Department of Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy, Reynolds Medical Building, Texas A&M University, Mailstop 1114, College Station, TX, USA.
Department of Small Animal Clinical Sciences, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX, USA.
Sci Adv. 2020 Aug 26;6(35):eabb7878. doi: 10.1126/sciadv.abb7878. eCollection 2020 Aug.
Novel approaches circumventing blood-ocular barriers in systemic drug delivery are lacking. We hypothesize receptor-mediated delivery of curcumin (CUR) across intestinal and ocular barriers leads to decreased inflammation in a model of lens-induced uveitis. CUR was encapsulated in double-headed polyester nanoparticles using gambogic acid (GA)-coupled polylactide-co-glycolide (PLGA). Orally administered PLGA-GA-CUR led to notable aqueous humor CUR levels and was dosed (10 mg/kg twice daily) to adult male beagles ( = 8 eyes) with induced ocular inflammation. Eyes were evaluated using a semiquantitative preclinical ocular toxicology scoring (SPOTS) and compared to commercial anti-inflammatory treatment (oral carprofen 2.2 mg/kg twice daily) ( = 8) and untreated controls ( = 8). PLGA-GA-CUR offered improved protection compared with untreated controls and similar protection compared with carprofen, with reduced aqueous flare, miosis, and chemosis in the acute phase (<4 hours). This study highlights the potential of PLGA-GA nanoparticles for systemic drug delivery across ocular barriers.
目前缺乏克服全身药物递送中血眼屏障的新方法。我们假设姜黄素 (CUR) 通过肠道和眼屏障的受体介导递送可导致晶状体诱导性葡萄膜炎模型中的炎症减轻。使用 Gambogic 酸 (GA) 偶联的聚乳酸-共-乙醇酸 (PLGA) 将 CUR 包封在双头聚酯纳米粒子中。口服给予 PLGA-GA-CUR 可导致房水中 CUR 水平显著升高，并以 10 mg/kg 每日两次的剂量对诱导眼内炎症的成年雄性比格犬（= 8 只眼）进行给药。使用半定量临床前眼毒性评分 (SPOTS) 对眼睛进行评估，并与商业抗炎治疗（口服卡洛芬 2.2 mg/kg 每日两次）（= 8 只眼）和未治疗对照组（= 8 只眼）进行比较。与未治疗对照组相比，PLGA-GA-CUR 提供了更好的保护作用，与卡洛芬的保护作用相似，在急性期（<4 小时）减少了房水闪光、瞳孔缩小和结膜水肿。这项研究强调了 PLGA-GA 纳米粒子在全身药物递送至眼屏障中的潜力。
