Development of a conjunctival contact–type drug delivery device for latanoprost using hyaluronic acid

Effective topical drug delivery is crucial for glaucoma treatment, necessitating more convenient methods to enhance patient compliance. This study evaluates the efficacy and safety of using freeze-dried hyaluronic acid (HA) as a carrier for a novel conjunctival-contact drug delivery system. We developed HA tablets loaded with latanoprost (HA-latanoprost) and verified the concentration using high-performance liquid chromatography. Twenty mice (C57BL6) were divided into four groups (<i>n</i> = 5 per group): normal saline (group 1), control HA tablet (group 2), Xalatan™ (group 3), and HA-latanoprost tablet (group 4). Treatments were administered to the right eyes, with the left eyes serving as no-treatment controls. Intraocular pressure (IOP) and irritation (measured by scratching motions) were monitored for 10 days. On day 10, we quantified gene expression of inflammatory cytokines and IOP-affecting proteins using polymerase chain reaction, and performed histological and immunohistochemical analyses. Results showed that IOP was significantly lower in groups 3 and 4 compared to the other groups, with group 4 exhibiting the greatest reduction by day 10. Group 4 also experienced less irritation. Additionally, group 4 had lower expression of inflammatory cytokine genes and higher expression of IOP-lowering protein genes compared to group 3. No significant side effects were observed in any group. Overall, HA-latanoprost effectively lowered IOP and reduced ocular irritation more than latanoprost eyedrops in mice. However, these results are based on animal testing, so further development is needed for clinical use.

有效的局部给药对于青光眼治疗至关重要，亟需开发更便捷的给药方式以提升患者依从性。本研究评估了以冻干透明质酸（HA）作为载体构建新型结膜接触型给药系统的有效性与安全性。我们制备了负载拉坦前列素的HA片剂（HA-latanoprost），并通过高效液相色谱法对其药物浓度进行了验证。将20只C57BL/6小鼠随机分为4组（每组n=5）：生理盐水组（第1组）、空白HA片剂组（第2组）、适利达®（Xalatan™）组（第3组）以及HA-latanoprost片剂组（第4组）。给药方式为右眼给予受试制剂，左眼作为未处理对照。连续10天监测小鼠的眼内压（IOP）及眼部刺激情况（以抓挠动作作为评估指标）。于给药第10天，采用聚合酶链式反应对炎症细胞因子及眼内压调控相关蛋白的基因表达水平进行定量检测，并开展组织学与免疫组织化学分析。实验结果显示，第3组与第4组的眼内压显著低于其余两组，且至第10天时，第4组的眼内压降幅最为显著；同时第4组的眼部刺激反应更为轻微。此外，与第3组相比，第4组的炎症细胞因子基因表达水平更低，而降眼压蛋白基因的表达水平更高；所有组别均未观察到明显不良反应。综上，在小鼠模型中，HA-latanoprost相较于拉坦前列素滴眼液，可更有效地降低眼内压并减轻眼部刺激。但本研究结果仅基于动物实验，尚需进一步开发方可推进至临床应用。