Development of Tamoxifen In Situ Gel Nanoemulsion for Ocular Delivery in Photoreceptor Degeneration Disorder: In Vitro Characterization, 131I-Radiolabeling, and In Vivo Biodistribution Studies,Journal of Pharmaceutical Innovation

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Development of Tamoxifen In Situ Gel Nanoemulsion for Ocular Delivery in Photoreceptor Degeneration Disorder: In Vitro Characterization, 131I-Radiolabeling, and In Vivo Biodistribution Studies
Journal of Pharmaceutical Innovation ( IF 2.7 ) Pub Date : 2022-04-16 , DOI: 10.1007/s12247-022-09638-w
Mohamed H. Aboumanei ₁ , Ashgan Fouad Mahmoud ₁

Affiliation

Purpose

The aim of our work is to develop an in situ ocular gellan gum–based nanoemulsion (NE) of tamoxifen TAM as an alternative drug delivery system to the oral route for the treatment of photoreceptor degeneration disorder.

Method

Six pseudoternary phase diagrams were developed using oil (oleic acid), surfactants (Tween 80 or Tween 20), a co-surfactant (polyethylene glycol 400), and water. The particle size, polydispersity index, and zeta potential of the developed systems were all measured. The safety of ocular application of the optimum system was established via in vivo histopathological investigation. To track the biodistribution of the optimum gel, iodine-131 (¹³¹I) was incorporated into the gel via coupling with TAM via direct electrophilic substitution reaction.

Results

Based on the obtained results, TAMNE-1 was chosen as the optimal system, with PS = 140.20 ± 1.50 nm, ZP = − 27.86 ± 1.13 mV, and PDI = 0.20 ± 0.00%. In vitro release displayed a prolonged and sustained release of TAMNE-1 gel compared to TAM solution (plain eye drop). Transparent in situ TAMNE-1 gel was developed after the incorporation of the TAMNE-1 system into gellan gum aqueous solution (0.3% w/w). In this study, TAM was successfully radiolabeled with ¹³¹I for subsequent evaluation of the efficacy of the developed in situ gel system (TAMNE-1 gel) in vivo. The developed TAMNE-1 gel system was nonirritant and safe and the biodistribution studies showed better retention of TAMNE-1 gel than plain TAM eye drops.

Conclusion

The developed TAMNE-1 gel is able to enhance the ocular bioavailability of TAM and can go further with clinical evaluation.

Graphic Abstract

中文翻译：

开发他莫昔芬原位凝胶纳米乳剂用于光感受器变性障碍的眼部递送：体外表征、131I-放射性标记和体内生物分布研究

目的

我们工作的目的是开发一种他莫昔芬 TAM 的原位眼用结冷胶纳米乳剂 (NE)，作为口服途径的替代药物递送系统，用于治疗光感受器变性障碍。

方法

使用油（油酸）、表面活性剂（吐温 80 或吐温 20）、助表面活性剂（聚乙二醇 400）和水开发了六个假三元相图。对所开发系统的粒径、多分散性指数和 zeta 电位进行了测量。通过体内组织病理学研究确定了最佳系统眼部应用的安全性。为了跟踪最佳凝胶的生物分布，碘131 ( ¹³¹ I) 通过直接亲电取代反应与TAM 偶联而掺入凝胶中。

结果

根据获得的结果，选择 TAMNE-1 作为最佳系统，PS = 140.20 ± 1.50 nm，ZP = - 27.86 ± 1.13 mV，PDI = 0.20 ± 0.00%。与 TAM 溶液（普通滴眼液）相比，体外释放显示 TAMNE-1 凝胶的延长和持续释放。在将 TAMNE-1 系统掺入结冷胶水溶液 (0.3% w/w) 后形成透明的原位 TAMNE-1 凝胶。在这项研究中，TAM 成功地用¹³¹ I 进行了放射性标记，用于随后评估开发的原位凝胶系统（TAMNE-1 凝胶）在体内的功效。开发的 TAMNE-1 凝胶系统无刺激性和安全性，生物分布研究表明 TAMNE-1 凝胶比普通 TAM 滴眼液具有更好的保留性。