Combination of Ketorolac Tromethamine and Prednisolone-Loaded PLGA Nanocomposite for Effective Chronic Pain Relief in Mice.

IF 6.5 2区医学 Q1 NANOSCIENCE & NANOTECHNOLOGY

International Journal of Nanomedicine Pub Date : 2025-06-27 eCollection Date: 2025-01-01 DOI:10.2147/IJN.S515452

Tuyet-Nhi Do, Yen-Chin Liu, Yu-Che Chuang, Tsung-Lin Tsai, Ping-Ching Wu

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引用次数: 0

Abstract

Introduction: Chronic pain is a complex condition that requires timely and effective management to prevent long-term emotional, social, and economic consequences. This study aims to develop a poly(lactic-co-glycolic acid) (PLGA)-based nanocomposite co-loaded with ketorolac tromethamine (KT) and prednisolone (PRED) to improve therapeutic efficacy and reduce systemic side effects associated with conventional treatments.

Methods: KT-PRED-PLGA nanoparticles were synthesized via a double emulsion method and characterized for their physicochemical properties and biocompatibility. A chronic inflammatory pain model was established in ICR mice using Complete Freund's Adjuvant (CFA). Mechanical pain thresholds were evaluated using Dixon's up-and-down method. Histopathological and immunohistochemical analyses were performed to evaluate systemic toxicity and inflammation-related protein expression.

Results: The KT-PRED-PLGA nanoparticles exhibited favorable characteristics, including a mean particle size of 166.2 ± 8.0 nm, a polydispersity index of 0.14, a zeta potential of -15.8 ± 0.3 mV, and encapsulation efficiency exceeding 80%. The nanoparticles sustained drug release up to 92.5% over 120 h. In vitro assays demonstrated the KT-PRED-PLGA nanoparticles revealed high biocompatibility in Vero cells after 72 h of exposure. In vivo experiments demonstrated significantly reduced pain behaviors and tissue inflammation, with minimal toxicity. Behavioral assessments confirmed enhanced analgesic and anti-allodynic effects over the free drugs. Reduced expression of cyclooxygenases (COX-1 and COX-2) and prostaglandin E₂ (PGE₂) in hind paw tissues confirmed improved anti-inflammatory activity.

Conclusion: KT-PRED-PLGA nanoparticles offer safe, sustained analgesia with enhanced therapeutic efficacy and reduced systemic toxicity, highlighting their strong potential for future clinical translation in chronic pain therapy.

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酮咯酸Tromethamine和强的松龙负载PLGA纳米复合材料联合有效缓解小鼠慢性疼痛。

慢性疼痛是一种复杂的疾病，需要及时有效的管理，以防止长期的情绪、社会和经济后果。本研究旨在开发一种以聚乳酸-羟基乙酸（PLGA）为基础的纳米复合材料，共负载酮咯酸tromethamine （KT）和强的松龙（PRED），以提高治疗效果并减少常规治疗相关的全身副作用。方法：采用双乳法制备了KT-PRED-PLGA纳米颗粒，并对其理化性质和生物相容性进行了表征。采用完全弗氏佐剂（CFA）建立ICR小鼠慢性炎症性疼痛模型。采用Dixon上下法评估机械痛阈。进行组织病理学和免疫组织化学分析以评估全身毒性和炎症相关蛋白的表达。结果：KT-PRED-PLGA纳米颗粒的平均粒径为166.2±8.0 nm，多分散性指数为0.14，zeta电位为-15.8±0.3 mV，包封效率超过80%。在120小时内，纳米颗粒的药物缓释率高达92.5%。体外实验表明，在暴露72小时后，KT-PRED-PLGA纳米颗粒在Vero细胞中显示出很高的生物相容性。体内实验表明，显著减少疼痛行为和组织炎症，毒性最小。行为评估证实，与游离药物相比，镇痛和抗异动作用增强。后爪组织环氧化酶（COX-1和COX-2）和前列腺素E2 （PGE2）的表达降低证实了抗炎活性的提高。结论：KT-PRED-PLGA纳米颗粒提供安全、持续的镇痛，增强了治疗效果，降低了全身毒性，突出了其在未来慢性疼痛治疗的临床应用潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

International Journal of Nanomedicine NANOSCIENCE & NANOTECHNOLOGY-PHARMACOLOGY & PHARMACY

CiteScore

14.40

自引率

3.80%

发文量

511

审稿时长

1.4 months

期刊介绍： The International Journal of Nanomedicine is a globally recognized journal that focuses on the applications of nanotechnology in the biomedical field. It is a peer-reviewed and open-access publication that covers diverse aspects of this rapidly evolving research area. With its strong emphasis on the clinical potential of nanoparticles in disease diagnostics, prevention, and treatment, the journal aims to showcase cutting-edge research and development in the field. Starting from now, the International Journal of Nanomedicine will not accept meta-analyses for publication.