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• W2171830128 abstract "Purpose: HM-3, an RGD-modified endostatin-derived polypeptide, is a potent angiogenesis inhibitor synthesized in our laboratory. This study investigated the HM-3 pharmacokinetics of intravitreally administered in mice eyes as an anti-angiogenesis drug for age-related macular degeneration.Materials and methods: A total of 288 C57BL/6J mice were evaluated and divided into four groups. Each mouse in different groups received single bilateral intravitreal injection with HM-3. The concentrations of HM-3 in choroid/sclera, retina and serum were determined by indirect competitive enzyme-linked immunosorbent assay.Results: After intravitreal administration of doses of 0, 10, 20 and 40 μg/eye HM-3, the observed maximum concentration (Cmax) was 12.98 ± 1.42, 27.87 ± 3.64 and 55.96 ± 11.94 ng/mg, respectively; and the total area under the curve (AUCtot) was 739.23 ± 190.32, 1171.74 ± 528.75 and 1777.71 ± 511.64 h ng/mg; the elimination half-life (T1/2) in retina was 104.85 ± 36.90, 107.42 ± 35.25 and 101.12 ± 15.82 h; the mean residence time (MRT) was 172.46 ± 63.80, 164.70 ± 52.72 and 181.32 ± 26.01 h, respectively. In choroid/sclera, the Cmax was 5.29 ± 0.34, 6.29 ± 1.87 and 8.14 ± 0.71 ng/mg, respectively; AUCtot was 579.03 ± 56.50, 762.20 ± 201.09 and 720.91 ±243.87 h ng/mg; T1/2 was 54.04 ± 25.99, 59.33 ± 24.46 and 47.10 ± 10.00 h, respectively; MRT was 139.98 ± 23.93, 155.43 ± 17.81 and 136.45 ± 18.17 h, respectively. But in serum, the Cmax was 482.00 ± 38.97, 493.94 ± 97.64 and 1033.10 ± 276.33 ng/ml, respectively; AUCtot was 21128.55 ± 4683.68, 53444.57 ± 16963.99 and 53164.84 ±1535.06 h ng/ml; T1/2 was 48.39 ± 14.89, 47.96 ± 12.97 and 49.98 ± 30.07 h, respectively; MRT was 108.6 ± 47.17, 159.76 ± 18.82 and 125.33 ± 21.41 h, respectively.Conclusions: The pharmacokinetic profiles of intravitreal administration HM-3 provide the basis for the development of reasonable dosing regimens of clinical choroidal neovascularization (CNV) treatment. However, the vitreous and blood retinal barrier might be barriers to drug distribution and diffusion. In addition, fluid flow for the anterior transport and choroidal blood circulation might play important roles for multiple peaking. Carrying out the research into pharmacokinetics of HM-3 provides the information for laying down drug delivery scheme in mice model of CNV." @default.
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• W2171830128 date "2014-02-21" @default.
• W2171830128 modified "2023-09-25" @default.
• W2171830128 title "Pharmacokinetics of HM-3 After Intravitreal Administration in Mice" @default.
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• W2171830128 doi "https://doi.org/10.3109/02713683.2014.883411" @default.
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