Purpose: Puerarin (PUR) is a major bioactive ingredient extracted from the root of Pueraria lobata (Willd.) Ohwi, which is known as Gegen in traditional Chinese medicine. Conventional PUR ophthalmic dosage forms such as solutions and suspensions have many drawbacks, including-rapid precorneal elimination of the drug mainly due to lacrimal duct drainage. The purpose of this study is to develop a thermal responsive in situ gel system containing PUR-loaded human albumin nanoparticles (PUR-HSA-NPs ISG).
Methods: The system has the required sol-gel phase transition temperature, and therefore can be used for local ocular administration to treat glaucoma. The formulation was evaluated for its sol-gel transition temperature, viscosity and in vitro release. In vivo eye irritation was evaluated in rabbits. In this study, the animal model of glaucoma was used to evaluate the pharmacodynamics of PUR-HSA-NPs ISG in vivo.
Results: Morphologically, the PUR-HSA-NPs ISG exhibited a normal spherical shape with no aggregation or degradation. It had a mean size of 64.8 nm, and the drug-loading and encapsulation efficiency were 7.1%± 0.3% and 80.7%± 7.4%, respectively. The gelation temperature of the prepared PUR-HSA-NPs ISG thermogelling solutions was 37°C. Meanwhile, the PUR-HSA-NPs ISG showed thixotropic behavior with the downward curve exhibiting lower shear stress values as compared to corresponding points on the upward curve. The pharmacological results showed a continuous reduction of the IOP value for a long time and that the value remained in a lower-level range compared to that in the PUR eye drop group. According to the pharmacodynamic results, the Bcl-2/Bax ratio of the PUR-HSA-NPs ISG group was closest to 1 (0.8798, 24 h), with obvious reduction of tissue cell apoptosis.
Conclusion: Through this study, it was found that PUR-HSA-NPs ISG is an ideal ocular drug delivery system. It is hoped that this product could be further promoted for clinical applications in the future.

Keywords: puerarin, albumin nanoparticles, thermoresponsive in situ gel, ophthalmic delivery


中文翻译：

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葛根素负载白蛋白纳米颗粒热响应原位凝胶眼科给药的开发与评价

用途：葛根素（PUR）是从葛根中提取的主要生物活性成分，在中药中被称为葛根。传统的 PUR 眼科剂型，如溶液剂和混悬剂具有许多缺点，包括主要由于泪道引流导致的角膜前药物快速消除。本研究的目的是开发一种含有 PUR 负载的人白蛋白纳米粒子 (PUR-HSA-NPs ISG) 的热响应原位凝胶系统。
方法：该系统具有所需的溶胶-凝胶相变温度，因此可用于眼部局部给药治疗青光眼。评估了该制剂的溶胶-凝胶转变温度、粘度和体外释放。在兔子中评估了体内眼睛刺激。本研究采用青光眼动物模型评价 PUR-HSA-NPs ISG 在体内的药效学。
结果：在形态学上，PUR-HSA-NPs ISG 呈现出正常的球形，没有聚集或降解。它的平均粒径为64.8 nm，载药率和包封率分别为7.1%±0.3%和80.7%±7.4%。制备的 PUR-HSA-NPs ISG 热凝胶溶液的凝胶温度为 37°C。同时，PUR-HSA-NPs ISG 表现出触变行为，与向上曲线上的相应点相比，向下曲线表现出较低的剪切应力值。药理结果显示，眼压值长期持续下降，与PUR滴眼剂组相比，该值保持在较低水平范围内。根据药效学结果，PUR-HSA-NPs ISG组的Bcl-2/Bax比值最接近1（0.8798，24 h），
结论：通过本研究发现PUR-HSA-NPs ISG是一种理想的眼部给药系统。希望未来该产品能够进一步推广到临床应用。

关键词：葛根素，白蛋白纳米粒，热响应原位凝胶，眼部给药