Enhanced neurotrophin-3 bioactivity and release from a nanoparticle-loaded composite hydrogel

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

doi:10.1016/j.jconrel.2012.03.024

Cited by 86 publications

(50 citation statements)

References 47 publications

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“…We found that PDGF-AA was released from the DDS over a period of 21 d, with release primarily occurring in the first 7-10 d. The release profile exhibited a minimal burst release, which is similar to previous studies of NT-3 release from this DDS [26]. These studies also demonstrated that PLGA degradation over the initial 30 d is minimal [26], and we therefore suggest that the rate of release is controlled by diffusion through the wetted nanoparticles and hydrogel.…”

Section: Discussionsupporting

confidence: 88%

“…To this end, we sought to deliver bioactive PDGF-AA from a nanoparticle/hydrogel DDS. We found that the co-encapsulation of PEG400 increased the encapsulation efficiency of PDGF-AA in PLGA nanoparticles, as has been previously reported for NT-3 in PLGA nanoparticles and nerve growth factor (NGF) in PLGA microspheres [20,26]. This is likely due to an increase in viscosity during the primary emulsion, which protects the protein from shear effects.…”

Section: Discussionsupporting

confidence: 84%

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Controlled release of bioactive PDGF-AA from a hydrogel/nanoparticle composite

Donaghue

Shoichet

2015

Acta Biomaterialia

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Previously, the polymer poly(ethylene glycol) (PEG) has been used in many biomaterials applications, from surface coatings to the encapsulation of proteins. In this work, we demonstrate that, unexpectedly, low molecular weight PEG has a deleterious effect on the release of the encapsulated protein platelet-derived growth factor AA (PDGF-AA). We also demonstrate release of bioactive PDGF-AA (in the absence of PEG). Specifically, we demonstrate the differentiation of neural stem and progenitor cells to oligodendrocytes, similar to what is observed with the addition of fresh PDGFAA. A differentiated oligodendrocyte population is a key strategy in central nervous system regeneration. This work is the first demonstration of controlled PDGF-AA release, and also brings new insights to the broader field of protein encapsulation.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionsupporting

confidence: 84%

Controlled release of bioactive PDGF-AA from a hydrogel/nanoparticle composite

Donaghue

Shoichet

2015

Acta Biomaterialia

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“…The GDNF release kinetics and the burst release were much slower when the microspheres were incorporated into the alginate:fibrinogen hydrogel than when they were directly incubated in PBS (Garbayo et al, 2009). This difference can be explained by the hindered diffusion of GDNF across the PLGA-hydrogel boundary (Stanwick et al, 2012), by interactions between the alginate and GDNF, or by slower microsphere degradation. Most likely, a combination of these factors was involved.…”

Section: Discussionmentioning

confidence: 96%

Injectable alginate hydrogel loaded with GDNF promotes functional recovery in a hemisection model of spinal cord injury

Ansorena

Berdt

Ucakar

et al. 2013

International Journal of Pharmaceutics

101

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We hypothesized that local delivery of GDNF in spinal cord lesion via an injectable alginate hydrogel gelifying in situ would support spinal cord plasticity and functional recovery. The GDNF release from the hydrogel was slowed by GDNF encapsulation in microspheres compared to non-formulated GDNF (free GDNF). When injected in a rat spinal cord hemisection model, more neurofilaments were observed in the lesion when the rats were treated with free GDNF-loaded hydrogels. More growing neurites were detected in the tissues surrounding the lesion when the animals were treated with GDNF microsphere-loaded hydrogels. Intense GFAP (astrocytes), low βIII tubulin (neural cells) and RECA-1 (endothelial cells) stainings were observed for non-treated lesions while GDNF-treated spinal cords presented less GFAP staining and more endothelial and nerve fiber infiltration in the lesion site. The animals treated with free GDNF-loaded hydrogel presented superior functional recovery compared with the animals treated with the GDNF microsphere-loaded hydrogels and non-treated animals.

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“…However, as with chondroitinase ABC (chABC), the method of delivery to the spinal cord lesion utilized in many of these studies is not effectively translated to use in humans. Since these factors will be needed for extended periods of time, they can be incorporated into nanoparticles as well as hydrogels or scaffolds for sustained release [Baumann et al, 2010;Stanwick et al, 2012;Kang et al, 2013;des Rieux et al, 2014;Elliott Donaghue et al, 2014. Some of these formulations could potentially function to both stimulate and guide axon regrowth along a specific path though the spinal cord.…”

Section: Nanoparticles As Therapeutics In the Spinal Cordmentioning

confidence: 99%

Nanoparticle Technologies in the Spinal Cord

Zuidema

Gilbert²,

Osterhout

2016

Cells Tissues Organs

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Nanoparticles are increasingly being studied within experimental models of spinal cord injury (SCI). They are used to image cells and tissue, move cells to specific regions of the spinal cord, and deliver therapeutic agents locally. The focus of this article is to provide a brief overview of the different types of nanoparticles being studied for spinal cord applications and present data showing the capability of nanoparticles to deliver the chondroitinase ABC (chABC) enzyme locally following acute SCI in rats. Nanoparticles releasing chABC helped promote axonal regeneration following injury, and the nanoparticles also protected the enzyme from rapid degradation. In summary, nanoparticles are viable materials for diagnostic or therapeutic applications within experimental models of SCI and have potential for future clinical use.

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Enhanced neurotrophin-3 bioactivity and release from a nanoparticle-loaded composite hydrogel

Cited by 86 publications

References 47 publications

Controlled release of bioactive PDGF-AA from a hydrogel/nanoparticle composite

Controlled release of bioactive PDGF-AA from a hydrogel/nanoparticle composite

Injectable alginate hydrogel loaded with GDNF promotes functional recovery in a hemisection model of spinal cord injury

Nanoparticle Technologies in the Spinal Cord

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