Thermosensitive biomaterial gels with chemical permeation enhancers for enhanced microneedle delivery of naltrexone for managing opioid and alcohol dependency.

Naltrexone (NTX) can be transdermally delivered using microneedles (MN) to treat opioid and alcohol misuse disorders, but delivery is blunted by rapid micropore closure. Poloxamer (P407), a thermosensitive biocompatible hydrogel, sustains NTX delivery through MN-treated skin by generating a drug depot within the micropores. Optimizing P407 formulations could maintain sustained delivery after micropore closure while reducing required patch sizes, which would be more discreet and preferred by most patients.

Thermosensitive Gels Used to Improve Microneedle-Assisted Transdermal Delivery of Naltrexone.

Transdermal delivery of naltrexone (NTX) can be enhanced using microneedles, although micropores generated this way can reseal by 48 h in humans, which prevents further drug delivery from a formulation. Poloxamer 407 (P407) is a thermosensitive polymer that may extend microneedle-assisted NTX delivery time by creating an in situ gel depot in the skin. We characterized gelation temperature, drug release, and permeation of P407 gels containing 7% NTX-HCl.

Ca-Binding Protein 1 Regulates Hippocampal-dependent Memory and Synaptic Plasticity.

Ca-binding protein 1 (CaBP1) is a Ca-sensing protein similar to calmodulin that potently regulates voltage-gated Ca channels. Unlike calmodulin, however, CaBP1 is mainly expressed in neuronal cell-types and enriched in the hippocampus, where its function is unknown. Here, we investigated the role of CaBP1 in hippocampal-dependent behaviors using mice lacking expression of CaBP1 (C-KO).

CaBP1 regulates Ca1 L-type Ca channels and their coupling to neurite growth and gene transcription in mouse spiral ganglion neurons.

CaBP1 is a Ca binding protein that is widely expressed in neurons in the brain, retina, and cochlea. In heterologous expression systems, CaBP1 interacts with and regulates voltage-gated Ca Ca channels but whether this is the case in neurons is unknown. Here, we investigated the cellular functions of CaBP1 in cochlear spiral ganglion neurons (SGNs), which express high levels of CaBP1.

Suppression of Resting Metabolism by the Angiotensin AT2 Receptor.

Activation of the brain renin-angiotensin system (RAS) stimulates energy expenditure through increasing of the resting metabolic rate (RMR), and this effect requires simultaneous suppression of the circulating and/or adipose RAS. To identify the mechanism by which the peripheral RAS opposes RMR control by the brain RAS, we examined mice with transgenic activation of the brain RAS (sRA mice). sRA mice exhibit increased RMR through increased energy flux in the inguinal adipose tissue, and this effect is attenuated by angiotensin II type 2 receptor (AT2) activation.