Hydrogel-forming microneedle arrays: Potential for use in minimally-invasive lithium monitoring

详细信息    查看全文

• 作者：Eyman Eltayib^a ; ^b ; Aaron J. Brady^a ; Ester Caffarel-Salvador^a ; Patricia Gonzalez-Vazquez^a ; Ahlam Zaid Alkilani^a ; ^c ; Helen O. McCarthy^a ; James C. McElnay^a ; Ryan F. Donnelly^a ; ^{r.donnelly@qub.ac.uk" class="auth_mail" title="E-mail the corresponding author}
• 关键词：MN ; microneedle (s) ; ISF ; interstitial fluid ; TDM ; therapeutic drug monitoring ; PMVE/MA (Gantrez&reg ; AN-139) ; poly(methylvinylether-co-maelic anhydride) ; PEG ; poly(ethyleneglycol) ; N ; Newtons ; OCT ; optical coherence tomography ; PBS ; phosphate buffered saline ; FAAS ; flame atomic absorption spectrometry ; SD ; Sprague&ndash ; Dawley ; RI ; reverse iontophoresis
• 刊名：European Journal of Pharmaceutics and Biopharmaceutics
• 出版年：2016
• 出版时间：May 2016
• 年：2016
• 卷：102
• 期：Complete
• 页码：123-131
• 全文大小：1570 K

文摘

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 30 min MN application to excised neonatal porcine skin for lithium citrate concentrations of 0.9 and 2 mmol/l. However, after 1 h application, the mean lithium concentrations extracted were significantly different, being appropriately concentration-dependent. In vivo, rats were orally dosed with lithium citrate equivalent to 15 mg/kg and 30 mg/kg lithium carbonate, respectively. MN arrays were applied 1 h after dosing and removed 1 h 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.