In vitro sustained release of bioactive anti-NogoA, a molecule in clinical development for treatment of spinal cord injury

Stanwick, Jason C.; Baumann, M. Douglas; Shoichet, Molly S.

doi:10.1016/j.ijpharm.2012.01.035

Cited by 33 publications

(8 citation statements)

References 35 publications

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“…In order to achieve a more sustained release for over 7 days, hydrophobic drugs such as FK506 can be dispersed in the solid drug particulate form within the fibrin gel (Wang et al, ). In addition, by incorporating biomaterials such as polymeric microspheres with fibrin gel, various release profiles from weeks to months is possible (Baumann et al, ; Garbayo et al, , ; Stanwick et al, ,; Wood et al, 2013). Poly(lactic‐co‐glycolic acid) (PLGA) is a biocompatible and biodegradable polymer that has been previously used to encapsulate biologically active neurotrophic factors in polymeric microspheres (Garbayo et al, , ; Kokai et al, , ).…”

Section: Introductionmentioning

confidence: 99%

A novel polymeric drug delivery system for localized and sustained release of tacrolimus (FK506)

Tajdaran

Shoichet

Gordon

et al. 2015

Biotech & Bioengineering

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Despite substantial improvement in microsurgical techniques for nerve repair, recovery after peripheral nerve injury is usually incomplete. FK506, an FDA approved immunosuppressant, improves functional recovery and reinnervation following peripheral nerve injury in animal models. However, systemically delivered FK506 causes undesirable global immunosuppression. We have, therefore, engineered a biodegradable local delivery system for FK506 using fibrin gel as a drug reservoir that could be placed at a site of nerve injury. FK506 was incorporated into fibrin gel in solubilized, particulated, and poly(lactic-co-glycolic) acid (PLGA) microspheres-encapsulated forms. A tunable release of FK506 in the fibrin gel from days to weeks was observed with the rate of release being most rapid for the solubilized form and then the particulate form. The most prolonged period of release was seen with the PLGA microsphere-encapsulated form. As analyzed by in vitro dorsal root ganglion (DRG) neurite extension assay, PLGA microsphere encapsulation of FK506 did not alter the drug's properties and the released FK506 maintained its bioactivity over the entire period of release. This study suggests that local delivery of FK506 with fibrin hydrogel could be used to enhance peripheral nerve regeneration.

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Section: Introductionmentioning

confidence: 99%

A novel polymeric drug delivery system for localized and sustained release of tacrolimus (FK506)

Tajdaran

Shoichet

Gordon

et al. 2015

Biotech & Bioengineering

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“…Indeed, the ability to remain localized in situ, together with the possibility of controlling the delivery of hydrophilic high steric hindrance molecules, typical of hydrogels, could be combined with the cell selectivity and with the possibility of tuning the release of hydrophobic drugs, typical role of nanoparticles. Several recent studies have investigated these aspects, trying to combine the advantages of both systems: minocycline [17], methylprednisolone [7], antibodies [18] and growth factors [19] were incorporated in NPs and then loaded into hydrogels to provide a sustained release into the final target tissue, aiming at increasing medical recovery chances. An ideal biomaterial-based delivery platform must achieve localized and sustained release and a favorable risk/benefit ratio to be adopted clinically for SCI treatment.…”

Section: )mentioning

confidence: 99%

Trends in regenerative therapies, combination approaches, and clinical highlights for spinal cord injury (SCI) regeneration

Rossi¹,

Gimona²,

Perale³

2020

Spinal Cord Injury (SCI) Repair Strategies

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As anticipated in the forewords, this book aims at describing the current scenario in spinal cord injury (SCI) regeneration strategies, pointing toward most promising research directions in this wide and complex field. Recent results and clinical achievements from Prof. Courtine's team opened tremendous new directions for restoring patients' functionality, but not by directly regenerating injured tissue, rather by electronically bypassing the lesion gap.Indeed, even if many preclinical studies and promising approaches have been proposed for SCI treatment basing on regenerative purposes, unfortunately nowadays none of them showed relevant efficacy when translated to human patients [1,2]. One of the main reasons is that many cell-based and/or pharmacological approaches are directed only to one specific and single pathway and did not consider combination-based therapies that simultaneously work on neuroprotection (against primary injury) and neuroregeneration of the damaged tissue [3]. Moreover, other problems are strictly related to conventional pharmacological treatments and potential side effects associated. Indeed the most commonly used strategy is represented by continuous infusion by minipumps [4,5]: advantages are associated with immediate drug efficacy and limited side effects. Unfortunately, various drawbacks restrict the applicability of this route of administration, such as limited drug diffusion into the spinal cord segment and cerebrospinal fluid clearance of about 5 h. Higher doses and repeated injections are hence required. Furthermore, problems due to surgery and catheter placement are also frequently reported together with infections [4].Recently, novel engineered biocompatible scaffolds obtained high interest in SCI treatment because they tackle some of the key features of this disease such as the CONCLUSIONS 307Spinal Cord Injury (SCI) Repair Strategies.

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“…Stanwick et al maintained a sustained release of anti-nogoA, a nogoA antagonist that prevents growth cone collapse and demyelination, from PLGA NPs within a HAMC hydrogel. Release occurred over 4 weeks while maintaining bioactivity (Stanwick et al, 2012). To target neurons, oligodendrocytes, and stem cells, sustained growth factor release has been studied in vitro .…”

Section: Biomaterials For Sci and Strategies To Tune The Rate Of Relementioning

confidence: 99%

Biomaterials for Local, Controlled Drug Delivery to the Injured Spinal Cord

Ziemba

Gilbert

2017

Front. Pharmacol.

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Affecting approximately 17,000 new people each year, spinal cord injury (SCI) is a devastating injury that leads to permanent paraplegia or tetraplegia. Current pharmacological approaches are limited in their ability to ameliorate this injury pathophysiology, as many are not delivered locally, for a sustained duration, or at the correct injury time point. With this review, we aim to communicate the importance of combinatorial biomaterial and pharmacological approaches that target certain aspects of the dynamically changing pathophysiology of SCI. After reviewing the pathophysiology timeline, we present experimental biomaterial approaches to provide local sustained doses of drug. In this review, we present studies using a variety of biomaterials, including hydrogels, particles, and fibers/conduits for drug delivery. Subsequently, we discuss how each may be manipulated to optimize drug release during a specific time frame following SCI. Developing polymer biomaterials that can effectively release drug to target specific aspects of SCI pathophysiology will result in more efficacious approaches leading to better regeneration and recovery following SCI.

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In vitro sustained release of bioactive anti-NogoA, a molecule in clinical development for treatment of spinal cord injury

Cited by 33 publications

References 35 publications

A novel polymeric drug delivery system for localized and sustained release of tacrolimus (FK506)

A novel polymeric drug delivery system for localized and sustained release of tacrolimus (FK506)

Trends in regenerative therapies, combination approaches, and clinical highlights for spinal cord injury (SCI) regeneration

Biomaterials for Local, Controlled Drug Delivery to the Injured Spinal Cord

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