Scholarlink

<p>Excised rabbit, porcine, and bovine eyes were injected in the suprachoroidal space with a cassette of 27 drugs, including 10 beta-blockers, 8 NSAIDs, and 9 corticosteroids, spanning a lipophilicity range (LogD<sub>7.4</sub>: −4.18 to 4.70). Drug concentrations in retina and vitreous humor were quantified by LC-MS/MS on both injected and non-injected sides. Most drugs were detected in both tissues, with higher concentrations on the injected side (0.04–3.69 fraction dose or FD/g) compared to the non-injected side (0.00–0.74 FD/g), after excluding eight outliers (drug–prodrug pairs and unstable drugs). Total retinal concentrations (0.07–1.88 FD/g) exceeded vitreous concentrations (0.02–0.40 FD/g). Across species, delivery decreased with eye diameter (rabbit &gt; porcine &gt; bovine). For individual species, multiple linear regression explained 70–83% of variance in retinal concentrations and 45–62% in vitreous concentrations using drug physicochemical properties. A unified equation incorporating 1/d² (d is eye diameter in cm), lipophilicity (LogD<sub>7.4</sub>), molar solubility (LogS), and total polar surface area (TPSA) predicted concentrations in all species for a given tissue, explaining 74% of retinal and 93% of vitreous variance. Retinal delivery scaled for all species: Log FD/g = -1.121 + 0.255*LogD<sub>7.4</sub> + 0.106*LogS + 0.004*TPSA + 0.395*1/d<sup>2</sup>. Vitreous humor delivery scaled for all species: Log FD/g = -1.898–0.047*LogD<sub>7.4</sub> − 0.051*LogS + 0.001*TPSA + 0.833*1/d<sup>2</sup>. While this study evaluated static barriers, in vivo delivery is expected to be lower due to dynamic clearance mechanisms.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Interspecies scaling of suprachoroidal drug delivery using ocular geometry and drug physicochemical properties

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年1月16日

查看全文
  • Madhoosudan A. Patil,
  • Brock A. Matter,
  • Cleildo Santana,
  • Uday B. Kompella

摘要

Excised rabbit, porcine, and bovine eyes were injected in the suprachoroidal space with a cassette of 27 drugs, including 10 beta-blockers, 8 NSAIDs, and 9 corticosteroids, spanning a lipophilicity range (LogD7.4: −4.18 to 4.70). Drug concentrations in retina and vitreous humor were quantified by LC-MS/MS on both injected and non-injected sides. Most drugs were detected in both tissues, with higher concentrations on the injected side (0.04–3.69 fraction dose or FD/g) compared to the non-injected side (0.00–0.74 FD/g), after excluding eight outliers (drug–prodrug pairs and unstable drugs). Total retinal concentrations (0.07–1.88 FD/g) exceeded vitreous concentrations (0.02–0.40 FD/g). Across species, delivery decreased with eye diameter (rabbit > porcine > bovine). For individual species, multiple linear regression explained 70–83% of variance in retinal concentrations and 45–62% in vitreous concentrations using drug physicochemical properties. A unified equation incorporating 1/d² (d is eye diameter in cm), lipophilicity (LogD7.4), molar solubility (LogS), and total polar surface area (TPSA) predicted concentrations in all species for a given tissue, explaining 74% of retinal and 93% of vitreous variance. Retinal delivery scaled for all species: Log FD/g = -1.121 + 0.255*LogD7.4 + 0.106*LogS + 0.004*TPSA + 0.395*1/d2. Vitreous humor delivery scaled for all species: Log FD/g = -1.898–0.047*LogD7.4 − 0.051*LogS + 0.001*TPSA + 0.833*1/d2. While this study evaluated static barriers, in vivo delivery is expected to be lower due to dynamic clearance mechanisms.