Evaluation of a Sustained-release Prednisolone Acetate Biodegradable Subconjunctival Implant in a Non-Human Primate Model
Purpose: We evaluate the toxicity and plasma toxicokinetic (TK) profile of a biodegradable subconjunctival microrod for sustained prednisolone acetate (PA) release over 12 weeks in a non-human primate model. Methods: The biodegradable copolymer poly(l-lactide-co-ε-caprolactone) (PLC) and 40-wt% PA m...
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sg-ntu-dr.10356-882052023-07-14T15:45:51Z Evaluation of a Sustained-release Prednisolone Acetate Biodegradable Subconjunctival Implant in a Non-Human Primate Model Liu, Yu-Chi Ng, Anthony Herr Cheun Ng, Xu Wen Yan, Peng Venkatraman, Subbu Subramanian Mehta, Jodhbir Singh Wong, Tina Tzee Ling School of Materials Science & Engineering Drug Delivery Subconjunctival Purpose: We evaluate the toxicity and plasma toxicokinetic (TK) profile of a biodegradable subconjunctival microrod for sustained prednisolone acetate (PA) release over 12 weeks in a non-human primate model. Methods: The biodegradable copolymer poly(l-lactide-co-ε-caprolactone) (PLC) and 40-wt% PA microrods were used and fashioned into 8 and 16 mm lengths. Twelve monkeys were divided into two treatment groups of PA-loaded and blank microrods, with six monkeys each receiving either 8- or 16-mm microrods subconjunctively implanted into both eyes. TK and hematology parameters were analyzed. Ophthalmic clinical evaluation, including slit-lamp and ophthalmoscopy examinations, was performed. Results: Over the study period of 12 weeks, the mean area under the plasma concentration-time curve was 45.7% higher, and the maximum plasma concentration was 17.2% lower for the animals treated with 40-wt% PA 16-mm microrods compared to 8-mm microrods (251.44 versus 172.54 hours × nanograms per milliliter and 8.53 versus 10.30 ng/mL, respectively). The PA release was significantly below the levels of assumed toxicity. There was no significant difference in the time to reach maximum concentration between the 8- and 16-mm microrod groups (7.33 and 8 hours; P = 0.421). Findings from clinical evaluation, hematology, and histopathology showed no ocular side effects and no significant adverse systemic effects. Conclusion: The PA biodegradable microrods demonstrated safe toxicokinetics even with the larger size implant containing a higher amount of drug. The PA implant may be considered as a safe alternative to the application of topical PA eyedrops. Translational Relevance: The results provide the evidence of the safety of implanting a steroid delivery system subconjunctively, offering an alternative to topical PA eyedrops. NMRC (Natl Medical Research Council, S’pore) MOH (Min. of Health, S’pore) Published version 2018-03-16T07:04:34Z 2019-12-06T16:58:15Z 2018-03-16T07:04:34Z 2019-12-06T16:58:15Z 2017 2017 Journal Article Liu, Y.-C., Ng, A. H. C., Ng, X. W., Yan, P., Venkatraman, S. S., Mehta, J. S., et al. (2017). Evaluation of a Sustained-Release Prednisolone Acetate Biodegradable Subconjunctival Implant in a Non-Human Primate Model. Translational Vision Science & Technology, 6(5), 9-. https://hdl.handle.net/10356/88205 http://hdl.handle.net/10220/44578 10.1167/tvst.6.5.9 203630 en Translational Vision Science & Technology © 2017 The Authors. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. 7 p. application/pdf |
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Drug Delivery Subconjunctival Liu, Yu-Chi Ng, Anthony Herr Cheun Ng, Xu Wen Yan, Peng Venkatraman, Subbu Subramanian Mehta, Jodhbir Singh Wong, Tina Tzee Ling Evaluation of a Sustained-release Prednisolone Acetate Biodegradable Subconjunctival Implant in a Non-Human Primate Model |
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Purpose: We evaluate the toxicity and plasma toxicokinetic (TK) profile of a biodegradable subconjunctival microrod for sustained prednisolone acetate (PA) release over 12 weeks in a non-human primate model. Methods: The biodegradable copolymer poly(l-lactide-co-ε-caprolactone) (PLC) and 40-wt% PA microrods were used and fashioned into 8 and 16 mm lengths. Twelve monkeys were divided into two treatment groups of PA-loaded and blank microrods, with six monkeys each receiving either 8- or 16-mm microrods subconjunctively implanted into both eyes. TK and hematology parameters were analyzed. Ophthalmic clinical evaluation, including slit-lamp and ophthalmoscopy examinations, was performed. Results: Over the study period of 12 weeks, the mean area under the plasma concentration-time curve was 45.7% higher, and the maximum plasma concentration was 17.2% lower for the animals treated with 40-wt% PA 16-mm microrods compared to 8-mm microrods (251.44 versus 172.54 hours × nanograms per milliliter and 8.53 versus 10.30 ng/mL, respectively). The PA release was significantly below the levels of assumed toxicity. There was no significant difference in the time to reach maximum concentration between the 8- and 16-mm microrod groups (7.33 and 8 hours; P = 0.421). Findings from clinical evaluation, hematology, and histopathology showed no ocular side effects and no significant adverse systemic effects. Conclusion: The PA biodegradable microrods demonstrated safe toxicokinetics even with the larger size implant containing a higher amount of drug. The PA implant may be considered as a safe alternative to the application of topical PA eyedrops. Translational Relevance: The results provide the evidence of the safety of implanting a steroid delivery system subconjunctively, offering an alternative to topical PA eyedrops. |
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School of Materials Science & Engineering |
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School of Materials Science & Engineering Liu, Yu-Chi Ng, Anthony Herr Cheun Ng, Xu Wen Yan, Peng Venkatraman, Subbu Subramanian Mehta, Jodhbir Singh Wong, Tina Tzee Ling |
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Article |
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Liu, Yu-Chi Ng, Anthony Herr Cheun Ng, Xu Wen Yan, Peng Venkatraman, Subbu Subramanian Mehta, Jodhbir Singh Wong, Tina Tzee Ling |
author_sort |
Liu, Yu-Chi |
title |
Evaluation of a Sustained-release Prednisolone Acetate Biodegradable Subconjunctival Implant in a Non-Human Primate Model |
title_short |
Evaluation of a Sustained-release Prednisolone Acetate Biodegradable Subconjunctival Implant in a Non-Human Primate Model |
title_full |
Evaluation of a Sustained-release Prednisolone Acetate Biodegradable Subconjunctival Implant in a Non-Human Primate Model |
title_fullStr |
Evaluation of a Sustained-release Prednisolone Acetate Biodegradable Subconjunctival Implant in a Non-Human Primate Model |
title_full_unstemmed |
Evaluation of a Sustained-release Prednisolone Acetate Biodegradable Subconjunctival Implant in a Non-Human Primate Model |
title_sort |
evaluation of a sustained-release prednisolone acetate biodegradable subconjunctival implant in a non-human primate model |
publishDate |
2018 |
url |
https://hdl.handle.net/10356/88205 http://hdl.handle.net/10220/44578 |
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1772828408147869696 |