The dermal interstitial fluid (ISF) is rich in biomarkers that are of great heuristic value for disease diagnosis and therapeutic drug monitoring. Nevertheless, the current strategies for sampling dermal ISF are both technical and invasive, limiting the potential utility of ISF for clinical medicine and research purposes. In the current work, we present, for the first time, the development, characterization, and evaluation of a novel sorbitol-laced hydrogel-forming microneedles (Sor-Hyd-MN) for sampling dermal ISF. The hydrogel system is fabricated from sorbitol and PEG 10,000 crosslinked with Gantrez® S-97 via esterification in a solvent-free manner. The sorbitol-laced hydrogel rapidly absorbs fluid when placed in aqueous media, reaching a total rise in the mass of 685% relative to the control hydrogel that only reached 436% within 15 mins. When formulated into MNs, the Sor-Hyd-MN exhibited significantly superior (p < 0.001) mechanical properties as evidenced by the minimal MN height reduction (0.9%) relative to the control-MN (3.9%) and Man-Hyd-MN (28.5%) when subjected to a compressive force of 32 N, an analog of patients' thumb pressure. The skin insertion capability of the Sor-Hyd-MN and the control-MN formulation was demonstrated using the in vitro skin simulant, Parafilm® M, and ex vivo neonatal porcine skin. When inserted into ex vivo neonatal porcine skin, the Sor-Hyd-MN showed rapid imbibement of dermal ISF within 15 mins, evidenced via the formation of swollen microchannels, which was 1.2-folds wider than the control formulation. In addition, we also demonstrated for the first time that incorporating sorbitol into Gantrez® S-97 hydrogel-forming MN improved the utility of this formulation in sampling dermal ISF. This was shown from the capability of the Sor-Hyd-MN in extracting the model compounds, isoniazid and theophylline, present within the ISF of ex vivo porcine skin. The Sor-Hyd-MN exhibited an extraction efficiency of 52.4% for isoniazid and 54.4% for theophylline which was significantly higher (p < 0.05) relative to the control formulation in a simple and straightforward manner. This work illustrates that incorporating a hyperosmolyte, such as sorbitol, can further enhance the potential utility of hydrogel-forming MN as a minimally-invasive tool for ISF sampling while providing a potential strategy to extract analytes with ease for subsequent sample analysis.

真皮间质液 (ISF) 富含生物标志物，对疾病诊断和治疗药物监测具有重要启发意义。然而，目前对皮肤 ISF 进行采样的策略既是技术性的又是侵入性的，限制了 ISF 在临床医学和研究目的中的潜在效用。在目前的工作中，我们首次展示了一种新型山梨糖醇水凝胶形成微针 (Sor-Hyd-MN) 的开发、表征和评估，用于对皮肤 ISF 进行采样。水凝胶系统由山梨糖醇和 PEG 10,000 通过 Gantrez® S-97 交联制成以无溶剂方式进行酯化。当置于水性介质中时，含有山梨糖醇的水凝胶迅速吸收液体，相对于在 15 分钟内仅达到 436% 的对照水凝胶，总质量增加了 685%。当配制成 MN 时，Sor-Hyd-MN 表现出显着优越 ( p  < 0.001) 的机械性能，这从相对于对照-MN (3.9%) 和 Man-Hyd-MN ( 28.5%）当受到 32 N 的压缩力时，患者拇指压力的模拟。Sor-Hyd-MN 和对照-MN 制剂的皮肤插入能力已使用体外皮肤模拟物 Parafilm® M 和离体新生猪皮肤进行了证明。当插入离体时在新生猪皮肤中，Sor-Hyd-MN 在 15 分钟内表现出真皮 ISF 的快速吸收，通过形成比对照制剂宽 1.2 倍的膨胀微通道来证明。此外，我们还首次证明，将山梨糖醇加入 Gantrez® S-97 水凝胶形成 MN 可提高该配方在皮肤 ISF 采样中的效用。这从 Sor-Hyd-MN 提取模型化合物异烟肼和茶碱的能力中得到证实，这些化合物存在于离体猪皮肤的 ISF 中。Sor-Hyd-MN 对异烟肼的提取效率为 52.4%，对茶碱的提取效率为 54.4%，明显更高（p < 0.05) 以简单直接的方式相对于对照配方。这项工作表明，加入高渗剂（如山梨糖醇）可以进一步增强形成水凝胶的 MN 作为 ISF 采样的微创工具的潜在效用，同时为后续样品分析提供一种轻松提取分析物的潜在策略。