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

• Published in: European journal of pharmaceutics and biopharmaceutics Vol. 102; pp. 123 - 131
• Main Authors: Eltayib, Eyman, Brady, Aaron J., Caffarel-Salvador, Ester, Gonzalez-Vazquez, Patricia, Zaid Alkilani, Ahlam, McCarthy, Helen O., McElnay, James C., Donnelly, Ryan F.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.05.2016
• Subjects: Administration, Cutaneous; Animals; Drug Delivery Systems - methods; Hydrogel, Polyethylene Glycol Dimethacrylate - administration & dosage; Hydrogel, Polyethylene Glycol Dimethacrylate - chemistry; Lithium; Lithium - administration & dosage; Lithium - chemistry; Male; Microinjections - methods; Microneedles; Needles; Rats; Rats, Sprague-Dawley; Skin - metabolism; Swine; Therapeutic drug monitoring; PBS; MN; OCT; Microneedles; Lithium; PMVE/MA (Gantrez® AN-139); FAAS; N; Therapeutic drug monitoring; SD; PEG; RI; TDM; ISF
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2016.03.009

[Display omitted] 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.