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Evaluations of therapeutic efficacy of intravitreal injected polylactic-glycolic acid microspheres loaded with triamcinolone acetonide on a rabbit model of uveitis

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Abstract

Conventional treatments of uveitis are not ideal because of the short period of therapeutic efficacy. In the present study, biodegradable polylactic-glycolic acid microspheres loaded with triamcinolone acetonide (TA) were prepared to achieve sustained drug release and their therapeutic efficacy was investigated on a rabbit model of uveitis. TA-loaded microspheres (TA-MS) were prepared by the solvent evaporation method and characterized for encapsulation efficiency, particle size, morphology and in vitro release. The therapeutic efficacy was studied on the rabbit experimental uveitis model based on scoring of the inflammation, aqueous leukocyte counting, aqueous protein determination and histological examination. The TA-MS exhibited smooth and intact surfaces with an average diameter of 50.87 μm. The drug-loading coefficient and encapsulation efficiency were 15.2 ± 0.6 % and 91.24 ± 3.77 %, respectively. The drug release from TA-MS lasted up to 87 days, but only 46 days for TA suspension. The change in surface morphology also showed sustained drug release from TA-MS. TA-MS exhibited improved therapeutic efficacy in lipopolysaccharide -induced uveitis compared to TA suspension, especially in regard to the inhibition of inflammation. The TA-MS had a longer-term therapeutic effect on intraocular inflammation in LPS-induced uveitis in rabbits compared to TA suspension. The results suggested that TA-MS can be developed as a potential sustained-release system for the treatment of uveitis.

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Abbreviations

TA:

Triamcinolone acetonide

MS:

Microspheres

TA-MS:

TA-loaded microshperes

PLGA:

Polylactic-glycolic acid

LPS:

Lipopolysaccharide

AS:

Aseptic saline

EIU:

Endotoxin-induced uveitis

SEM:

Scanning electron microscopy

PVA:

Polyvinyl alcohol

MS-blank:

TA-unloaded microspheres

HPLC:

High-performance liquid chromatography

EE:

Encapsulation efficiency

PBS:

Phosphate-buffered saline

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Acknowledgments

This work was supported by the Program for New Drug R&D (No. 2009ZX09310-001) and Innovation Team of Ministry of Education (No. BMU20110263). The authors thank Dr. Jiying Wang for his critical final manuscript revision.

Conflict of interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Ophthalmology, Peking University Third Hospital, Beijing, 100191, People’s Republic of China

    Wenchang Li & Yuling Liu

  2. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, People’s Republic of China

    Bing He, Wenbing Dai & Qiang Zhang

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  1. Wenchang Li
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Correspondence to Yuling Liu.

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Li, W., He, B., Dai, W. et al. Evaluations of therapeutic efficacy of intravitreal injected polylactic-glycolic acid microspheres loaded with triamcinolone acetonide on a rabbit model of uveitis. Int Ophthalmol 34, 465–476 (2014). https://doi.org/10.1007/s10792-013-9829-0

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  • DOI: https://doi.org/10.1007/s10792-013-9829-0

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