Preclinical characterization of the efficacy and safety of biologic N-001 as a novel pain analgesic for post-operative acute pain treatment.

Inhibition of actin remodeling in nerves modulates action potential propagation and therefore could be used to treat acute pain. N-001 is a novel protein analgesic engineered from several C. Botulinum toxins. N-001 targets sensory neurons through ganglioside GT1b binding and ADP-ribosylates G-actin reducing actin remodeling. The activity and efficacy of N-001 was evaluated previously in vitro and in a mouse inflammatory pain model. To assess the relevance of N-001 for treatment of acute post-surgical pain, the current study evaluated the efficacy of N-001 in a mouse hind-paw incision model by peri-incisional and popliteal nerve block administration combined with mechanical testing. N-001 provided relief of pain-like behavior over 3 days and 2 days longer than the conventional long-acting anesthetic bupivacaine. Preclinical safety studies of N-001 indicated the drug produced no toxic or adverse immunological reactions over multiple doses in mice. These results combined with past targeting results encourage further investigation of N-001 as an analgesic for post-operative pain management with the potential to function as a differential nociceptor-specific nerve block.

Antimicrobial mechanisms of biomaterials: from macro to nano.

Overcoming the global concern of antibiotic resistance is one of the biggest challenges faced by scientists today, and the key to tackling this issue of emerging infectious diseases is the development of next-generation antimicrobials. The rapid emergence of multi-drug resistant microbes, superbugs and mutated strains of viruses has fuelled the search for new and alternative antimicrobial agents with broad-spectrum biocidal activity. Biomaterials, ranging from macroscopic polymers, proteins, and peptides to nanoscale materials such as nanoparticles, nanotubes and nanosheets have emerged as effective antimicrobials. An extensive body of research has established the antibacterial and antiviral efficiencies of different types of biomaterials. What make these materials unique are the different modes through which they interact and exert their antimicrobial activity. This review provides a comprehensive and detailed overview of the diverse modes of interaction between biomaterials and bacteria and viruses, and sheds light on how different biomaterials influence and modulate antimicrobial mechanisms to achieve a high degree of therapeutic efficacy without resistance generation.