Synthesis of Poly (Carboxyphenoxypropane-Sebacic Anhydride) for the Delivery of Drugs to the Brain

Domb, Abraham J.; Kubek, Michael J.

doi:10.1007/978-1-4615-0579-2_27

Cited by 1 publication

(3 citation statements)

References 12 publications

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“…Methods developed to deliver neuropeptides via liposomes and capsular carriers have not been effective. 16,32,[58][59][60] Early sustained-release formulations of TRH-containing Copoly((ϩ)-lactic/glycolic acid) (PLGA) microspheres injected subcutaneously caused a dose-dependent shortening of pentobarbitone-induced sleeping time 61 and improved experimentally induced parkinsonism 62 in rats, but at levels known to stimulate an unwanted endocrine response. Therefore, sustained-release preparations loaded with neuropeptides in combination with the advantages obtained from intranasal delivery may provide the key elements for attaining more prolonged, site-specific effects while reducing unwanted side effects.…”

Section: Effect Of Intranasal Delivery Of Trh Nanoparticles On Kindlimentioning

confidence: 99%

“…64 Our D,L-polylactide nanoparticles are submicronsized (ϳ100 nm) polymeric colloidal particles, with a therapeutic agent of interest (i.e., TRH) entrapped within their polymeric matrix. [58][59][60] The use of TRH-NPs is hypothesized to increase target tissue bioavailability after intranasal delivery.…”

Section: Effect Of Intranasal Delivery Of Trh Nanoparticles On Kindlimentioning

confidence: 99%

“…73 Similar to other, smaller neuropeptides, TRH is a relatively stable compound that can be incorporated into polymeric devices in varying concentrations with minimal loss of bioactivity by proteolytic enzymes. 58,60,74 The actual kinetics of TRH release from the nanoparticles has not been characterized in vivo. Future work in this area should provide insight into TRH site distribution, rates of degradation, and long-term receptor modulation.…”

Section: Nanoparticle Characteristicsmentioning

confidence: 99%

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Attenuation of Kindled Seizures by Intranasal Delivery of Neuropeptide-Loaded Nanoparticles

2009

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Summary: Thyrotropin-releasing hormone (TRH; Protirelin), an endogenous neuropeptide, is known to have anticonvulsant effects in animal seizure models and certain intractable epileptic patients. Its duration of action, however, is limited by rapid tissue metabolism and the blood-brain barrier. Direct nose-tobrain delivery of neuropeptides in sustained-release biodegradable nanoparticles (NPs) is a promising mode of therapy for enhancing CNS neuropeptide bioavailability. To provide proof of principle for this delivery approach, we used the kindling model of temporal lobe epilepsy to show that 1) TRH-loaded copolymer microdisks implanted in a seizure focus can attenuate kindling development in terms of behavioral stage, afterdischarge duration (ADD), and clonus duration; 2) intranasal administration of an unprotected TRH analog can acutely suppress fully kindled seizures in a concentration-dependent manner in terms of ADD and seizure stage; and 3) intranasal administration of polylactide nanoparticles (PLA-NPs) containing TRH (TRH-NPs) can impede kindling development in terms of behavioral stage, ADD, and clonus duration. Additionally, we used intranasal delivery of fluorescent dye-loaded PLA-NPs in rats and application of dye-loaded or dye-attached NPs to cortical neurons in culture to demonstrate NP uptake and distribution over time in vivo and in vitro respectively. Also, a nanoparticle immunostaining method was developed as a procedure for directly visualizing the tissue level and distribution of neuropeptide-loaded nanoparticles. Collectively, the data provide proof of concept for intranasal delivery of TRH-NPs as a viable means to 1) suppress seizures and perhaps epileptogenesis and 2) become the lead compound for intranasal anticonvulsant nanoparticle therapeutics.

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Section: Effect Of Intranasal Delivery Of Trh Nanoparticles On Kindlimentioning

confidence: 99%

Section: Effect Of Intranasal Delivery Of Trh Nanoparticles On Kindlimentioning

confidence: 99%

Section: Nanoparticle Characteristicsmentioning

confidence: 99%

See 1 more Smart Citation

Attenuation of Kindled Seizures by Intranasal Delivery of Neuropeptide-Loaded Nanoparticles

2009

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Synthesis of Poly (Carboxyphenoxypropane-Sebacic Anhydride) for the Delivery of Drugs to the Brain

Cited by 1 publication

References 12 publications

Attenuation of Kindled Seizures by Intranasal Delivery of Neuropeptide-Loaded Nanoparticles

Attenuation of Kindled Seizures by Intranasal Delivery of Neuropeptide-Loaded Nanoparticles

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