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Nanomedicine in cerebral palsy.

Balakrishnan B, Nance E, Johnston MV, Kannan R, Kannan S - Int J Nanomedicine (2013)

Bottom Line: Nanomaterials such as dendrimers provide opportunities for the targeted delivery of multiple drugs that can mitigate several pathways involved in injury and can be delivered specifically to the cells that are responsible for neuroinflammation and injury.These materials also offer the opportunity to deliver agents that would promote repair and regeneration in the brain, resulting not only in attenuation of injury, but also enabling normal growth.Future directions that would facilitate clinical translation in neonates and children are also addressed.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University; Baltimore, MD, USA.

ABSTRACT
Cerebral palsy is a chronic childhood disorder that can have diverse etiologies. Injury to the developing brain that occurs either in utero or soon after birth can result in the motor, sensory, and cognitive deficits seen in cerebral palsy. Although the etiologies for cerebral palsy are variable, neuroinflammation plays a key role in the pathophysiology of the brain injury irrespective of the etiology. Currently, there is no effective cure for cerebral palsy. Nanomedicine offers a new frontier in the development of therapies for prevention and treatment of brain injury resulting in cerebral palsy. Nanomaterials such as dendrimers provide opportunities for the targeted delivery of multiple drugs that can mitigate several pathways involved in injury and can be delivered specifically to the cells that are responsible for neuroinflammation and injury. These materials also offer the opportunity to deliver agents that would promote repair and regeneration in the brain, resulting not only in attenuation of injury, but also enabling normal growth. In this review, the current advances in nanotechnology for treatment of brain injury are discussed with specific relevance to cerebral palsy. Future directions that would facilitate clinical translation in neonates and children are also addressed.

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Schematic of dendrimer.
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f1-ijn-8-4183: Schematic of dendrimer.

Mentions: Dendrimers, soft globular molecules about 3–10 nm in size, are emerging as promising candidates for diagnostic platforms and targeted drug and gene delivery vehicles (Figure 1). Recently, promising efficacy results have been reported in preclinical studies, including cancer, systemic inflammation and rheumatoid arthritis.45–48 The small size, branching architecture, and high density of tailorable surface functional groups can provide significant advantages for CNS and BBB transport. Polyamidoamine (PAMAM) dendrimers are widely studied due to their commercial availability. The growing interest in the PAMAM dendrimer as a vehicle for drugs is mainly attributable to the ability of the nanoparticle to enhance the selectivity and stability of the drug. In vivo administration of PAMAM dendrimer grafts attached to the anticancer drug 5-fluorouracil (5-FU) in rats has shown to increase its bioavailability compared with the free drug.49 The efficacy of nonsteroidal anti-inflammatory drugs such as indomethacin has been shown to be enhanced by conjugation of the drug with folic acid-coupled dendrimers in a rat model of arthritis.50 Cell-specific internalization of a dendrimer-drug conjugate has been reported to overcome the resistant action of P-glycoprotein in tumor cells. Kukowska-Latallo et al51 have reported that when acetylated dendrimer conjugated with folic acid and coupled with methotrexate was injected into immunodeficient mice bearing tumor cells, there was increased uptake of drug into tumor-specific cells. Poly(ethylene glycol)-lysine dendrimers have been used as a carrier to deliver nitric oxide to alleviate the symptoms of atherosclerosis.52 Recent studies by Iezzi et al and Kannan et al have shown that hydroxyl-functionalized PAMAM dendrimers can target neuroinflammation in the retina upon intravitreal administration and provide sustained neuroprotection for at least 30 days through targeted, intracellular delivery of a steroid.39


Nanomedicine in cerebral palsy.

Balakrishnan B, Nance E, Johnston MV, Kannan R, Kannan S - Int J Nanomedicine (2013)

Schematic of dendrimer.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3818020&req=5

f1-ijn-8-4183: Schematic of dendrimer.
Mentions: Dendrimers, soft globular molecules about 3–10 nm in size, are emerging as promising candidates for diagnostic platforms and targeted drug and gene delivery vehicles (Figure 1). Recently, promising efficacy results have been reported in preclinical studies, including cancer, systemic inflammation and rheumatoid arthritis.45–48 The small size, branching architecture, and high density of tailorable surface functional groups can provide significant advantages for CNS and BBB transport. Polyamidoamine (PAMAM) dendrimers are widely studied due to their commercial availability. The growing interest in the PAMAM dendrimer as a vehicle for drugs is mainly attributable to the ability of the nanoparticle to enhance the selectivity and stability of the drug. In vivo administration of PAMAM dendrimer grafts attached to the anticancer drug 5-fluorouracil (5-FU) in rats has shown to increase its bioavailability compared with the free drug.49 The efficacy of nonsteroidal anti-inflammatory drugs such as indomethacin has been shown to be enhanced by conjugation of the drug with folic acid-coupled dendrimers in a rat model of arthritis.50 Cell-specific internalization of a dendrimer-drug conjugate has been reported to overcome the resistant action of P-glycoprotein in tumor cells. Kukowska-Latallo et al51 have reported that when acetylated dendrimer conjugated with folic acid and coupled with methotrexate was injected into immunodeficient mice bearing tumor cells, there was increased uptake of drug into tumor-specific cells. Poly(ethylene glycol)-lysine dendrimers have been used as a carrier to deliver nitric oxide to alleviate the symptoms of atherosclerosis.52 Recent studies by Iezzi et al and Kannan et al have shown that hydroxyl-functionalized PAMAM dendrimers can target neuroinflammation in the retina upon intravitreal administration and provide sustained neuroprotection for at least 30 days through targeted, intracellular delivery of a steroid.39

Bottom Line: Nanomaterials such as dendrimers provide opportunities for the targeted delivery of multiple drugs that can mitigate several pathways involved in injury and can be delivered specifically to the cells that are responsible for neuroinflammation and injury.These materials also offer the opportunity to deliver agents that would promote repair and regeneration in the brain, resulting not only in attenuation of injury, but also enabling normal growth.Future directions that would facilitate clinical translation in neonates and children are also addressed.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University; Baltimore, MD, USA.

ABSTRACT
Cerebral palsy is a chronic childhood disorder that can have diverse etiologies. Injury to the developing brain that occurs either in utero or soon after birth can result in the motor, sensory, and cognitive deficits seen in cerebral palsy. Although the etiologies for cerebral palsy are variable, neuroinflammation plays a key role in the pathophysiology of the brain injury irrespective of the etiology. Currently, there is no effective cure for cerebral palsy. Nanomedicine offers a new frontier in the development of therapies for prevention and treatment of brain injury resulting in cerebral palsy. Nanomaterials such as dendrimers provide opportunities for the targeted delivery of multiple drugs that can mitigate several pathways involved in injury and can be delivered specifically to the cells that are responsible for neuroinflammation and injury. These materials also offer the opportunity to deliver agents that would promote repair and regeneration in the brain, resulting not only in attenuation of injury, but also enabling normal growth. In this review, the current advances in nanotechnology for treatment of brain injury are discussed with specific relevance to cerebral palsy. Future directions that would facilitate clinical translation in neonates and children are also addressed.

Show MeSH
Related in: MedlinePlus