Co-delivery of minocycline and paclitaxel from injectable hydrogel for treatment of spinal cord injury

Nazemi, Zahra; Nourbakhsh, Mohammad Sadegh; Kiani, Sahar; Heydari, Yasaman; Ashtiani, Mohammad Kazemi; Daemi, Hamed; Baharvand, Hossein

doi:10.1016/j.jconrel.2020.02.009

Cited by 77 publications

(45 citation statements)

References 74 publications

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“…In addition, rats on the dual-drug regimen had reduced scar tissue and increased neuronal regeneration after 28 days. Over time, the animals receiving the dual-drug regimen showed rapid and sustained improvement in function compared with other groups (Nazemi et al, 2020). Taxol was added to electrospinning poly(Llactic acid) (PLLA) microfibers, and it was confirmed that taxol released from well-arranged electrospinning microfibers promoted neurite extension in growth-friendly and growthinhibiting environments (Roman et al, 2016).…”

Section: Polymer Scaffolds Small Molecule Drugs Composite Platformmentioning

confidence: 95%

Polymer-Based Scaffold Strategies for Spinal Cord Repair and Regeneration

Chen

Shu

et al. 2020

Front. Bioeng. Biotechnol.

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The injury to the spinal cord is among the most complex fields of medical development. Spinal cord injury (SCI) leads to acute loss of motor and sensory function beneath the injury level and is linked to a dismal prognosis. Currently, while a strategy that could heal the injured spinal cord remains unforeseen, the latest advancements in polymer-mediated approaches demonstrate promising treatment forms to remyelinate or regenerate the axons and to integrate new neural cells in the SCI. Moreover, they possess the capacity to locally deliver synergistic cells, growth factors (GFs) therapies and bioactive substances, which play a critical role in neuroprotection and neuroregeneration. Here, we provide an extensive overview of the SCI characteristics, the pathophysiology of SCI, and strategies and challenges for the treatment of SCI in a review. This review highlights the recent encouraging applications of polymer-based scaffolds in developing the novel SCI therapy.

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Section: Polymer Scaffolds Small Molecule Drugs Composite Platformmentioning

confidence: 95%

Polymer-Based Scaffold Strategies for Spinal Cord Repair and Regeneration

Chen

Shu

et al. 2020

Front. Bioeng. Biotechnol.

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“…Generally, spinal cord injury includes a series of events, such as vascular changes, free radical formation, the disruption of ionic balance, apoptosis, and inflammatory responses are triggered by spinal cord injury. Considering post-surgery local treatment of spinal injury, Nazemi et al administrated, a combination of neuroprotective drug, minocycline hydrochloride (MH) and neurodegenerative drug, paclitaxel (PTX) into the lesion site of a hemi-section model of spinal cord injury in rats at acute phase [145]. An affinity injectable alginate hydrogel, based on electrostatic interactions, and metal-ion chelation that incorporated MH, a water-soluble small molecule drug, was developed for this purpose.…”

Section: Spinal Cord Injury Treatmentmentioning

confidence: 99%

“…Subsequently, PTX was encapsulated in the PLGA microspheres and inserted in the alginate hydrogel ( Figure 7A). They demonstrated that the dual-drug treatment was capable of reducing inflammation, enhancing neurogenesis, and promoting functional recovery [145].…”

Section: Spinal Cord Injury Treatmentmentioning

confidence: 99%

“…(A) Spinal cord injury treatment using alginate hydrogel preparation encapsulated with multi-drug loaded PLGA particles for injection into the lesion site. Adapted with permission from Nazemi et al[145]. (B) Localized administration of vortex-domain iron oxide-functionalized magnetic hydrogel for breast cancer postoperative recurrence prevention using its pH-responsivity.…”

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confidence: 99%

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Stimuli-Responsive Hydrogels for Local Post-Surgical Drug Delivery

Askari

Seyfoori

Amereh

et al. 2020

Gels

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Currently, surgical operations, followed by systemic drug delivery, are the prevailing treatment modality for most diseases, including cancers and trauma-based injuries. Although effective to some extent, the side effects of surgery include inflammation, pain, a lower rate of tissue regeneration, disease recurrence, and the non-specific toxicity of chemotherapies, which remain significant clinical challenges. The localized delivery of therapeutics has recently emerged as an alternative to systemic therapy, which not only allows the delivery of higher doses of therapeutic agents to the surgical site, but also enables overcoming post-surgical complications, such as infections, inflammations, and pain. Due to the limitations of the current drug delivery systems, and an increasing clinical need for disease-specific drug release systems, hydrogels have attracted considerable interest, due to their unique properties, including a high capacity for drug loading, as well as a sustained release profile. Hydrogels can be used as local drug performance carriers as a means for diminishing the side effects of current systemic drug delivery methods and are suitable for the majority of surgery-based injuries. This work summarizes recent advances in hydrogel-based drug delivery systems (DDSs), including formulations such as implantable, injectable, and sprayable hydrogels, with a particular emphasis on stimuli-responsive materials. Moreover, clinical applications and future opportunities for this type of post-surgery treatment are also highlighted.

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“…In recent decades, hydrogels have been developed as delivery systems for proregenerative agents to promote neural tissue regeneration after SCI (Hassannejad et al, 2019;Ma et al, 2020;Nazemi et al, 2020). According to several studies, synthetic SAP hydrogels have been designed and form nanofiber scaffolds in vivo under physiological conditions (Ahuja and Fehlings, 2016;Koss and Unsworth, 2016;Hong et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Local Delivery of Taxol From FGL-Functionalized Self-Assembling Peptide Nanofiber Scaffold Promotes Recovery After Spinal Cord Injury

Xiao

Yao

Wang

et al. 2020

Front. Cell Dev. Biol.

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Taxol has been clinically approved as an antitumor drug, and it exerts its antitumor effect through the excessive stabilization of microtubules in cancer cells. Recently, moderate microtubule stabilization by Taxol has been shown to efficiently promote neurite regeneration and functional recovery after spinal cord injury (SCI). However, the potential for the clinical translation of Taxol in treating SCI is limited by its side effects and low ability to cross the blood-spinal cord barrier (BSCB). Self-assembled peptide hydrogels have shown potential as drug carriers for the local delivery of therapeutic agents. We therefore hypothesized that the localized delivery of Taxol by a self-assembled peptide scaffold would promote axonal regeneration by stabilizing microtubules during the treatment of SCI. In the present study, the mechanistic functions of the Taxol-releasing system were clarified in vitro and in vivo using immunofluorescence labeling, histology and neurobehavioral analyses. Based on the findings from the in vitro study, Taxol released from a biological functionalized SAP nanofiber scaffold (FGLmx/Taxol) remained active and promoted neurite extension. In this study, we used a weight-drop contusion model to induce SCI at T9. The local delivery of Taxol from FGLmx/Taxol significantly decreased glial scarring and increased the number of nerve fibers compared with the use of FGLmx and 5% glucose. Furthermore, animals administered FGLmx/Taxol exhibited neurite preservation, smaller cavity dimensions, and decreased inflammation and demyelination. Thus, the local delivery of Taxol from FGLmx/Taxol was effective at promoting recovery after SCI and has potential as a new therapeutic strategy for SCI.

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Co-delivery of minocycline and paclitaxel from injectable hydrogel for treatment of spinal cord injury

Cited by 77 publications

References 74 publications

Polymer-Based Scaffold Strategies for Spinal Cord Repair and Regeneration

Polymer-Based Scaffold Strategies for Spinal Cord Repair and Regeneration

Stimuli-Responsive Hydrogels for Local Post-Surgical Drug Delivery

Local Delivery of Taxol From FGL-Functionalized Self-Assembling Peptide Nanofiber Scaffold Promotes Recovery After Spinal Cord Injury

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