Preclinical In Vivo Safety of Poly-Phosphorylated Superlubrication Vectors for the Treatment of Osteoarthritis.

IF 1.4 4区医学 Q3 PATHOLOGY

Toxicologic Pathology Pub Date : 2022-08-01 Epub Date: 2022-06-21 DOI:10.1177/01926233221105393

Yuval Ramot, Oleg Dolkart, Michal Steiner, Sabrina Jahn, Ronit Goldberg, Orna Cacical, Yossi Lavie, Nati Ezov, Gabi Agar, Abraham Nyska

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引用次数: 0

Abstract

Osteoarthritis (OA) can lead to a significant functional disability. Poly[2-(methacryloyloxy)ethyl phosphorylcholine] (pMPC) liposomes are a novel treatment modality for OA, intended to restore the natural lubrication properties of articular cartilage. Here, we report on two studies aimed to assess the local and systemic safety and toxicity of pMPCylated liposomes in comparison with physiological saline, in Sprague-Dawley (SD) rats and in sheep after a single intra-articular (IA) injection. The animals were sacrificed after 1 and 6 weeks (rats) and 3 and 6 weeks (sheep). No signs of toxicity or abnormal clinical findings were observed. Histopathological evaluation revealed no signs of reactivity or abnormal findings in the injected joints or in any other organs. In conclusion, a single IA injection of the pMPCylated liposomes demonstrated an excellent safety profile and did not result in local reactivity or systemic toxicity, thus supporting its further development for use in humans.

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多磷酸化超润滑载体治疗骨关节炎的临床前体内安全性研究。

骨关节炎(OA)可导致严重的功能残疾。聚[2-(甲基丙烯酰氧基)乙基磷酸胆碱](pMPC)脂质体是一种新的OA治疗方式，旨在恢复关节软骨的自然润滑特性。在这里，我们报告了两项研究，目的是在Sprague-Dawley (SD)大鼠和绵羊单次关节内注射(IA)后，评估pMPCylated脂质体与生理盐水的局部和全身安全性和毒性。动物分别于1、6周(大鼠)和3、6周(绵羊)处死。没有观察到毒性迹象或异常临床表现。组织病理学评估显示，在注射关节或任何其他器官中没有反应性或异常发现的迹象。总之，单次IA注射pMPCylated脂质体显示出极好的安全性，不会导致局部反应性或全身毒性，因此支持其进一步开发用于人类。

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

Toxicologic Pathology 医学-病理学

CiteScore

4.70

自引率

20.00%

发文量

审稿时长

6-12 weeks

期刊介绍： Toxicologic Pathology is dedicated to the promotion of human, animal, and environmental health through the dissemination of knowledge, techniques, and guidelines to enhance the understanding and practice of toxicologic pathology. Toxicologic Pathology, the official journal of the Society of Toxicologic Pathology, will publish Original Research Articles, Symposium Articles, Review Articles, Meeting Reports, New Techniques, and Position Papers that are relevant to toxicologic pathology.