<br>可穿戴渗透微针贴片在动物模型中提供高容量持续药物递送,Science Translational Medicine

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可穿戴渗透微针贴片在动物模型中提供高容量持续药物递送
Science Translational Medicine ( IF 15.8 ) Pub Date : 2024-11-27 , DOI: 10.1126/scitranslmed.adp3611
Sheng Zhao _{1,

2} , Ziyi Lu _{1,

3} , Ruisi Cai ₁ , Hui Wang ₁ , Shukun Gao ₁ , Changwei Yang ₁ , Ying Zhang ₁ , Bowen Luo ₁ , Wentao Zhang ₁ , Yinxian Yang ₁ , Shenqiang Wang ₁ , Tao Sheng ₁ , Shiqi Wang ₁ , Jiahuan You ₁ , Ruyi Zhou _{1,

2} , Huimin Ji ₂ , Haoning Gong _{1,

2} , Xiao Ye ₄ , Jicheng Yu _{1,

2,

3,

5} , Hong-Hu Zhu _{6,

7} , Yuqi Zhang _{1,

8} , Zhen Gu _{1,

2,

3,

5,

9,

10,

11}

Affiliation

State Key Laboratory of Advanced Drug Delivery and Release Systems, Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Jinhua Institute of Zhejiang University, Jinhua 321299, China.
Department of General Surgery, Sir Run-Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China.
Key Laboratory for Diagnosis and Treatment of Endocrine Gland Diseases of Zhejiang Province, Geriatric Medicine Center, Department of Endocrinology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou 310014, China.
Liangzhu Laboratory, Zhejiang University, Hangzhou 311121, China.
Department of Hematology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China.
Chinese Institutes for Medical Research, Beijing 100069, China.
Department of Burns and Wound Care Center, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.
MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310058, China.
Engineering Research Center of Innovative Anticancer Drugs, Ministry of Education, Hangzhou 310018, China.
Institute of Fundamental and Transdisciplinary Research Zhejiang University, Zhejiang University, Hangzhou 310058, China.

在治疗窗口内维持稳定的血浆药物浓度对于药物疗效至关重要。在这里，我们开发了一种可穿戴渗透微针（OMN）贴片，可在不使用电子元件的情况下支持至少 24 小时的持续给药。OMN 贴剂利用渗透压驱动力，通过三个直径小于 200 微米的空心微针将药物溶液输送到皮肤中。药物释放速率与渗透原和药物的组成和浓度以及分隔低溶质和高溶质隔室的半透膜的物理性质有关。OMN 贴剂在大鼠和小鼠体内释放肽类药物艾塞那肽 24 h，而皮下注射导致血浆药物浓度爆发释放和快速下降。艾塞那肽的 OMN 释放改善了糖尿病小鼠模型的血糖控制，与药物的持续有效血浆浓度一致。连续释放小分子化疗药物阿糖胞苷比皮下注射更有效地减少了小鼠急性髓性白血病的进展。对犬科动物 OMN 贴剂的进一步评估表明，连续 24 小时服用高达 225 毫克的阿糖胞苷，满足临床要求（每天 150 至 300 毫克）。人类参与者对 OMN 贴剂的耐受性良好，对皮肤的疼痛或刺激最小，并且明确偏好其他给药途径。这种可穿戴的药物输送系统可以为稳定、方便和安全的大剂量药物释放提供平台。

"点击查看英文标题和摘要"

A wearable osmotic microneedle patch provides high-capacity sustained drug delivery in animal models

The maintenance of stable plasma drug concentrations within a therapeutic window can be critical for drug efficacy. Here, we developed a wearable osmotic microneedle (OMN) patch to support sustained drug dosing for at least 24 hours without the use of electronic components. The OMN patch uses an osmotic pressure driving force to deliver drug solution into the skin through three hollow microneedles with diameters of less than 200 micrometers. The rate of drug release was related to the composition and concentration of the osmogen and drug and to the physical properties of the semipermeable membrane separating the low- and high-solute compartments. The OMN patch released the peptide drug exenatide in rats and mice for 24 hours, whereas subcutaneous injection resulted in a burst release and rapid decline in the plasma drug concentration. OMN release of exenatide improved glycemic control in a diabetic mouse model consistent with a sustained effective plasma concentration of the drug. Continuous release of the small-molecule chemotherapeutic drug cytarabine reduced the progression of acute myeloid leukemia in mice more effectively than subcutaneous injection. Further evaluation of the OMN patch in canines demonstrated continuous dosing of cytarabine up to 225 milligrams for 24 hours, satisfying clinical requirements (150 to 300 milligrams daily). OMN patches were well tolerated in human participants with minimal pain or irritation of the skin and a stated preference over other administration routes. This wearable drug delivery system could provide a platform for stable high-dose drug release with convenience and safety.

更新日期：2024-11-27

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