Eltayib Eyman, Brady Aaron J, Caffarel-Salvador Ester, Gonzalez-Vazquez Patricia, Zaid Alkilani Ahlam, McCarthy Helen O, McElnay James C, Donnelly Ryan F
School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT97BL, UK; School of Pharmacy, Ahfad University for Women, Arda Street, Omdurman 167, Sudan.
School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT97BL, UK.
Eur J Pharm Biopharm. 2016 May;102:123-31. doi: 10.1016/j.ejpb.2016.03.009. Epub 2016 Mar 9.
We describe, for the first time, hydrogel-forming microneedle (s) (MN) arrays for minimally-invasive extraction and quantification of lithium in vitro and in vivo. MN arrays, prepared from aqueous blends of hydrolysed poly(methyl-vinylether-co-maleic anhydride) and crosslinked by poly(ethyleneglycol), imbibed interstitial fluid (ISF) upon skin insertion. Such MN were always removed intact. In vitro, mean detected lithium concentrations showed no significant difference following 30min MN application to excised neonatal porcine skin for lithium citrate concentrations of 0.9 and 2mmol/l. However, after 1h application, the mean lithium concentrations extracted were significantly different, being appropriately concentration-dependent. In vivo, rats were orally dosed with lithium citrate equivalent to 15mg/kg and 30mg/kg lithium carbonate, respectively. MN arrays were applied 1h after dosing and removed 1h later. The two groups, having received different doses, showed no significant difference between lithium concentrations in serum or MN. However, the higher dosed rats demonstrated a lithium concentration extracted from MN arrays equivalent to a mean increase of 22.5% compared to rats which received the lower dose. Hydrogel-forming MN clearly have potential as a minimally-invasive tool for lithium monitoring in outpatient settings. We will now focus on correlation between serum and MN lithium concentrations.
我们首次描述了用于体外和体内微创提取及定量锂的水凝胶形成微针（MN）阵列。MN阵列由水解聚（甲基乙烯基醚-顺丁烯二酸酐）的水性混合物制备，并通过聚乙二醇交联，插入皮肤后会吸收组织间液（ISF）。此类MN总是完整地被移除。在体外，对于柠檬酸锂浓度为0.9和2mmol/l的情况，将MN应用于切除的新生猪皮肤30分钟后，检测到的平均锂浓度无显著差异。然而，应用1小时后，提取的平均锂浓度存在显著差异，且呈适当的浓度依赖性。在体内，大鼠分别口服相当于15mg/kg和30mg/kg碳酸锂的柠檬酸锂。给药1小时后应用MN阵列，1小时后移除。接受不同剂量的两组大鼠血清或MN中的锂浓度无显著差异。然而，与接受较低剂量的大鼠相比，高剂量组大鼠从MN阵列中提取的锂浓度平均增加了22.5%。水凝胶形成MN显然有潜力作为门诊环境中锂监测的微创工具。我们现在将专注于血清和MN锂浓度之间的相关性。
