Lipid-based microtubular drug delivery vehicles

Meilander, Nancy J.; Yu, Xiaojun; Ziats, Nicholas P.; Bellamkonda, Ravi V.

doi:10.1016/s0168-3659(01)00214-0

Cited by 83 publications

(78 citation statements)

References 34 publications

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“…Our laboratory has previously reported the use of lipid microtubes for the delivery of proteins (27), DNA (28), and neurotrophic factors in vivo (29). Relative to other polyester-based delivery systems, lipid microtubes have the advantage of no protein exposure to heat or organic solvents.…”

Section: Discussionmentioning

confidence: 99%

Sustained delivery of thermostabilized chABC enhances axonal sprouting and functional recovery after spinal cord injury

Lee

McKeon

Bellamkonda

2009

Proc. Natl. Acad. Sci. U.S.A.

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Chondroitin sulfate proteoglycans (CSPGs) are a major class of axon growth inhibitors that are up-regulated after spinal cord injury (SCI) and contribute to regenerative failure. Chondroitinase ABC (chABC) digests glycosaminoglycan chains on CSPGs and can thereby overcome CSPG-mediated inhibition. But chABC loses its enzymatic activity rapidly at 37°C, necessitating the use of repeated injections or local infusions for a period of days to weeks. These infusion systems are invasive, infection-prone, and clinically problematic. To overcome this limitation, we have thermostabilized chABC and developed a system for its sustained local delivery in vivo, obviating the need for chronically implanted catheters and pumps. Thermostabilized chABC remained active at 37°C in vitro for up to 4 weeks. CSPG levels remained low in vivo up to 6 weeks post-SCI when thermostabilized chABC was delivered by a hydrogel-microtube scaffold system. Axonal growth and functional recovery following the sustained local release of thermostabilized chABC versus a single treatment of unstabilized chABC demonstrated significant differences in CSPG digestion. Animals treated with thermostabilized chABC in combination with sustained neurotrophin-3 delivery showed significant improvement in locomotor function and enhanced growth of cholera toxin B subunitpositive sensory axons and sprouting of serotonergic fibers. Therefore, improving chABC thermostability facilitates minimally invasive, sustained, local delivery of chABC that is potentially effective in overcoming CSPG-mediated regenerative failure. Combination therapy with thermostabilized chABC with neurotrophic factors enhances axonal regrowth, sprouting, and functional recovery after SCI.chondroitin sulfate | glial scar | glycosaminoglycans | hydrogel

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Section: Discussionmentioning

confidence: 99%

Sustained delivery of thermostabilized chABC enhances axonal sprouting and functional recovery after spinal cord injury

Lee

McKeon

Bellamkonda

2009

Proc. Natl. Acad. Sci. U.S.A.

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281

243

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“…LMTs-A drug delivery system using LMTs of 1,2-bis (tricosa-10,12-diyomoyl)-sn-3-phosphocholine (DC8,9PC; Avanti Polar Lipids, Inc., Alabster, AL) was prepared by ethanol deposition method, and used for slow-release of NGF, as described in other studies [30,42]. The LMTs had an average length of 45±20 μm ( Figure 1).…”

Section: Ngf Release From Ngf-loadedmentioning

confidence: 99%

“…LMTs can also be easily embedded in agarose scaffolds facilitating slow-release of trophic factors, without physically impeding the growth cones that navigate the scaffolds. By controlling the amount of protein loaded into the microtubules, the number of microtubules used, and the length of microtubules; it is possible to control the duration of release of protein and the amount of protein released [42]. In this study we have used LMTs for slow-release of NGF, and by loading different amounts of LMTs in different parts of the scaffold; we created NGF gradients to promote axonal regeneration.…”

Section: Introductionmentioning

confidence: 99%

Differences between the effect of anisotropic and isotropic laminin and nerve growth factor presenting scaffolds on nerve regeneration across long peripheral nerve gaps

2008

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Anisotropic scaffolds of agarose hydrogels containing gradients of laminin-1 (LN-1) and nerve growth factor (NGF) molecules were used to promote sciatic nerve regeneration across a challenging 20 mm nerve gap in rats.Step and continuous gradient anisotropic scaffolds were fabricated and characterized and regeneration was compared to that in isotropic scaffolds with uniform concentrations of LN-1 and NGF and sciatic nerve grafts harvested from syngenic rats. Polysulfone tubular guidance channels were used to present the agarose based scaffolds to the nerve stumps. Fourmonths after implantation, regenerating axons were observed in animals implanted with anisotropic scaffolds with gradients of both LN-1 and NGF molecules and nerve grafts, but not in animals with isotropic scaffold implants. Also, the scaffolds with gradient of either LN-1 or NGF, with the other component being uniformly distributed in the scaffold, did not elicit axonal regeneration. The total number of myelinated axons was similar for the anisotropic scaffold and the nerve graft conditions, with the anisotropic scaffolds having a higher density of axons than the nerve grafts. Axonal diameter distribution was similar for the anisotropic scaffolds and the nerve grafts. The nerve grafts and anisotropic scaffolds resulted in better functional outcome compared to isotropic scaffolds as measured by the relative gastrocnemius muscle weight (RGMW). Additionally the state of neuromuscular junctions as assessed by pre-and post-synaptic staining revealed that both the anistropic scaffolds performed as well as nerve grafts.

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“…Differentiated cells were defined as those with neurites longer than the soma diameter [20]. Most of the PC12 cells were differentiated in RPMI 1640 complete medium with 50 ng/mL NGF (Figure 1(a)) and in the extract of NGF-embedded composites (Figure 1(c)).…”

Section: Resultsmentioning

confidence: 99%

Degradable PRGD/PDLLA/β-TCP/NGF composites promote differentiation and regulate gene expression in rat pheochromocytoma cells

Qiu

Yan

et al. 2013

Chin. Sci. Bull.

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In this study, we synthesized degradable PRGD/PDLLA/-TCP/NGF composites to facilitate neuronal repair. To this end, we (1) examined the release of nerve growth factor (NGF) from the composites, (2) evaluated the differentiation status of the cells and (3) address how transcriptional activity may regulate the differentiation mechanism of these cells. NGF content was determined using enzyme-linked immunosorbent assay, while the cellular mRNA expression was examined by real-time PCR analysis. Our results indicated that NGF release was robust during the first 10 days and then stabilized at a lower level thereafter. Treatment of PC12 cells with the extract of the NGF-embedded composites induced the formation of neurites and, in some cases, net-like neurites. Analysis of the expression level of differentiation-related genes, such as TrkA, VGF, Rab1, GAP43 and β-tubulin II, were significantly up-regulated. These findings suggest that these composites might be a suitable delivery system for growth factors like NGF that can be used to facilitate neuronal repair after injury.nerve guidance conduit, nerve growth factor, neuronal repair, PC12 cells Citation:Qiu T, Yu C, Yan Q J, et al. Degradable PRGD/PDLLA/-TCP/NGF composites promote differentiation and regulate gene expression in rat pheochromocytoma cells.

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Lipid-based microtubular drug delivery vehicles

Cited by 83 publications

References 34 publications

Sustained delivery of thermostabilized chABC enhances axonal sprouting and functional recovery after spinal cord injury

Sustained delivery of thermostabilized chABC enhances axonal sprouting and functional recovery after spinal cord injury

Differences between the effect of anisotropic and isotropic laminin and nerve growth factor presenting scaffolds on nerve regeneration across long peripheral nerve gaps

Degradable PRGD/PDLLA/β-TCP/NGF composites promote differentiation and regulate gene expression in rat pheochromocytoma cells

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