Laboratory of Pharmaceutical Technology, Dept. of Pharmacy, University of Patras, Rio 26510, Patras, Greece.
Laboratory of Optics and Vision, Department of Medicine, University of Crete, Heraklion, Greece.
Eur J Pharm Sci. 2017 Nov 15;109:324-333. doi: 10.1016/j.ejps.2017.08.028. Epub 2017 Aug 31.
A novel Flurbiprofen (FLB)-in-liposome-in-hydrogel formulation was developed, as a method to sustain the release and increase the ocular bioavailability of FLB following intravitreal injection. For this, FLB loading into liposomes was optimized and liposomes were entrapped in thermosensitive hydrogels consisted of Pluronic F-127 (P). FLB solution, liposomes, and FLB dissolved in hydrogel were also used as control formulations. Actively loaded liposomes were found to be optimal for high FLB loading and small size, while in vitro studies revealed that P concentration of 18% (w/v) was best to retain the integrity of the hydrogel-dispersed liposome, compared to a 20% concentration. The in vitro release of FLB was significantly sustained when FLB-liposomes were dispersed in the hydrogel compared to hydrogel dissolved FLB, as well as the other control formulations. In vivo studies were carried out in pigmented rabbits which were injected through a 27G needle with 1mg/mL FLB in the different formulation-types. Ophthalmic examinations after intravitreal injection of all FLB formulations, revealed no evidence of inflammation, hemorrhage, uveitis or endophthalmitis. Pharmacokinetic analysis results confirm that the hybrid drug delivery system increases the bioavailability (by 1.9 times compared to solution), and extends the presence of the drug in the vitreous cavity, while liposome and hydrogel formulations demonstrate intermediate performance. Furthermore the hybrid system increases MRT of FLB in aqueous humor and retina/choroid tissues, compared to all the control formulations. Currently the potential therapeutic advances of FLB sustained release formulations for IVT administration are being evaluated.
一种新型的氟比洛芬（FLB）-脂质体-水凝胶制剂被开发出来，作为一种在玻璃体内注射后持续释放和增加 FLB 眼内生物利用度的方法。为此，优化了 FLB 包载入脂质体的方法，并将脂质体包封在由泊洛沙姆 F-127（P）组成的温敏水凝胶中。FLB 溶液、脂质体和溶解在水凝胶中的 FLB 也被用作对照制剂。研究发现，主动负载的脂质体具有高 FLB 负载和小粒径的优势，而体外研究表明，与 20%浓度相比，18%（w/v）的 P 浓度最有利于保持水凝胶分散的脂质体的完整性。与溶解在水凝胶中的 FLB 以及其他对照制剂相比，当 FLB 脂质体分散在水凝胶中时，FLB 的体外释放明显得到了持续。在有色兔子中进行了体内研究，这些兔子通过 27G 针头注射 1mg/mL 的不同制剂类型的 FLB。玻璃体内注射所有 FLB 制剂后的眼科检查显示，没有炎症、出血、葡萄膜炎或眼内炎的证据。药代动力学分析结果证实，这种混合药物递送系统增加了生物利用度（与溶液相比增加了 1.9 倍），并延长了药物在玻璃体内腔中的存在时间，而脂质体和水凝胶制剂则表现出中间性能。此外，与所有对照制剂相比，混合系统增加了 FLB 在房水中和视网膜/脉络膜组织中的平均滞留时间（MRT）。目前，正在评估 IVT 给药中 FLB 缓释制剂的潜在治疗进展。
