Hydrogel-forming microneedle arrays made from light-responsive materials for on-demand transdermal drug delivery

We describe, for the first time, stimuli-responsive hydrogel-forming microneedle (MN) arrays that enable delivery of a clinically-relevant model drug (ibuprofen) upon application of light. MN arrays were prepared using a polymer prepared from 2-hydroxyethyl methacrylate (HEMA) and ethylene glycol dimethacrylate (EGDMA) by micromolding. The obtained MN arrays showed good mechanical properties. The system was loaded with up to 5% (w/w) ibuprofen included in a light-responsive 3,5-dimethoxybenzoin conjugate. Raman spectroscopy confirmed the presence of the conjugate inside the polymeric MN matrix. In vitro, this system was able to deliver up to three doses of 50 mg of ibuprofen upon application of an optical trigger over a prolonged period of time (up to 160 hours). This makes the system appealing as a controlled release device for prolonged periods of time. We believe that this technology has potential for use in ?on-demand? delivery of a wide range of drugs in a variety of applications relevant to enhanced patient care.

Functional expression of thermo-sensitive TRP channels in human odontoblasts

Introduction: Accumulating evidence supports a role for odontoblasts in initiating tooth pain, however direct ionic mechanisms underlying dentine nociceptive function remain unclear. The transient receptor potential (TRP) ion channels are directly related to cellular mechanisms of nociception and thermo-sensitive function but their expression by human odontoblasts remains to be determined. Objectives: To investigate the expression and functionality of the thermo-sensitive TRP channels TRPV1, TRPV4, TRPM8 and TRPA1 in human odontoblasts. Methods: Human odontoblasts were derived from dental pulp of immature permanent third molars by explant method. Cell lysates of odontoblasts were subject to SDS- polyacrylamide gel electrophoresis and proteins were blotted onto nitrocellulose membranes. Blots were probed with primary antibodies to TRPA1, TRPM8, TRPV4 and TRPV1. Detection of bound primary antibodies was achieved using appropriate anti-species antibody conjugates and chemiluminescent substrates. Functionality of the channels was determined with Ca2+ microfluorimetry, where cells grown in cover slips and incubated with Fura 2AM prior to stimulation with capsaicin (TRPV1 agonist), 4 alpha-phorbol 12,13-didecanoate (4áPDD) (TRPV4 agonist), icilin (TRPA1 agonist) and menthol (TRPM8 agonist). Emitted fluorescence was measured and the fluorescence ratio (R) was calculated as F340/F380 to determine the level of [Ca2+]i. Results: Western blotting confirmed the molecular localisation of thermo-sensitive TRP channels in human odontoblasts. Functionality assays revealed increase in [Ca2+]i in response to capsacin, icillin, methanol and 4áPDD indicating functional expression of TRPV1, TRPA1, TRPM8 and TRPV4 respectively. Conclusions: Functional expression of thermo-sensitive TRP channels in human odontoblasts may indicate a crucial role for odontoblasts in thermally induced dental pain. (Supported by a Research Grant from the Royal College of Surgeons of Edinburgh)