Current strategies for therapeutic drug delivery after traumatic CNS injury.
Lee Hyun Joon,Ryu Jung Su,Vig Parminder Js
Therapeutic delivery
Therapeutic strategies for traumatic injuries in the central nervous system (CNS) are largely limited to the efficiency of drug delivery. Despite the disrupted blood-CNS barrier during the early phase after injury, the drug administration faces a variety of obstacles derived from homeostatic imbalance at the injury site. In the late phase after CNS injury, the restoration of the blood-CNS barrier integrity varies depending on the injury severity resulting in inconsistent delivery of therapeutics. This review intends to characterize those different challenges of the therapeutic delivery in acute and chronic phases after injury and discuss recent advances in various approaches to explore novel strategies for the treatment of traumatic CNS injury.
10.4155/tde-2019-0006
Emerging molecular therapeutic targets for spinal cord injury.
Wang Shuo,Smith George M,Selzer Michael E,Li Shuxin
Expert opinion on therapeutic targets
: Spinal cord injury (SCI) is a complicated and devastating neurological disorder. Patients with SCI usually have dramatically reduced quality of life. In recent years, numerous studies have reported advances in understanding the pathophysiology of SCI and developing preclinical therapeutic strategies for SCI, including various molecular therapies, and yet there is still no cure. : After SCI, tissue damage, responses and repair involve interactions among many cellular components, including neurons, axons, glia, leukocytes, and other cells. Accordingly, numerous cellular genes and molecules have become therapeutic targets for neural tissue repair, circuit reconstruction, and behavioral restoration. Here, we review the major recent advances in biological and molecular strategies to enhance neuroprotection, axon regeneration, remyelination, neuroplasticity and functional recovery in preclinical studies of SCI. : Researchers have made tremendous progress in identifying individual and combined molecular therapies in animal studies. It is very important to identify additional highly effective treatments for early neuroprotective intervention and for functionally meaningful axon regeneration and neuronal reconnections. Because multiple mechanisms contribute to the functional loss after SCI, combining the most promising approaches that target different pathophysiological and molecular mechanisms should exhibit synergistic actions for maximal functional restoration. [Databases searched: PubMed; inclusive dates: 6/27/2019].
10.1080/14728222.2019.1661381
Drug delivery, cell-based therapies, and tissue engineering approaches for spinal cord injury.
Kabu Shushi,Gao Yue,Kwon Brian K,Labhasetwar Vinod
Journal of controlled release : official journal of the Controlled Release Society
Spinal cord injury (SCI) results in devastating neurological and pathological consequences, causing major dysfunction to the motor, sensory, and autonomic systems. The primary traumatic injury to the spinal cord triggers a cascade of acute and chronic degenerative events, leading to further secondary injury. Many therapeutic strategies have been developed to potentially intervene in these progressive neurodegenerative events and minimize secondary damage to the spinal cord. Additionally, significant efforts have been directed toward regenerative therapies that may facilitate neuronal repair and establish connectivity across the injury site. Despite the promise that these approaches have shown in preclinical animal models of SCI, challenges with respect to successful clinical translation still remain. The factors that could have contributed to failure include important biologic and physiologic differences between the preclinical models and the human condition, study designs that do not mirror clinical reality, discrepancies in dosing and the timing of therapeutic interventions, and dose-limiting toxicity. With a better understanding of the pathobiology of events following acute SCI, developing integrated approaches aimed at preventing secondary damage and also facilitating neuroregenerative recovery is possible and hopefully will lead to effective treatments for this devastating injury. The focus of this review is to highlight the progress that has been made in drug therapies and delivery systems, and also cell-based and tissue engineering approaches for SCI.
10.1016/j.jconrel.2015.08.060
Nanovector-mediated drug delivery for spinal cord injury treatment.
Caron Ilaria,Papa Simonetta,Rossi Filippo,Forloni Gianluigi,Veglianese Pietro
Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology
Spinal cord injury (SCI) is the result of a traumatic primary event followed by a so-called secondary injury, which is characterized by a large spectrum of biochemical cellular pathways able to spread the lesion, worsening neurologic recovery. A growing number of potential therapeutic interventions to counteract different neurodegenerative mechanisms of SCI have been proposed, but they did not show relevant efficacy when translated as clinical treatments. Different reasons could explain these disappointing results: on one side the multifactorial evolution of SCI after the primary injury that limits the beneficial effect of just one targeted treatment and, on the other, the restricted access of pharmacological therapies to the spinal cord. For these reasons, recently, a growing interest has been shown in the development of alternative delivery strategies to administer drugs and/or biological/cellular therapies into the spine (hydrogel and nanoparticles).
10.1002/wnan.1276