Nano PGE1 promoted the recovery from spinal cord injury-induced motor dysfunction through its accumulation and sustained release

Takenaga, Mitsuko; Ishihara, Tsutomu; Ohta, Yuki; Tokura, Yukie; Hamaguchi, Akemi; Igarashi, Rie; Mizushima, Tohru

doi:10.1016/j.jconrel.2010.08.003

Cited by 18 publications

(13 citation statements)

References 30 publications

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“…C2 released sustainedly from the nanoparticles by using high molecular weight PLA, which is useful in clinic. Mitsuko Takenaga et al (20) focused on the effect of Nano PGE1on SCI-induced motor dysfunction in a rat model and examined its distribution and the mechanism. The results suggested that nano PGE1 significantly improved hind limb motor dysfunction induced by SCI in rats.…”

Section: Discussionmentioning

confidence: 99%

“…A number of new alternative dosage forms of PGE1, such as lipid microspheres (15), inhaled PLGA particles (16)(17)(18) for pulmonary arterial hypertension, and nanoparticles (19)(20)(21)(22), can prevent PGE1 from inactivation in blood and improve the efficacy of PGE1. Among these new dosage forms, PGE1 lipid microspheres (lipo-PGE1) were established by Mizushima (15).…”

Section: Introductionmentioning

confidence: 99%

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Development, Optimization, and Characterization of PEGylated Nanoemulsion of Prostaglandin E1 for Long Circulation

Cheng

Liu

Hu³

et al. 2015

AAPS PharmSciTech

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Abstract. Lipo-PGE1 is the most widely used formulation of PGE1 in clinic. However, PGE1 is easier to leak out from lipo-PGE1 and this will lead to the phlebophlogosis when intravenous injection. The stability of lipo-PGE1 in storage and in vivo is also discounted. The aim of this study is to develop a long-circulating prostaglandin E1-loaded nanoemulsion modified with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG) to improve the stability and pharmacokinetics profiles of lipo-PGE1. PEGylated PGE1 nanoemulsion was prepared using a dispersing-homogenized method. The stability of nanoemulsion in 1 month was investigated. Pharmacokinetic studies were employed to evaluate the in vivo profile of the optimized nanoemulsion. The optimized nanoemulsion PGE1-PEG2000(1%)-NE showed an oil droplet size <100 nm with a surface charge of −14 mV. Approximately, 97% of the PGE1 was encapsulated in the nanoemulsion. The particle size, zeta potential, and drug loading of PGE1-PEG2000(1%)-NE were stable in 1 month. After PGE1-PEG2000(1%)-NE was intravenously administered to rats, the area under curve (AUC) and half-life of PGE1 were, respectively, 1.47-fold and 5.98-fold higher than those of lipo-PGE1 (commercial formulation). PGE1-PEG2000(1%)-NE was an ideal formulation for prolonging the elimination time of PGE1. This novel parenteral colloidal delivery system of PGE1 has a promising potential in clinic use.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Development, Optimization, and Characterization of PEGylated Nanoemulsion of Prostaglandin E1 for Long Circulation

Cheng

Liu

Hu³

et al. 2015

AAPS PharmSciTech

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“…97,136,137 Como na prática clínica as nanoemulsões são frequentemente diluídas em outros fluidos para a administração, resultando em alterações no efeito farmacológico esperado, 96,97,138 diversos pesquisadores têm estudado modificações na formulação, 133,138 ou desenvolvido novos sistemas carreadores (nanopartículas poliméricas). 139 A substituição da PGE1 por seu pró-fármaco AS013 resultou em maior estabilidade química do fármaco na emulsão e, assim, em um efeito mais prolongado. 133,140 Outras nanoemulsões de PGE1 contendo óleo de oliva como núcleo oleoso também já estão disponíveis comercialmente no Japão (Alyprost ® , Nippon Chemiphar, e Prink ® , Taiyo Yakuhin).…”

Section: Prostaglandina Eunclassified

Nanoemulsões como sistemas de liberação parenteral de fármacos

Bruxel¹,

Laux²,

Wild³

et al. 2012

Quím. Nova

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Recebido em 20/10/11; aceito em 29/3/12; publicado na web em 3/7/12 NANOEMULSIONS AS PARENTERAL DRUG DELIVERY SYSTEMS. Lipid nanoemulsions have recently been proposed as parenteral delivery systems for poorly-soluble drugs. These systems consist of nanoscale oil/water dispersions stabilized by an appropriate surfactant system in which the drug is incorporated into the oil core and/or adsorbed at the interface. This article reviews technological aspects of such nanosystems, including their composition, preparation methods, and physicochemical properties. From this review, it was possible to identify five groups of nanoemulsions based on their composition. Biopharmaceutical aspects of formulations containing some commercially available drugs (diazepam, propofol, dexamethasone, etomidate, flurbiprofen and prostaglandin E1) were then discussed.Keywords: emulsion; parenteral; drug. INTRODUÇÃOA solubilização de fármacos de reduzida hidrossolubilidade visando sua administração parenteral representa um grande desafio na área de desenvolvimento de medicamentos. Diversas estratégias são descritas na literatura para esta finalidade, incluindo a modificação do pH do veículo, a adição de cossolventes ou, ainda, a formação de complexos de inclusão com ciclodextrinas.1 Entretanto, limitações relacionadas à biocompatibilidade dos adjuvantes empregados, aos relatos de dor e de possível precipitação dos fármacos durante a administração podem ser considerados como fatores limitantes do uso destas abordagens. Neste contexto, sistemas nanoestruturados têm se mostrado promissores. Nanoemulsões lipídicas óleo em água têm sido empregadas há mais de 40 anos como fonte de calorias e ácidos graxos essenciais 2 e, mais recentemente, como sistemas de liberação de fármacos. A biocompatibilidade das matérias-primas empregadas para a sua obtenção (óleos de origem natural ou semissintética e fosfolipídeos) torna estes sistemas uma alternativa promissora para a administração de diversos tipos de moléculas.3 Nanoemulsões podem ser definidas como sistemas heterogêneos nos quais um líquido (a fase interna) é disperso em outro (a fase externa) na forma de gotículas, na presença de um agente emulsionante. Suas propriedades físico--químicas, influenciadas pela composição quali-e quantitativa e pelas condições de preparação, devem ser estritamente controladas, visando a administração por via parenteral e a estabilidade do sistema. 4,5 Existem na literatura algumas inconsistências relacionadas aos conceitos de nanoemulsões em relação às microemulsões. Apesar destes sistemas poderem apresentar características estruturais e visuais semelhantes em determinadas condições, diferenciam-se quanto a estabilidade termodinâmica. Contrariamente às nanoemulsões, as microemulsões são sistemas termodinamicamente estáveis. Entretanto, podem apresentar limitações para administração por via parenteral, pois suas propriedades são fortemente afetadas por alterações de temperatura e/ou diluições. Apesar da nomenclatura empregada, microemulsões apresentam geralmente tamanho...

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“…Nano PGE1 prevents inactivation of PGE1 and the particles accumulate at target sites where PGE1 release occurs along with degradation of the polymer. Nano PGE1 has been demonstrated to show therapeutic potential for spinal cord injury in rats [8], and also increases the activity of rats with intermittent claudication [9]. These reports suggested to us that Nano PGE1 could also be effective for peripheral nerve injury.…”

Section: Introductionmentioning

confidence: 75%

“…This might be partly explained by differences of the drug release profile. PGE1 is released slowly from nanoparticles and there is little initial burst effect, while PGE1 is released rapidly from lipid microspheres at the target site [8].…”

Section: Discussionmentioning

confidence: 99%

Nano PGE1 Enhances Phosphorylation of ERK1/2 and Akt to Promote Recovery from Motor Dysfunction and Muscle Atrophy Induced by Sciatic Nerve Injury

Takenaga¹,

Ishihara²,

Niimi³

et al. 2019

Preprint

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The effect of prostaglandin E1 (PGE1) encapsulated in nanoparticles (Nano PGE1) on motor dysfunction and muscle atrophy induced by sciatic nerve injury (SNI) was investigated in rats, and was compared with PGE1 encapsulated in lipid microspheres (Lipo PGE1) or PGE1 clathrated in cyclodextrin (PGE1-CD). The hind limb muscle weight ratio decreased until 2 weeks after SNI. All 3 PGE1 formulations significantly improved SNI-induced motor dysfunction. Nano PGE1 significantly promoted recovery from muscle atrophy at 2 and 3 weeks after SNI. Lipo PGE1 was also effective, but multiple doses were required. Compared with the SNI control group, the Nano PGE1 group showed upregulation of vascular endothelial growth factor (VEGF) and agrin expression in the injured sciatic nerve and atrophic muscles. Nano PGE1 accumulated prominently at the site of nerve injury and persisted for longer than Lipo PGE1 or PGE1-CD. Expression of all EP receptors was detected in the normal sciatic nerve, and EP2 expression increased after SNI. Finally, Nano PGE1 promoted ERK1/2 and Akt phosphorylation. These findings suggest that PGE1 released from nanoparticles accumulates at sites of nerve injury and increases VEGF production by augmenting ERK1/2 phosphorylation via EP receptor signaling, thus promoting tissue repair and regeneration.

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Nano PGE1 promoted the recovery from spinal cord injury-induced motor dysfunction through its accumulation and sustained release

Cited by 18 publications

References 30 publications

Development, Optimization, and Characterization of PEGylated Nanoemulsion of Prostaglandin E1 for Long Circulation

Development, Optimization, and Characterization of PEGylated Nanoemulsion of Prostaglandin E1 for Long Circulation

Nanoemulsões como sistemas de liberação parenteral de fármacos

Nano PGE1 Enhances Phosphorylation of ERK1/2 and Akt to Promote Recovery from Motor Dysfunction and Muscle Atrophy Induced by Sciatic Nerve Injury

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