednisolone acetate (PA). 40wt% PA microrods were obtained by casting and sectioning into 8mm and 16mm lengths for 2 treatment groups in the macaque study. In-vitro drug-release and mass-loss studies were conducted by immersion of microrods in phosphate-buffered saline and PA and prednisolone content analysed. Twelve female monkeys (Macaca fascicularis) were divided into 2 treatment groups, for both PA-loaded and blank microrods. Six monkeys per group received either 8mm or 16mm microrods, subconjunctivally-implanted in both eyes. The animals were 2 - 4 years, weighing 2 - 4kg. Toxicokinetic (TK) parameter estimation were obtained under GLP-compliance approved by an IACUC committee. Plasma sampling was collected at pre-dose/1h/2h/4h/6h/8h/24h/72h/14 days/4 weeks/13 weeks post-implantation. AUC0-t, Cmax, Tmax and T1/2 were evaluated and descriptive statistics (arithmetic mean, SD, CV%, geometric mean, median, minimum and maximum) were recorded.

Results : Half of 40wt% PA released over a study duration of 6 weeks. Mass loss reached around 18%. This showed that a 40wt% PA content within PLC exhibited sustained-release for about half the study duration. AUC0-t was 45.7% higher and Cmax was 17.2% lower for the animals treated with 40wt% PA 16 mm microrods compared to 8 mm microrods (normalized). There was no significant difference in Tmax, indicating similar PA clearance for single and double dose, and below levels of assumed toxicity. All other findings were not test substance related and showed safety to the microrods.

Conclusions : We have successfully developed a biodegradable subconjunctival microrod that provides sustained anti-inflammatory release. The implanted microrods were not associated with any adverse findings in a macaque model. These positive outcomes, together with efforts to explore office-based microrod delivery, holds much promise for future patients.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

 

Total % PA-release over 6 weeks

Total % PA-release over 6 weeks

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