Pharmacokinetic and Safety Evaluation of a Transscleral Sustained Unoprostone Release Device in Monkey Eyes

Autor: Hirokazu Kaji, Junichi Kawasaki, Toru Nakazawa, Nobuhiro Nagai, Eri Koyanagi, Matsuhiko Nishizawa, Toshiaki Abe, Saaya Saijo, Shinji Yamada
Rok vydání: 2018
Předmět:
Intraocular pressure
medicine.medical_specialty
genetic structures
Drug Evaluation
Preclinical
02 engineering and technology
Dinoprost
Retina
Polyethylene Glycols
03 medical and health sciences
Unoprostone Isopropyl
chemistry.chemical_compound
0302 clinical medicine
Ciliary body
Drug Delivery Systems
Tandem Mass Spectrometry
Ophthalmology
medicine
Electroretinography
Animals
Tissue Distribution
Antihypertensive Agents
Intraocular Pressure
medicine.diagnostic_test
business.industry
Retinal
021001 nanoscience & nanotechnology
eye diseases
Macaca fascicularis
medicine.anatomical_structure
Unoprostone
chemistry
Delayed-Action Preparations
030221 ophthalmology & optometry
Macaca
Methacrylates
sense organs
Choroid
0210 nano-technology
business
Sclera
Tomography
Optical Coherence
medicine.drug
Chromatography
Liquid
Zdroj: Investigative ophthalmologyvisual science. 59(2)
ISSN: 1552-5783
Popis: Purpose We evaluate the ocular tissue distribution and retinal toxicity of unoprostone (UNO) during 12 months, after transscleral sustained-UNO administration using a drug delivery device in monkey eyes. Methods The device consisted of a reservoir, controlled-release cover, and a drug formulation of photopolymerized polyethylene glycol dimethacrylate. Six mg UNO was loaded into the device (length, 17 mm; width, 4.4 mm; height, 1 mm). The concentrations of M1, a primary metabolite of UNO, in the retina, choroid, vitreous, lens, aqueous humor, iris, ciliary body, and plasma were determined by liquid chromatography-tandem mass spectrometry at 3, 6, and 12 months after implantation. Retinal toxicity was evaluated by electroretinography (ERG), optical coherence tomography (OCT), and IOP at preimplantation, and at 6, 9, and 12 months after implantation. Focal ERGs were performed at 9 and 12 months after implantation. Results M1 was detected in the choroid and retina with maximum peaks of 243.2 and 8.41 ng/g at 6 months, respectively. M1 in the ciliary body and iris was detected with maximum peaks of 7.66 and 10.4 ng/g at 6 and 12 months, respectively. Less than 1 ng/mL or ng/g of M1 was detected in the aqueous humor, vitreous, and lens. No changes were observed in retinal function as assessed by ERG, IOP, or macula thickness and retinal histology by OCT examinations during the 12-month period. No differences in focal ERG amplitudes, especially in the macula, were observed. Conclusions The device provided intraocular sustained delivery of UNO for 12 months without producing severe retinal toxicity.
Databáze: OpenAIRE
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