制备和评估用于器官移植的新型口服他克莫司纳米絮凝物,以减少个体差异并提高药物安全性。

IF 5.3 2区 医学 Q1 PHARMACOLOGY & PHARMACY International Journal of Pharmaceutics Pub Date : 2024-10-09 DOI:10.1016/j.ijpharm.2024.124811
Shengjun Mu , Bei Zhang , Ruiqin Huang, Min Li
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引用次数: 0

摘要

器官移植后,患者需要使用免疫抑制剂来防止免疫排斥反应和移植失败。他克莫司(FK506)是一种广泛使用的免疫抑制剂,以其强大的免疫抑制作用和较窄的治疗范围而闻名。监测 FK506 的血药浓度对于避免肾毒性至关重要。本研究采用微流控方法开发了一种新型 FK506 纳米药物(FK506 耳蜗片),以减少个体差异并提高药物安全性。FK506 cochleates的粒径为(183.3 ± 1.4)nm,zeta电位为-(39.28 ± 2.12)mV,封装效率超过85%。在冻干粉末形式下,FK506耳蜗片的粒度可保持长达12周。小角 X 射线散射(SAXS)实验证实了加入钙溶液后形成的蜗囊。体外释放研究表明,FK506 可从耳蜗载体中持续释放。此外,蜗壳载体还能保护 FK506 免受胃酸的影响,并在肠道中缓慢释放药物。大鼠口服 FK506 后,FK506 共沸物表现出持续释放的特性,并在脾脏和淋巴结--FK506 药理作用的关键解剖部位--积聚。重要的是,FK506蜗蜗片剂能显著延长兔心脏移植模型的存活时间,同时保持良好的安全性。总之,FK506蜗牛酸盐在提高治疗器官移植的药物安全性方面表现出了巨大的潜力。
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Preparation and evaluation of novel oral tacrolimus nanocochleates for organ transplantation to reduce individual differences and improve drug safety
After organ transplantation, patients require treatment with immunosuppressive drugs to prevent immune rejection and transplantation failure. Tacrolimus (FK506) is a widely used immunosuppressant known for its potent immunosuppressive effect and narrow therapeutic range. Monitoring of FK506 blood concentrations is essential to avoid nephrotoxicity. In this study, a novel FK506 nanomedicine (FK506 cochleates) was developed using a microfluidic method to reduce variability among individuals and improve drug safety. The particle size of FK506 cochleates was (183.3 ± 1.4) nm, the zeta potential was −(39.28 ± 2.12) mV, and the encapsulation efficiency was more than 85 %. Particle size of FK506 cochleates could be maintained for up to 12 weeks in freeze-dried powder form. Small-angle X-ray scattering (SAXS) experiment confirmed the formation of cochleates by adding calcium solution. In vitro release studies demonstrated a sustained-release profile of FK506 from the cochleates carrier. Furthermore, the cochleates carrier could protect FK506 from the influence of stomach acid and slowly release the drug in the intestine. After oral administration, FK506 cochleates exhibited sustained-release properties in rats, accumulating in the spleen and lymph nodes − key anatomical sites for FK506’s pharmacological action. Importantly, FK506 cochleates significantly prolonged the survival time in the rabbit heart transplantation model while maintaining good safety profiles. In conclusion, the FK506 cochleates showed promising potential for enhancing drug safety in therapeutic organ transplantation.
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来源期刊
CiteScore
10.70
自引率
8.60%
发文量
951
审稿时长
72 days
期刊介绍: The International Journal of Pharmaceutics is the third most cited journal in the "Pharmacy & Pharmacology" category out of 366 journals, being the true home for pharmaceutical scientists concerned with the physical, chemical and biological properties of devices and delivery systems for drugs, vaccines and biologicals, including their design, manufacture and evaluation. This includes evaluation of the properties of drugs, excipients such as surfactants and polymers and novel materials. The journal has special sections on pharmaceutical nanotechnology and personalized medicines, and publishes research papers, reviews, commentaries and letters to the editor as well as special issues.
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