The use of supramolecular systems in biomedical applications for antimicrobial properties, biocompatibility, and drug delivery.

Supramolecular chemistry is versatile for developing stimuli-responsive, dynamic and multifunctional structures. In the context of biomedical engineering applications, supramolecular assemblies are particularly useful as coatings for they can closely mimic the natural structure and organisation of the extracellular matrix (ECM), they can also fabricate other complex systems like drug delivery systems and bioinks. In the current context of growing medical device-associated complications and the developments in the controlled drug delivery and regenerative medicine fields, supramolecular assemblies are becoming an indispensable part of the biomedical engineering arsenal. This review covers the different supramolecular assemblies in different biomedical applications with a specific focus on antimicrobial coatings, coatings that enhance biocompatibility, surface modifications on implantable medical devices, systems that promote therapeutic efficiency in cancer therapy, and the development of bioinks. The introduced supramolecular systems include multilayer coating by polyelectrolytes, polymers incorporated with nanoparticles, coating simulation of ECM, and drug delivery systems. A perspective on the application of supramolecular systems is also included.

Action of mefloquine/amitriptyline THN101 combination on neuropathic mechanical hypersensitivity in mice.

ABSTRACT: Tricyclic antidepressants that inhibit serotonin and noradrenaline reuptake, such as amitriptyline, are among the first-line treatments for neuropathic pain, which is caused by a lesion or disease affecting the somatosensory nervous system. These treatments are, however, partially efficient to alleviate neuropathic pain symptoms, and better treatments are still highly required. Interactions between neurons and glial cells participate in neuropathic pain processes, and importantly, connexins-transmembrane proteins involved in cell-cell communication-contribute to these interactions. In a neuropathic pain model in rats, mefloquine, a connexin inhibitor, has been shown to potentiate the antihyperalgesic effect of amitriptyline, a widely used antidepressant. In this study, we further investigated this improvement of amitriptyline action by mefloquine, using the cuff model of neuropathic pain in mice. We first observed that oral mefloquine co-treatment prolonged the effect of amitriptyline on mechanical hypersensitivity by 12 hours after administration. In addition, we showed that this potentiation was not due to pharmacokinetic interactions between the 2 drugs. Besides, lesional and pharmacological approaches showed that the prolonged effect was induced through noradrenergic descending pathways and the recruitment of α2 adrenoceptors. Another connexin blocker, carbenoxolone, also improved amitriptyline action. Additional in vitro studies suggested that mefloquine may also directly act on serotonin transporters and on adenosine A1 and A2A receptors, but drugs acting on these other targets failed to amplify amitriptyline action. Together, our data indicate that pharmacological blockade of connexins potentiates the therapeutic effect of amitriptyline in neuropathic pain.

Phenylpyridine-2-ylguanidines and rigid mimetics as novel inhibitors of TNFα overproduction: Beneficial action in models of neuropathic pain and of acute lung inflammation.

4-phenylpyridin-2-yl-guanidine (5b): a new inhibitor of the overproduction of pro-inflammatory cytokines (TNFα and Il1ß) was identified from a high-throughput screening of a chemical library on human peripheral blood mononuclear cells (PBMCs) after LPS stimulation. Derivatives, homologues and rigid mimetics of 5b were designed and synthesized, and their cytotoxicity and ability to inhibit TNFα overproduction were evaluated. Among them, compound 5b and its mimetic 12 (2-aminodihydroquinazoline) showed similar inhibitory activities, and were evaluated in vivo in models of lung inflammation and neuropathic pain in mice. In particular, compound 12 proved to be active (5 mg/kg, ip) in both models.