Pharmacokinetics and tolerance study of intravitreal injection of dexamethasone-loaded nanoparticles in rabbits
Linhua Zhang1, Yue Li2, Chao Zhang1, Yusheng Wang2, Cunxian Song1
1Institute of Biomedical Engineering, Peking Union Medical College and Chinese Academy of Medical Sciences, Tianjin, China; 2Department of Ophthalmology, Institute of Ophthalmology of Chinese PLA, Xijing Hospital, Fourth Military Medical University, Xi’an, China
Abstract: The aim of the study was to investigate the tolerance and pharmacokinetics of dexamethasone (DEX)-loaded poly(lactic acid–co-glycolic acid) nanoparticles (DEX-NPs) in rabbits after intravitreal injection. The DEX-NPs were prepared and characterized in terms of morphology, particle size and size distribution, encapsulation efficiency, and in vitro release. Ophthalmic investigations were performed, including fundus observation and photography, intraocular pressure measurement, and B-scan ocular ultrasonography. There were no abnormalities up to 50 days after administration of DEX-NPs in rabbits. The DEX concentrations in plasma and the ocular tissues such as the cornea, aqueous humor, lens, iris, vitreous humor, and chorioretina were determined by high-pressure liquid chromatography. The DEX-NPs maintained a sustained release of DEX for about 50 days in vitreous and provided relatively constant DEX levels for more than 30 days with a mean concentration of 3.85 mg/L-1. Based on the areas under the curve, the bioavailability of DEX in the experimental group was significantly higher than that in the control group injected with regular DEX. These results suggest that intravitreal injection of DEX-NPs lead to a sustained release of DEX with a high bioavailability, providing a basis for a novel approach to the treatment of posterior segment diseases.
Keywords: dexamethasone, nanoparticles, intravitreal injection, pharmacokinetics
Current treatments of the posterior segment diseases using corticoids are performed by direct injections of corticoid solutions or suspensions. However, direct injections of corticoids into the vitreous often require large boluses and repeated injections to ensure therapeutic levels over an extended period of time, leading to a reduction of patient compliance, or to an increased likelihood of complications. Nanoparticulate drug delivery system would allow a sustained delivery of drugs, thus prolonging the duration of drug action, avoiding the need for frequent intraocular injections and decreasing the risk of complications. In this study, we have investigated the pharmacokinetic behavior and tolerance of dexamethasone-loaded PLGA nanoparticles (DEX-NPs) in ocular tissues and plasma after a single intravitreal injection in rabbits. Our results suggest that intravitreal injection of DEX-NPs lead to a sustained release of DEX with a high bioavailability, providing a basis for a novel approach to the treatment of posterior segment diseases.
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