Chauhan Shreya Shashank, Prasad Aditi, Venuganti Venkata Vamsi Krishna
Department of Pharmacy, Birla Institute of Technology and Science (BITS) Pilani, Hyderabad Campus, Hyderabad, Telangana, India.
J Biomed Mater Res A. 2025 Jan;113(1):e37809. doi: 10.1002/jbm.a.37809. Epub 2024 Oct 13.
Sampling of interstitial fluid (ISF) using microneedle (MN) patch offers a pain-free minimally invasive alternative to syringe needle-based blood sample collection. However, there is a challenge in the development of MN patch that provides swelling behavior with sufficient mechanical strength for skin penetration. Here, we report fabrication of MN patch made of biopolymer composite containing iota-carrageenan, gelatin, and polyethylene glycol. Calcium chloride was used as a crosslinker to improve mechanical strength. MN patch was characterized for integrity, swelling behavior, mechanical strength, aspiration of fluid from agarose gel, and the excised porcine ear skin. An array of 361 MNs was able to aspirate 36 ± 5 and 14 ± 1 μL fluid after application in agarose gel matrix and the ex vivo porcine skin model, respectively. MN patch applied in vivo rat model for 30 min resulted in the collection of ISF containing 267 ± 128 mg/dL, 24 ± 13 mg/dL, and 0.6 ± 0.4 mIU/mL of glucose, uric acid and thyroid stimulating hormone (TSH), respectively. The concentration of glucose, uric acid, and TSH in rat blood was found to be 199 ± 47 mg/dL, 8.4 ± 6 mg/dL, and 1.1 ± 0.6 mIU/mL at the same time. Furthermore, MN patch applied on the forearm of 10 healthy human volunteers for 30 min was able to aspirate 32 ± 14 μL of ISF. The concentration of glucose, uric acid, and TSH determined from ISF samples of human volunteers was 64 ± 25 mg/dL, 4.2 ± 4.1 mg/dL, and 0.16 ± 0.08 mIU/mL, respectively. The visual analogue scale (VAS) pain score after MN application was lower compared with hypodermic syringe needle insertion. Taken together, biopolymer composite-based swellable MN patch can be developed for collection of ISF for simultaneous determination of multiple biomolecules in a minimally invasive manner.
使用微针（MN）贴片采集组织间液（ISF）为基于注射器针头的血样采集提供了一种无痛、微创的替代方法。然而，在开发具有足够机械强度以实现皮肤穿透的肿胀行为的MN贴片方面存在挑战。在此，我们报告了由含有ι-卡拉胶、明胶和聚乙二醇的生物聚合物复合材料制成的MN贴片的制备。氯化钙用作交联剂以提高机械强度。对MN贴片的完整性、肿胀行为、机械强度、从琼脂糖凝胶中抽吸液体以及切除的猪耳皮肤进行了表征。在琼脂糖凝胶基质和离体猪皮肤模型中应用后，一组361根微针分别能够抽吸36±5和14±1μL的液体。在体内大鼠模型中应用MN贴片30分钟后，采集到的ISF中葡萄糖、尿酸和促甲状腺激素（TSH）的含量分别为267±128mg/dL、24±13mg/dL和0.6±0.4mIU/mL。同时发现大鼠血液中葡萄糖、尿酸和TSH的浓度分别为199±47mg/dL、8.4±6mg/dL和1.1±0.6mIU/mL。此外，在10名健康人类志愿者的前臂上应用MN贴片30分钟能够抽吸32±14μL的ISF。从人类志愿者的ISF样本中测定的葡萄糖、尿酸和TSH的浓度分别为64±25mg/dL、4.2±4.1mg/dL和0.16±0.08mIU/mL。与皮下注射针头插入相比，应用MN后的视觉模拟评分（VAS）疼痛评分更低。综上所述，可以开发基于生物聚合物复合材料的可膨胀MN贴片，以微创方式采集ISF用于同时测定多种生物分子。
