Abstract
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.
Highlights
Despite the introduction of a wide range of mood stabilizing agents, lithium is still considered the ‘gold standard’ treatment for bipolar (BP) disorder [1,2]
This study demonstrates, for the first time, the potential of hydrogel-forming MN as a means of transdermal lithium therapeutic drug monitoring (TDM) using interstitial fluid (ISF) as a sampling reservoir
We have successfully demonstrated hydrogel-forming MN have the potential as a means of minimally-invasive lithium TDM
Summary
Despite the introduction of a wide range of mood stabilizing agents, lithium is still considered the ‘gold standard’ treatment for bipolar (BP) disorder [1,2]. Lithium is a cornerstone of neuropsychopharmacology, primarily used to treat BP affective disorder, where it can improve both manic and depressive symptoms [3]. It has many off-label uses, including treatment of alcoholism, hyperthyroidism, personality disorders, traumatic brain injury, tardive dyskinesia and Abbreviations: MN, microneedle (s); ISF, interstitial fluid; TDM, therapeutic drug monitoring; PMVE/MA (GantrezÒ 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–Dawley; RI, reverse iontophoresis. Like all alkali metals, is highly reactive [5] It readily forms, and can be administered as, salts such as citrate, sulphate, chloride and, most commonly, carbonate. These salts are available in several different dosage forms, such as syrup and both conventional and sustained release tablets and capsules [4,6]
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