Brain biocompatibility of a biodegradable, controlled‐release polymer in rats

Tamargo, Rafael J.; Epstein, Jonathan I.; Reinhard, Carla S.; Chasin, Mark; Brem, Henry

doi:10.1002/jbm.820230209

Cited by 148 publications

(53 citation statements)

References 10 publications

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“…There has been interest for several decades in using drug delivery technologies to affect neuronal function locally, in the central (40) and peripheral nervous systems (31), particularly in the development of prolonged duration local anesthetics. A wide range of devices have been used for the latter application (24,26,27,30,(41)(42)(43)(44)(45).…”

Section: Discussionmentioning

confidence: 99%

Prolonged nerve blockade delays the onset of neuropathic pain

Shankarappa

Tsui

Kim

et al. 2012

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

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Aberrant neuronal activity in injured peripheral nerves is believed to be an important factor in the development of neuropathic pain. Pharmacological blockade of that activity has been shown to mitigate the onset of associated molecular events in the nervous system. However, results in preventing onset of pain behaviors by providing prolonged nerve blockade have been mixed. Furthermore, the experimental techniques used to date to provide that blockade were limited in clinical potential in that they would require surgical implantation. To address these issues, we have used liposomes (SDLs) containing saxitoxin (STX), a site 1 sodium channel blocker, and the glucocorticoid agonist dexamethasone to provide nerve blocks lasting ∼1 wk from a single injection. This formulation is easily injected percutaneously. Animals undergoing spared nerve injury (SNI) developed mechanical allodynia in 1 wk; nerve blockade with a single dose of SDLs (duration of block 6.9 ± 1.2 d) delayed the onset of allodynia by 2 d. Treatment with three sequential SDL injections resulting in a nerve block duration of 18.1 ± 3.4 d delayed the onset of allodynia by 1 mo. This very prolonged blockade decreased activation of astrocytes in the lumbar dorsal horn of the spinal cord due to SNI. Changes in expression of injury-related genes due to SNI in the dorsal root ganglia were not affected by SDLs. These findings suggest that formulations of this kind, which could be easy to apply clinically, can mitigate the development of neuropathic pain.

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Section: Discussionmentioning

confidence: 99%

Prolonged nerve blockade delays the onset of neuropathic pain

Shankarappa

Tsui

Kim

et al. 2012

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

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“…31 Currently, polymers engaged in clinical trials, poly[bis(p-carboxyphenoxy)propane-sebacic acid] and poly(D,L-lactide-co-glycolide), are degraded totally in vivo in 5-8 weeks. [32][33][34] In a biocompatibility study that was performed by our group, PPM 2.1.2-based microspheres were perfectly intact after 3 months in the rat brain (unpublished data). Therefore, the microsphere method seems to have promise, and we believe in the possibility of developing a method for the long release of drug into the brain, thus avoiding repetitive stereotactic injections.…”

Section: Discussion Polymers For Drug Delivery To the Cnsmentioning

confidence: 92%

Therapeutic effectiveness of novel 5‐fluorouracil‐loaded poly(methylidene malonate 2.1.2)‐based microspheres on F98 glioma‐bearing rats

Fournier¹,

Passirani²,

Montero‐Menei³

et al. 2003

Cancer

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BACKGROUNDDrug delivery to the central nervous system (CNS) remains a real challenge for neurosurgeons and neurologists, because many molecules cannot cross the blood‐brain barrier (BBB). In recent years, solid polymeric materials have been implanted into animal and human brains either by surgery or using stereotactic methods to assure the controlled release of a drug over a determined period, thus circumventing the difficulties posed by the BBB. Poly(methylidene malonate 2.1.2) (PMM 2.1.2) is a new polymer that was described a few years ago and that allows the fabrication of novel, 5‐fluorouracil (5‐FU)‐loaded PMM 2.1.2 microspheres. The objective of the current study was to assess the therapeutic effectiveness of those particles in a rat brain tumor model, the F98 glioma.METHODSForty‐three rats were used in this study. First, a histologic evaluation of the F98 tumor model was performed on Fischer female rats. Thereafter, different groups of rats were injected and were treated with 5‐FU microspheres in 2 different suspension media: carboxymethylcellulose (CMC) aqueous solution with or without 5‐FU.RESULTSThe tumor was confirmed as extremely aggressive and invasive, even in early development. The 5‐FU‐loaded microspheres improved rat median survival significantly compared with untreated animals, CMC‐treated animals, and 5‐FU solution‐treated animals when injected in CMC without 5‐FU, demonstrating the interest of a sustained release and the efficacy of intratumoral chemotherapy against an established tumor.CONCLUSIONSPMM 2.1.2 microspheres appeared to be a promising system, because their degradation rate in vivo was longer compared with many polymers, and they may be capable of long‐term delivery. Cancer 2003;97:2822–9. © 2003 American Cancer Society.DOI 10.1002/cncr.11388

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“…O seu interesse tem aumentado nos últimos anos, uma vez que são não mutagênicos, não citotóxicos e não teratogênicos [62,63] . Foi ainda demonstrada a sua biocompatibilidade e biodegradabilidade no cérebro [64,65] . Sistemas de polianídridos alifáticos têm sido desenvolvidos para a liberação modificada de princípios ativos a nível parenteral [66] .…”

Section: Polianidridos Alifáticosunclassified

Polímeros usados como sistemas de transporte de princípios ativos

Severino¹,

Santana

Malmonge

et al. 2011

Polímeros

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Resumo: Os diferentes sistemas de transporte têm evidenciado potencial terapêutico para uma grande variedade de princípios ativos, satisfazendo vários requisitos, como a prevenção da sua eliminação rápida do organismo, a redução da sua toxicidade sistêmica, a estabilização e a otimização do seu metabolismo, e o direcionamento específico ao local alvo e os mecanismos de defesa. No entanto, têm sido reconhecidos vários outros desafios associados à liberação específica do princípio ativo ao local alvo, pelo que, para ultrapassar os obstáculos químicos e biológicos, a seleção do polímero utilizado para a preparação do sistema de transporte é de importância crucial. O presente trabalho apresenta um relato sobre os principais polímeros naturais e sintéticos utilizados para a preparação de sistemas de transporte de princípios ativos in vivo. Palavras-chaves: Polímeros sintéticos, polímeros naturais, transporte de princípios ativos. Polymers for Drug Delivery Systems FormulationsAbstract: The different carrier systems have shown therapeutic potential for a wide variety of drugs, satisfying multiple requirements, such as prevention of rapid elimination, reducing toxicity, promoting stabilization, optimization of metabolism, drug delivery and defense mechanisms. However, it has been recognized several other challenges associated with the specific release of actives in drug delivery. Therefore, to overcome chemical and biological obstacles, the selection of the polymer used to prepare the transport system is crucial. This paper presents a report on the main natural and synthetic polymers used in the preparation of drug carrier systems in vivo. Keywords: Synthetic polymers, natural polymers, carrier of drugs. IntroduçãoA investigação científica de novos meios de veiculação de princípios ativos in vivo permitiu o desenvolvimento de vários tipos de sistemas de transporte dos quais se destacam os lipossomas [1] , conjugados de polímero e princípios ativos [2] , micelas de copolímeros anfipáticos [3] , micro e nanopartículas poliméricas [4] e, mais recentemente, as nanopartículas lipídicas sólidas [5] . Os diferentes sistemas de transporte têm evidenciado potencial terapêutico para uma grande variedade de princípios ativos, preenchendo assim vários requisitos, como a prevenção da sua eliminação rápida do organismo [6] , a redução da sua toxicidade sistêmica [7] , a estabilização e a otimização do seu metabolismo [8] , o direcionamento específico ao local alvo [9] e os mecanismos de defesa [10] . No entanto, têm sido reconhecidos vários outros desafios associados à liberação específica do princípio ativo ao local alvo, pelo que, para ultrapassar os obstáculos químicos e biológicos, a seleção do polímero utilizado para a preparação do sistema de transporte é de importância crucial.Para a preparação dos sistemas poliméricos de transporte, pode recorrer-se ao uso de polímeros naturais [11] , sintéticos [12] ou semi-sintéticos [13] . A seleção do polímero a ser empregado está condicionada, em grande medida pela natureza do princípio...

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Brain biocompatibility of a biodegradable, controlled‐release polymer in rats

Cited by 148 publications

References 10 publications

Prolonged nerve blockade delays the onset of neuropathic pain

Prolonged nerve blockade delays the onset of neuropathic pain

Therapeutic effectiveness of novel 5‐fluorouracil‐loaded poly(methylidene malonate 2.1.2)‐based microspheres on F98 glioma‐bearing rats

Polímeros usados como sistemas de transporte de princípios ativos

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