Development of a Temperature and pH Dual-Sensitive In-Situ Gel for Treating Allergic Conjunctivitis

IF 3.4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech Pub Date : 2024-09-25 DOI:10.1208/s12249-024-02931-6

Yanpeng Zhu, Yinghui Liu, Yongyue Wang, Tingting Chen, Xuerui Ma, Ji Li, Dongkai Wang

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引用次数: 0

Abstract

The purpose of this study was to improve the efficacy of olopatadine hydrochloride (OT) in treating allergic conjunctivitis (AC). To achieve this goal, we developed an eye formulation without antimicrobial agents using a temperature-pH dual-sensitive in situ gel technology combined with heat sterilization. Various types of carbomers were evaluated and their optimal doses determined. The prescription containing poloxamer 407 (P407) and poloxamer 188 (P188) was optimized using central composite design for response surface methodology (CCD-RSM). The final optimized dual-sensitive in situ gel (TP-gel) consisted of 0.1% olopatadine hydrochloride, 18.80% P407, 0.40% P188, 0.30% Pemulen™TR-1(TR-1), 4.0% mannitol, and 0.08% Tri(hydroxymethyl)aminomethane(Tris).Sterilization was performed at a temperature of 121℃ for a duration of 20 min. Experimental results showed that TP-gel had good safety profile and remained on the ocular surface for approximately (65.83 ± 8.79) minutes, which is four times longer than eye drops. The expression levels of IL-13, IL-17, and OVA-IgE in mouse ocular tissues with allergic conjunctivitis treated with TP-gel were significantly reduced. This suggests that TP-gel has the potential to be an effective treatment method for allergic conjunctivitis.

Graphical Abstract

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开发治疗过敏性结膜炎的温度和酸碱度双敏感原位凝胶

本研究旨在提高盐酸奥洛他定（OT）治疗过敏性结膜炎（AC）的疗效。为实现这一目标，我们开发了一种不含抗菌剂的眼用制剂，该制剂采用了温度-pH 双敏感原位凝胶技术，并结合了加热灭菌技术。我们对各种类型的卡波姆进行了评估，并确定了其最佳剂量。采用响应面方法的中心复合设计（CCD-RSM）对含有聚氧乙烯 407（P407）和聚氧乙烯 188（P188）的处方进行了优化。最终优化的双敏原位凝胶（TP-gel）由 0.1% 的盐酸奥洛他定、18.80% 的 P407、0.40% 的 P188、0.30% 的 Pemulen™TR-1（TR-1）、4.0% 的甘露醇和 0.08% 的三羟甲基氨基甲烷（Tris）组成。实验结果表明，TP-凝胶具有良好的安全性，在眼球表面的停留时间约为（65.83 ± 8.79）分钟，是滴眼液的四倍。使用 TP 凝胶治疗过敏性结膜炎的小鼠眼组织中 IL-13、IL-17 和 OVA-IgE 的表达水平显著降低。这表明，TP-凝胶有可能成为治疗过敏性结膜炎的一种有效方法。

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来源期刊

AAPS PharmSciTech 医学-药学

CiteScore

6.80

自引率

3.00%

发文量

264

审稿时长

2.4 months

期刊介绍： AAPS PharmSciTech is a peer-reviewed, online-only journal committed to serving those pharmaceutical scientists and engineers interested in the research, development, and evaluation of pharmaceutical dosage forms and delivery systems, including drugs derived from biotechnology and the manufacturing science pertaining to the commercialization of such dosage forms. Because of its electronic nature, AAPS PharmSciTech aspires to utilize evolving electronic technology to enable faster and diverse mechanisms of information delivery to its readership. Submission of uninvited expert reviews and research articles are welcomed.