Long-Acting Nonopioid Analgesic (LANA) Nanomedicine for Rapid, Single-Dose, Sustained Pain Control and Rehabilitation Support After Neuromusculoskeletal Injury
Abstract
Focus Areas: (1) Pain management strategies following acute and/or chronic neuromusculoskeletal injury that are fast-acting, long-lasting, and free of adverse side effects and (2) solutions to accelerate recovery and restore Warfighter performance in training and operational environments. Peripheral nerve injuries present with a wide range of inter- and intra-patient variabilities due to the state of patient’s health, nature of injury, comorbidities, and location in the body. The immune/nerve cell interactions vary from patient to patient and within the same patient over time following injury and during recovery. We assume and will directly demonstrate that these variabilities are likely directly related to dynamic interactions between the immune and nervous systems in response to injury. Currently, there is no treatment for peripheral nerve injury that would directly engage neuroinflammation at the site of injury as the means of pain treatment and recovery support. To address this, we propose to develop a nanomedicine approach to specifically target the cells involved in the neuroimmune response to peripheral nerve injury. This Long Acting Non-opioid Analgesic (LANA) nanomedicine can accomplish extended pain relief (>72 hours) upon single-low-dose administration and achieve optimal, sustained, stable delivery of non-opioid analgesics to target tissues supporting traumatic neuromusculoskeletal injury recovery and rehabilitation. Targeted drug delivery to these cells will also (1) promote healing of the injured nerve and (2) dramatically minimize drug side effects because injury site-specific delivery improves overall effectiveness of the drug by up to 100-fold. Furthermore, the developed nanomedicine platform will contain imaging agents that will enable tracking of cell migration to and from the site of injury in real time, which will support personalized dosing. Use of imaging agents in animal studies will vastly improve our understanding of the roles immune cells play in peripheral nerve injury associated pain and how they may support recovery and rehabilitation. In Specific Aim 1, we will establish and validate processes for LANA nanomedicine synthesis and formulation development. In Specific Aim 2, we will evaluate safety and establish efficacy of the LANA system in prolonging pain-free outcomes and anti-inflammatory effectiveness in rat injury models. The best candidate nanomedicine will be then, in Specific Aim 3, validated in a non-human primate radial nerve injury model for analgesic efficacy and promoting functional recovery and rehabilitation. Under Specific Aim 4, we will perform scale-up activities of the optimal Nanomedicine Drug Product (LANA) for intravenous administration to support investigational new drug enabling studies. Although not proposed in this application, upon completion of the aims described in this application, the next milestone will be initiation of human clinical studies. The ultimate goal will be to develop a U.S. Food and Drug Administration-approved product for pain management through the continuum from battlefield through rehabilitation. Therefore, the proposed project fits the programmatic goals of Research Level 2—Advancement of laboratory discovery into clinical application and acceleration toward a clinical solution. Ideally, this research will result in the development of a personalized nanomedicine platform that can effectively treat any type of nerve injury in which macrophages and/or Schwann cells play a pivotal role. Imaging agents incorporated into the nanomedicine platform will make it possible to assess the amount of nanomedicine present at the site of injury, thus allowing treatment doses to be tailored to the individual patient. Targeted delivery to the site of injury will lower patient risk of negative side effects. This technology will help both military and civilian populations. It could be used to treat Soldiers that develop nerve injury in r
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010854
Entities
People
- Jelena M. Janjic
Organizations
- Duquesne University
- United States Army